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Study Objectives This is a Phase 2, multicenter, open-label, multi-cohort study to assess safety and efficacy of CC-90011 in combination with nivolumab in subjects with small cell lung cancer or squamous non-small cell lung cancer who have progressed after 1 or 2 lines of therapies. The primary objectives of the study are to evaluate the overall response rate of subjects treated with CC-90011 in combination with nivolumab in three cohorts: * Cohort A: SCLC in ICI naïve subjects * Cohort B: SCLC in ICI progressor subjects * Cohort C: sqNSCLC in ICI progressor subjects Overall response rate is defined as the proportion of subjects in the treated population who had complete response (CR) or partial response (PR) as assessed by Investigator review per RECIST v1.1. In Cohort A, expected ORR for nivolumab monotherapy is 14% while target ORR is 30%. To achieve at least 80% power with one-sided type 1 error 0.1, 39 subjects will be enrolled according to a 2-stage group sequential design based on a binomial test. In stage 1, 12 subjects will be enrolled and treated with CC-90011 in combination with nivolumab. If there are 2 or more subjects responding, Cohort A will continue to enroll an additional 27 subjects. If 1 or less subjects respond in stage 1, Cohort A will stop for futility. In Cohort B and C, expected ORR for nivolumab monotherapy is 5% while target ORR is 15%. To achieve at least 80% power with one-sided type 1 error 0.1, 48 subjects will be enrolled according to a 2-stage group sequential design based on a binomial test. In stage 1, 14 subjects will be enrolled and treated with CC-90011 in combination with nivolumab. If there are 1 or more subjects responding, Cohort B and C will continue to enroll an additional 34 subjects each. If 0 subjects respond in stage 1, Cohort B and C will stop for futility. Conditions: Neoplasms Intervention / Treatment: DRUG: CC-90011, DRUG: Nivolumab Location: Italy, Spain, United Kingdom, United States, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: * Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF). * Subject with histological or cytological confirmation of extensive stage Small Cell Lung Cancer (ES SCLC) or Stage IIIb or IV squamous Non-Small Cell Lung Cancer (sqNSCLC) * Subject has received 1 or 2 prior lines of therapies, defined as: 1. Cohort A (SCLC, Immune Checkpoint Inhibitor naïve): * At least 1 prior treatment including a platinum-based chemotherapy doublet * A minimum of 3 cycles of platinum-based chemotherapy in first line treatment, unless stopped at 2 cycles due to treatment-related toxicity 2. Cohort B (SCLC, ICI progressors): * At least 1 prior first or second line treatment includes an ICI * If treatment includes an ICI as maintenance therapy, at least 1 cycle of ICI in maintenance should have been completed * At least 1 prior treatment including a platinum-based chemotherapy doublet * A minimum of 3 cycles of platinum-based chemotherapy, with or without ICI, in first line treatment, unless stopped at 2 cycles due to treatment-related toxicity * Subject must have progressed during ICI therapy, defined as unequivocal progression on or within 3 months of the last dose of ICI therapy (if no subsequent therapy) 3. Cohort C (sqNSCLC, ICI progressors): * At least 1 prior first or second line treatment includes an ICI * If treatment includes an ICI as maintenance therapy, at least 1 cycle of ICI in maintenance should have been completed * At least 1 prior treatment including a platinum-based chemotherapy doublet * A minimum of 3 cycles of platinum-based chemotherapy, with or without an ICI, in first line treatment, unless stopped at 2 cycles due to treatment-related toxicity * Subject must have progressed during ICI therapy, defined as unequivocal progression on or within 3 months of the last dose of ICI therapy (if no subsequent therapy) * Subject has progressed at the last line of therapy. * Subject has a measurable disease defined by RECIST v1.1. * Subject agrees to provide a tumor biopsy from primary or metastatic site prior to first dose and at a pre-specified timepoint during treatment. Core biopsy is required however, in the event a core biopsy may not otherwise be feasible in the opinion of the treating physician, an endobronchial ultrasound-guided fine needle aspirate \[EBUS-FNA\]) biopsy, using the largest gauge needle, may be performed instead. * Subject has ECOG Performance Status of 0 to 1. * Subject must have the following laboratory values: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 2. Hemoglobin (Hgb) ≥ 9 g/dL (one-time blood transfusion is allowed) 3. Platelet (Plt) Count ≥ 150 x 109/L 4. White blood cells (WBC) ≥ 2 x 109L 5. Serum AST/serum glutamic oxaloacetic transaminase (SGOT) or ALT/serum glutamic pyruvic transaminase (SGPT) ≤ 3 x upper limit of normal (ULN) or ≤ 5 x ULN if presence of liver metastases 6. Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN, if Gilbert's syndrome or if indirect bilirubin concentrations are suggestive of extrahepatic source of the elevation) 7. Creatinine clearance (CrCl) ≥ 60 mL/minute based on Cockcroft-Gault or modification of diet in renal disease (MDRD) or ≥ 60 mL/min/1.73 m2 Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: * Subject has not recovered to Grade 2 or lower clinically significant toxicities related to the prior therapy (alopecia excluded). * Subject has received prior LSD1 therapies. * Subject has a history of severe hypersensitivity reactions to other monoclonal antibodies * Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases. 1. Subject has recently been treated with whole brain radiation or stereotactic radiosurgery for CNS metastases must have completed therapy at least 2 weeks prior to Cycle 1 Day 1 and has a follow-up brain computed tomography (CT) or magnetic resonance imaging (MRI) demonstrating either stable or improving metastases 2 or more weeks after completion of radiotherapy. 2. Subject must be asymptomatic and off steroids or on stable dose of steroids for at least 2 weeks (≤ 10 mg daily prednisone or equivalent) prior to first dose. * Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant gastrointestinal (GI) disorder that could affect the absorption of the study treatments. * Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages. * Subject with any hemorrhage/bleeding event > NCI CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose. * Subject has any of the following cardiovascular criteria: 1. Evidence of acute or ongoing cardiac ischemia 2. Current symptomatic pulmonary embolism 3. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to enrollment 4. Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to enrollment 5. Persistent or clinically meaningful ventricular arrhythmias prior to enrollment 6. Cerebral vascular accident or transient ischemic attack ≤ 6 months prior to enrollment 7. QT corrected based on Fridericia's equation (QTcF) ≥ 450 milliseconds (msec) on Screening ECG, a baseline prolongation of QTcF interval ≥ 450 msec (NCI CTCAE Grade ≥ 2) 8. A history of additional risk factors for Torsades de pointes (TdP) (eg, heart failure, hypokalemia, family history of Long QT Syndrome) 9. Uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg) * Subject has known human immunodeficiency virus (HIV) infection. * Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection. 1. Subject who is seropositive due to HBV vaccination is eligible. 2. Subject who has no active viral infection and is under adequate prophylaxis against HBV reactivation is eligible. * Subject has any other malignancy within 2 years prior to enrollment, with the exception of adequately treated in-situ bladder cancer, in-situ carcinoma of the cervix, uteri, nonmelanomatous skin cancer, ductal in situ breast carcinoma, thyroid cancer, or early stage prostate cancer (all treatment of which should have been completed 6 months prior to enrollment). * Subject has medical conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. 1. A brief (≤ 7 days) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted. 2. Adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease. 3. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted. * Subject has active autoimmune diseases or history of autoimmune diseases that may relapse. Subjects with the following diseases are allowed to be enrolled after further screening: type I diabetes, hypothyroidism managed with hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia), or diseases not expected to recur in the absence of external triggering factors. * Subject is pregnant or nursing. * Subject has a history of persistent skin rash ≥ NCI CTCAE Grade 2 related to prior ICI therapy. * Subject has organ transplant history, including allogeneic stem cell transplant. * Subject has interstitial lung disease history. * Subject has received a live/attenuated vaccine within 30 days of first dose. * Subject has previous SARS-CoV-2 infection either suspected or confirmed within 4 weeks prior to screening. 1. Acute symptoms must have resolved and based on Investigator assessment in consultation with the Medical Monitor, there are no sequelae that would place the subject at a higher risk of receiving investigational treatment.

Study Objectives This is a single-arm, multicenter, Phase 2 study of lenvatinib in combination with everolimus in participants with unresectable advanced or metastatic non clear cell renal cell carcinoma (nccRCC) who have not received any chemotherapy for advanced disease. The primary objective of the study is to evaluate the objective response rate (ORR). This study consists of three phases: a Pretreatment Phase (Screening and Baseline Periods), a Treatment Phase (starting Cycle 1, Day 1), and a Posttreatment Phase (End of Treatment Visit and survival Follow-up). Conditions: Non Clear Cell Renal Cell Carcinoma (nccRCC) Intervention / Treatment: DRUG: lenvatinib, DRUG: everolimus Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Males or females age ≥18 years at the time of informed consent form (ICF) * Participants with histologically confirmed non clear cell renal cell carcinoma (nccRCC) who have not received any chemotherapy for advanced disease. Participants must have one of the following subtypes of nccRCC: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified. * Radiologically measurable disease meeting the following criteria: 1. At least 1 lesion of ≥10 millimeters (mm) in the longest diameter for a nonlymph node or ≥15 mm in the short axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computerized tomography (CT) or magnetic resonance imaging (MRI); 2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of subsequent progressive disease (substantial size increase of ≥20%) to be deemed a target lesion. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Blood pressure (BP) ≤140/90 millimeters of mercury (mmHg) at Screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1. * Adequate renal function as evidenced by calculated creatinine clearance ≥30 milliliters (mL)/minute according to the Cockcroft and Gault formula * Adequate bone marrow function: 1. Absolute neutrophil count (ANC) ≥1.5 × 10\^9/liter (L); 2. Hemoglobin ≥10.0 grams per deciliter (g/dL) (can be corrected by growth factor or transfusion prior to first dose of study drug); 3. Platelet count ≥100 × 10\^9/L * Adequate liver function: 1. Bilirubin ≤1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome; 2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if participant has liver metastases). If ALP is >3 × ULN (in the absence of liver metastases) or >5 × ULN (in the presence of liver metastases) AND participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP. * Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol Exclusion Criteria: * Predominant clear cell renal cell carcinoma (RCC) * Prior anticancer chemotherapy or targeted therapy for advanced nccRCC * Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor * Known intolerance to lenvatinib, everolimus (or other rapamycin derivatives), or any of the excipients * Major surgery performed within 3 weeks prior to the first dose of study drugs or scheduled for major surgery during the study * Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib or everolimus * Participants having >1+ proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 grams (g)/24 hours will be ineligible. * Fasting total cholesterol ˃300 milligrams (mg)/dL (or ˃7.75 millimoles \[mmol\]/L) or fasting triglycerides level ˃2.5 × ULN. Note: these participants can be included after initiation or adjustment of lipid-lowering medication. * Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: In case this threshold is exceeded, these participants can only be included after initiation or adjustment of glucose-lowering medication. * Known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis. * Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II; (b) unstable angina; (c) myocardial infarction; (d) stroke; or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs * Prolongation of QTcF interval to >480 milliseconds (msec) * Known history of human immunodeficiency virus (HIV) positive * Known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] RNA detected) * Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug * Participants with central nervous system (CNS) (e.g., brain or leptomeningeal) metastases. * Other active malignancy (except definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months * Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[β-hCG\] or human chorionic gonadotropin \[hCG\] test with a minimum sensitivity of 25 International Units \[IU\]/L or equivalent units of β-hCG or hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. * Females of childbearing potential who: 1. Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method \[such as a condom plus diaphragm with spermicide\], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 28 days after study drug discontinuation 2. Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from being sexually active during the study period or for 28 days after study drug discontinuation 3. Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation 4. Are using oral hormonal contraceptives and who do not agree to add a barrier method * Note: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). * Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period and for 28 days after study drug discontinuation. * Evidence of clinically significant disease (e.g., cardiovascular, respiratory, gastrointestinal, renal, or infectious disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments * Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study * Active and current use of illegal recreational drugs * Currently enrolled in another interventional clinical study or used any investigational drug or device within the past 28 days preceding informed consent

Study Objectives This is a phase 1 trial designed to evaluate safety and tolerability of chemotherapy in combination with inotuzumab ozogamicin, an investigational product, in adults with CD22-positive non-Hodgkin's lymphoma. The trial will involve two arms. In one arm, subjects will receive chemotherapy regimen R-CVP (rituximab, cyclophosphamide, vincristine and prednisone). In the other arm, subjects will receive R-GDP (rituximab, gemcitabine, cisplatinum and dexamethasone). Subjects in both arms will also receive inotuzumab ozogamicin. Conditions: Lymphoma, B-Cell Intervention / Treatment: DRUG: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone, DRUG: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone Location: Canada, Japan, Korea, Republic of, United Kingdom, United States, Belgium, Singapore, Hong Kong, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Masking: NONE

Inclusion Criteria: * Dose escalation cohorts: subjects with diagnosis of CD22-positive Non-Hodgkin's Lymphoma (NHL) who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy. * Expanded maximum tolerated dose (MTD) confirmation and preliminary efficacy cohorts: subjects with diagnosis of CD22-positive NHL who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy or newly diagnosed subjects who are not candidates for anthracycline-based therapy. * At least 1 measurable disease lesion that is > 1 cm in the longest transverse diameter, with a product of the diameters > 2.25 cm2 by CT or magnetic resonance imaging (MRI). Exclusion Criteria: * Candidate for potentially curative therapy such as stem cell transplantation. * Prior allogeneic hematopoietic stem cell transplantation (HSCT). * Prior autologous transplantation, radioimmunotherapy, or other anti CD22 immunotherapy <= 6 months before the first dose of investigational product. * More than 3 previous combination chemotherapy (2 or more cytotoxics) anticancer regimens.

Study Objectives The primary objective of the study is to assess the activity of fulvestrant in postmenopausal women with advanced breast cancer failing treatment with non-steroidal or steroidal aromatase inhibitors by estimating the Clinical Benefit Rate Conditions: Breast Neoplasms Intervention / Treatment: DRUG: Fulvestrant Location: Belgium, Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological/cytological confirmation of breast cancer * progression under treatment with an aromatase inhibitor * At least one measurable or non-measurable lesion Exclusion Criteria: * Prior treatment for breast cancer with more than 2 different hormonal agents * More than 1 chemotherapy for advanced disease * Presence of life-threatening metastatic visceral disease

Study Objectives The purpose of the study is to evaluate the safety/tolerability, pharmacokinetics, and preliminary efficacy of GFH018 in combination with Toripalimab in patients with advanced solid tumors. Conditions: Advanced Solid Tumor Intervention / Treatment: DRUG: GFH018, DRUG: Toripalimab Location: Australia, China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Has histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors, progressed on at least first line therapy. * Has sufficient organ functions. * Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) ≤ 1. Subject with tumor involvement of the liver must have the Child-Pugh score of 0-7. * Life expectancy≥12 weeks. * Female or male subjects of child-bearing potential must agree to use effective contraceptive methods from the signing of the informed consent to 90 days after the last administration of the study drug. Fertile female subjects must have negative pregnancy test results within 7 days (inclusive) before administration. In addition, eligible patients in phase II part must meet the following criteria: * Histologically or cytologically confirmed diagnosis of unresectable or metastatic advanced tumors of specific types: hepatocellular carcinoma, cholangiocarcinoma/gallbladder cancer (except carcinoma of ampulla), pancreatic cancer, colorectal cancer, urothelium carcinoma, cervical cancer, head and neck squamous cell carcinoma, esophageal cancer and nasopharyngeal carcinoma. * At least one measurable lesion (according to RECIST 1.1). Exclusion Criteria: * Impaired cardiac function or clinically significant cardiac diseases. * With acute or chronic infections. * With active central nervous system metastases, including symptomatic brain metastases, meningeal metastases, spinal cord compression, or requiring treatment with glucocorticoids, antiepileptic drugs, anticonvulsant drugs, or mannitol. * With known active autoimmune diseases or a history of autoimmune diseases within 1 year prior to enrollment. * With clinically significant gastrointestinal diseases. * Uncontrollable or symptomatic ascites, pleural effusion or pericardial effusion. * With previous or present interstitial pneumonia. * With other uncontrolled systemic diseases, such as hypertension and diabetes. * Diagnosed with other malignant tumors within 3 years prior to starting study drug, except for cured carcinoma in situ of cervix and skin basal cell carcinoma. * With diseases requiring immunosuppressant therapy, or requiring prednisone > 10 mg/day or equivalent dose of similar drugs during the study period. * Subjects who have been treated with immunosuppressant drugs within 28 days prior to starting study drug, except for topical and inhaled cortisol and systemic cortisol of physiological dose (prednisone < 10 mg/day or equivalent dose of similar drugs). * Subjects who have received live vaccine, attenuated vaccine within 28 days prior to starting study drug, or plans to receive live vaccine, attenuated vaccine during treatment or within 30 days after the last administration. * Subjects who have been treated with radiotherapy, chemotherapy, targeted therapy, endocrine therapy, immunotherapy, and other anti-tumor therapies, or other investigational drugs within 5 half-life periods or within 28 days (whichever is shorter) prior to starting study drug. * Subject who has received major surgeries (except for needle biopsy) that may affect the administration or study evaluation within 28 days prior to starting study drug. * Subjects who have received strong inhibitor or inducer of CYP3A4, or herbal medicine/traditional Chinese medicines within 5 half-life periods or within 2 weeks (whichever is shorter) prior to starting study drug. * Subjects who have received combined treatment of drugs targeting TGF-β and PD-(L)1, including combination of antibody and small molecule or bispecific antibody. * Pregnant or lactating women.

Study Objectives The purpose of this study is to find a safe and effective dose of the combination of cetuximab (Erbitux) and Tarceva (erlotinib). Conditions: Neoplasms Intervention / Treatment: DRUG: Cetuximab + Erlotinib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Measurable disease * Life expectancy of at least 3 months * Must have at least one prior chemotherapy containing a platinum Exclusion Criteria: * Known or documented brain metastases * Prior cetuximab therapy

Study Objectives Clofarabine is a new chemotherapy drug which was FDA approved for the treatment of acute lymphocytic leukemia in children. This study is being done to see if Clofarabine works in adult patients with B-cell types of lymphoma. This research is being done to develop new treatments for patients with lymphoma whose cancer has returned or resisted treatment with previous chemotherapy. Conditions: B-Cell Lymphoma Intervention / Treatment: DRUG: Clofarabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult patients who are at least 18 years old * Histologically confirmed low grade or intermediate-grade B-cell lymphoma * Relapsed or refractory to at least one standard chemotherapy regimen. Patients who have received Rituximab alone without having received a cytotoxic agent are not eligible. * Measurable disease, defined by the Cheson lymphoma criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Life expectancy greater than 12 weeks * Laboratory values obtained ≤2 weeks prior to entry * Absolute neutrophil count (ANC) ≥ 1000 x 10 9/L * White blood cell (WBC) count > 2.5 x 10 9/L * Platelets ≥ 75 x 10 9/L * Hemoglobin (Hg) > 9.0 g/dL * Total bilirubin ≤2.0 mg/dL * Aspartate transaminase (AST)/alanine transaminase (ALT) ≤3 × upper limit of normal (ULN) * Serum creatinine ≤2.0 mg/dL * Normal cardiac function, defined as an ejection fraction ≥45% determined by pretreatment radionuclide ventriculography (RVG) or echocardiogram. * Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment. * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Exclusion Criteria: * Previously untreated B-cell lymphoma. * Received previous treatment with clofarabine. * Patients with known AIDS-related or HIV-positive lymphoma. * Autologous bone marrow or stem cell transplant within 6 months of study entry. * Prior radiotherapy to the only site of measurable disease. * Any medical condition that requires chronic use of oral high-dose corticosteroids greater than 20 mg/day prednisone. * Active autoimmune thrombocytopenia. * Use of investigational agents within 30 days or any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy. * Patients with an active, uncontrolled systemic infection considered to be opportunistic, life threatening, or clinically significant at the time of treatment or with a known or suspected fungal infection (ie, patients on parenteral antifungal therapy). * Active secondary malignancy. * Pregnant or lactating patients. * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * Patients with active or untreated central nervous system (CNS) lymphoma.

Study Objectives This is a prospective biomarker-stratified, randomised phase II study of preoperative CRT with temozolomide plus capecitabine in patients with locally advanced rectal cancer. The primary endpoint is pathologic complete response rates defined as total regression of the primary tumor. For each cohort of MGMT hypermethylated versus MGMT unmethylated, patients will be randomised (ratio 1:1 for each arm) into preoperative CRT with capecitabine or preoperative CRT with temozolomide plus capecitabine arms. According to the prior phase I results, MGMT hypermethylated arm is estimated as 70% of total patients and the target pathologic complete response rate was assumed as 35% in this population when treated with preoperative CRT with temozolomide and capecitabine (15% in the standard treatment arm or those with unmethylated MGMT). Investigator would like to demonstrate the superiority in terms of pathologic complete responses when treated with preoperative CRT with temozolomide plus capecitabine in patients with locally advanced rectal cancer, and to validate the predictive role of MGMT status Conditions: Advanced Rectal Cancer Intervention / Treatment: DRUG: Capecitabine plus temozolomide VS Capecitabine Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * To be eligible for inclusion, each patient must fulfill each of the following criteria: 1. Histologically confirmed adenocarcinoma of the rectum 2. Tumor located within 12cm of anal verge 3. Clinical stage of cT3-4Nany (cStage II) or cTanyN1-2 (cStage III) by rectal MRI 4. Available tumor samples for methylation-specific PCR (MSP) to investigate MGMT hypermethylation 5. Male or female aged over 20 years 6. Be ambulatory and have an Eastern Cooperative Oncology Group (ECOG) performance status0-1. 7. No prior systemic treatment (chemotherapy, immunotherapy) or radiation therapy 8. Adequate major organ functions as following: Hematopoietic function: ANC 1,500/mm3, Platelet 100,000/mm3 Hepatic function: serum bilirubin 2.0 mg/dL, AST/ALT levels 2.5 x UNL Renal function: serum creatinine UNL or Cockroft creatinine clearance 50 ml/min 9. Be willing and able to comply with the protocol for the duration of the study. 10. Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice. Exclusion Criteria: * Patients will be exluded from the study for any of the following reasons: * Histology other than adenocarcinoma or tumor arising from inflammatory bowel disease * Inadequate tumor sample for MGMT MSP * Any evidence of systemic metastasis * Unresected synchronous colon cancer; endoscopically resected synchronous colon cancer of pTis or pT1 is permitted * Subjects unable to swallow oral medication because of such as current or impending intestinal obstructions, but bypass surgery (colostomy or ileostomy) is permitted before study treatment * Uncontrolled or severe cardiovascular disease: * New York Heart Association class III or IV heart disease. * Unstable angina or myocardial infarction within the past 6 months. * History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality. * Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy. * Other malignancy within the past 5 years except cured non-melanomatous skin cancer, carcinoma in situ of the cervix, or thyroid papillary carcinoma. * Organ allografts requiring immunosuppressive therapy. * Psychiatric disorder or uncontrolled seizure that would preclude compliance. * Pregnant, nursing women or patients with reproductive potential without contraception. * Patients receiving a concomitant treatment with drugs interacting with 5-FU such as flucytosine, phenytoin, or warfarin et al. * Known dihydropyrimidine dehydrogenase (DPD) deficiency. * Known hypersensitivity to any of the components of the study medications.

Study Objectives The aim of the current study is to improve the outcome of patients with hematologic malignancies (in a phase I trial) and more specifically multiple myeloma (in a phase II trial) by 2 interventions: reduce the risk of graft-versus-host disease (GVHD) and improve the efficacy of the procedure decreasing the risk of relapses after transplant. Currently, the standard approach used in most centers to prevent graft-versus-host disease after allogeneic transplantation is based on the combination of a calcineurin inhibitor (cyclosporine or tacrolimus) plus a short course of methotrexate. Unfortunately, this strategy is far from ideal, since the risk of acute GVHD is in the range of 30-40% among patients receiving a matched related donor transplantation and even higher among patients receiving transplantation from an unrelated donor while the incidence of chronic GVHD is 60-70% among patients receiving peripheral blood progenitor cells from either a related or unrelated donor. As far as the patients with multiple myeloma (MM) is concerned, although the development of new drugs has markedly changed the outcome and management of these patients, allogeneic transplantation so far appears to be the only curative option, especially among those patients relapsing after first line treatment. Nevertheless, still new strategies within the allogeneic transplant setting are needed to improve its results. Relapses may occur either extramedullary (very common in this setting) or systemic. In order to reduce the risk of systemic relapses the investigators will use maintenance therapy with Lenalidomide (Len) which, together with bortezomib (Bz) should contribute to eradicate minimal residual disease (MRD). In case the patient do not obtain complete remission or near complete remission after transplant, in addition to the maintenance therapy, the investigators will use four intensification cycles with VRD (Bz-Len-Dexamethasone). In summary, the goal is to optimize the efficacy of allogeneic transplantation by two interventions: one focused on reducing the risk of relapse and the other on reducing the incidence of GVHD. Conditions: Hematologic Malignancies, Multiple Myeloma Intervention / Treatment: DRUG: Bz (Bortezomib), DRUG: Len (lenalidomide) Location: Italy, Spain, Sweden, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Phase I: For the first 10 patients: * Patients with any haematological malignancy in > CR1 (first complete remission) * Suitable related donor human leukocyte antigen (HLA)identical * Age > 18 and < 70 years For the 10 subsequent patients: * Patients with any haematological malignancy candidates to receive an allogeneic transplant * Suitable related or unrelated donor (a maximum of 1 mismatched is allowed) * Age > 18 and < 70 years phase II trial: * High-risk multiple myeloma patients at first relapse / second complete remission candidates to receive an allogeneic transplantation * Age:> 18 < 70 years. * Suitable donor, related or unrelated (a maximum of 1 mismatched is allowed) * Measurable disease * High risk first relapse is defined as: * First early relapse after Autologous Stem Cell Transplant (ASCT)< 24 months * First late relapses in case the patient does not achieve CR after second ASCT * First relapse in patients with poor cytogenetic features * All subjects must be able to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan. Exclusion Criteria: Any of the following: * Prior severe comorbidity such as: * Heart failure or previous infarction * Uncontrolled Hypertension * Arrhythmia * Cirrhosis * Peripheral neuropathy >Grade 2, 14 days prior to inclusion * Psychiatric disease * Prior history of other neoplasia except for carcinoma in situ in the last 10 years * Hypersensitivity to Bz, Boric acid mannitol. * Patients unable to use appropriate contraceptive methods * Patients who have received an investigational drug 30 days prior to inclusion * Positive human immunodeficiency virus (HIV) or active viral hepatitis * Patients with pericardial disease * Patients with acute diffuse infiltrative pulmonary disease * Patients not willing to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan * Patients not willing to receive thromboprophylaxis during the consolidation phase will not be eligible.

Study Objectives This will be a randomized, single-dose, open-label, two-period crossover study in 16 healthy subjects. The study will consist of two phases: Pre-randomization and Randomization. The Pre-randomization phase will have two periods: Screening and Baseline. In the Randomization Phase, subjects will be randomized to one of two possible treatment sequences (fed/fasted and fasted/fed). In each period, subjects will receive a single capsule containing 10 mg lenvatinib either with or without a standard breakfast. There will be a 2-week washout between treatments. Conditions: Cancer Intervention / Treatment: DRUG: HOPE, DRUG: HOPE Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Healthy, male or female subjects age greater than or equal to 18 years and less than or equal to 55 years old; * Body mass index (BMI) greater than 18 and less than or equal to 32 kg/m2 at Screening; * All females must have a negative serum B-human chorionic gonadotropin (B-hCG) test result or negative urine pregnancy test results at Screening and Baseline. Females of child-bearing potential must agree to use a medically acceptable method of contraception (eg, abstinence, an intrauterine device, a double-barrier method such as condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, an oral contraceptive or have a vasectomised partner) throughout the entire study period and for 30 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal women (defined as greater than age 50 and with at least 12 months of amenorrhea) or subjects who have been sterilized surgically or who are otherwise proven sterile (eg, bilateral tubal ligation with surgery at least 6 months prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 2 months prior to dosing). All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 12 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation; * Male subjects who are partners of women of childbearing potential must use, or their partners must use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, intrauterine device (IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug). Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously); * Provide written informed consent; * Are willing and able to comply with all aspects of the protocol. Exclusion Criteria: * Evidence of clinically significant cardiovascular, hepatic, gastrointestinal, renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities or a known history of any gastrointestinal surgery that could impact the pharmacokinetics of study drug; * A clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks, of dosing; * Evidence of organ dysfunction or any clinically significant deviation from normal in their medical history; * History of clinically significant drug or food allergies or presently experiencing seasonal allergies; * Evidence of clinically significant deviation from normal in physical examination, vital signs, electrocardiograms (ECG) or clinical laboratory determinations at Screening or Baseline; * Clinically significant ECG abnormality including a marked baseline prolongation of QT/QTc interval (eg repeated demonstration of a QTc interval greater than 500 msec), or a family history of prolonged QTc syndrome or sudden death; * History of drug or alcohol misuse within 6 months prior to Screening, or who have a positive urine drug test at Screening or Baseline; * Positive result for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV) screen, or a positive syphilis screen; * Diagnosed with acquired immune deficiency syndrome (AIDS), or test positive for human immunodeficiency virus (HIV); * Participated in another clinical trial less than 4 weeks prior to dosing or who are currently enrolled in another clinical trial; * Consumed caffeinated beverages or food within 72 hours prior to dosing; * Consumed grapefruit or grapefruit containing beverages or food within 72 hours prior to dosing; * Experienced a weight loss or gain of greater than 10% within 4 weeks of dosing; * Engaged in heavy exercise (greater than or equal to 1 hour/day 5 times/week) less than 2 weeks prior to Baseline (eg, marathon runners, weight lifters, etc.); * Received blood products within 4 weeks, or donated blood within 8 weeks, or donated plasma within 1 week, of dosing; * Hemoglobin level less than 12.0 g/dL; * Used prescription drugs within 2 weeks prior to screening; * Taken over-the-counter (OTC) medications within 2 weeks prior to dosing; * Any condition that would make him/her in the opinion of the Investigator or Sponsor, unsuitable for the study or who, in the opinion of the Investigator, is not likely to complete the study for any reason; * Inability to tolerate venepuncture and/or venous access; * History of depression, deliberate self harm or suicidal ideation.

Study Objectives Cancer cells may spread from the primary site to the vertebrae resulting in their deformity. The standard treatment for this case is removal of the cancer deposits in the vertebra and filling the induced cavity with a cement like substance. The investigators are studying the effects (good or bad) of adding samarium (a radioactive substance) to the cement that is injected into the induced cavity. Conditions: Cancer, Metastasis, Pain Intervention / Treatment: DRUG: Samarium (153SM) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * The patient must be 18 years of age or older * The patient must have histologically proven malignancy in the primary site (breast, prostate, or lung) * The patient must have a radiographic evidence of bone metastasis, and this must have been performed within 8 weeks prior to enrollment in the study. Acceptable studies include plain radiographs, radionuclide bone scans, computed tomography scans, magnetic resonance imaging, and PET-CT scans. * The patient must have an intact anterior wall of spinal canal * The patient must have significant pain (score 6 or above,)which appears to be related to the radiographically documented metastatic vertebra(e) in concern, as measured by the "Visual Analog Scale" * The patient must be surgically and medically accepted for vertebroplasty/kyphoplasty operation * Karnofsky Performance status >40 * Expected life expectancy of 6 months or greater, as estimated by the physician in charge. * The patient must sign a study specific informed consent prior to enrollment Exclusion Criteria: * Epidural soft tissue component * Patients with vertebral metastases and with clinical or radiographic evidence of spinal cord or cauda equina impingement (effacement) or compression * Inability to undergo anesthesia * Hematologic primary malignancies Patients received systemic radiotherapy (89SR or 153SM)within 30 days prior to enrollmen

Study Objectives Bortezomib (Velcade) has just recently been approved by the FDA for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. This study will determine if Velcade is effective in treating patients with multiple myeloma that have had no prior treatment for the disease. We will also use whole-genome scanning to identify drug response biomarkers in bone marrow samples as well as nerve fiber studies to compare nerves prior to the use of Velcade and after treatment with Velcade. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: bortezomib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of multiple myeloma based upon standard criteria * Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1 g/dl and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours. * Karnofsky performance status of > 60 * Hemoglobin > 8.0 g/dL * AST (SGOT) < 3 x ULN * ALT < 3 x ULN * Total bilirubin < 2 x ULN * Is infertile or is practicing an adequate form of contraception * 18 years of age or older Exclusion Criteria: * Prior treatment with systemic chemotherapy * Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes * Plasma cell leukemia * Calculated or measured creatinine clearance < 30 mL/minute within 14 days of enrollment * Grade 2 or greater peripheral neuropathy * Hypersensitivity to bortezomib, boron or mannitol * Severe hypercalcemia * HIV positive * Known active hepatitis B or C * New York Hospital Association Class III or IV heart failure * Second malignancy requiring concurrent treatment * Other serious medical or psychiatric illness * Pregnant women * Dialysis dependent patients

Study Objectives The objective of this study is to determine whether pomalidomide is safe and effective in reversing red blood cell (RBC)-transfusion-dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis (global study) and in reversing anemia in Chinese with MPN-associated myelofibrosis and severe anemia not receiving RBC-transfusions (China extension study only) Conditions: Primary Myelofibrosis, MPN-associated Myelofibrosis Intervention / Treatment: DRUG: Pomalidomide 0.5 mg, DRUG: Placebo, DRUG: Pomalidomide Location: Canada, Germany, Japan, Italy, Netherlands, Spain, United Kingdom, United States, Belgium, Australia, Austria, China, Russian Federation, Sweden, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Age ≥ 18 years * Myeloproliferative-neoplasm (MPN)-associated myelofibrosis * RBC-transfusion-dependence (global study): * Average RBC-transfusion frequency ≥ 2 units/28 days over at least the 84 days immediately prior to randomization. There must be no interval > 42 days without ≥ 1 RBC-transfusion. * Only RBC-transfusions given when the hemoglobin ≤ 90 g/L³ are scored in determining eligibility. * RBC-transfusions due to bleeding are not scored in determining eligibility. * RBC-transfusions due to chemotherapy-induced anemia are not scored in determining eligibility. * Severe anemia (China-specific extension): * ≥ 2 hemoglobin concentrations ≤ 80 g/L for ≥ 84 days immediately before the day of enrollment. * No RBC-transfusion within 6 months prior to enrollment. * Hemoglobin ≤ 130 g/L at randomization (global study); ≤ 80 g/L at enrollment in the China-specific extension. * Bone marrow biopsy within 6 months (global study only). * Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin and androgenic steroids * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Agree to follow pregnancy precautions as required by the protocol. * Agree to receive counseling related to teratogenic and other risks of pomalidomide. * Agree not to donate blood or semen. Exclusion Criteria: * Prior blood cell or bone marrow allotransplant. * Use of drugs to treat MPN-associated myelofibrosis ≤ 30 days before starting study drug. * Treatment with erythropoietin or androgenic steroids ≤ 84 days before starting study drug. * Anemia due to reasons other than MPN-associated myelofibrosis. * Pregnant or lactating females. * More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks * Prior history of malignancies,other than the disease being studied, unless the subject has been free of the malignancy for ≥ 5 years with the following exceptions: * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T 1a or T 1b using TNM \[tumor, nodes, metastasis\] clinical staging system) * Human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. * Prior treatment with pomalidomide. * Allergic reaction or rash after treatment with thalidomide or lenalidomide * Any of the following laboratory abnormalities: * Neutrophils < 0.5x10\^9 /L * Platelets < 25 x 10\^9 /L * Estimated glomerular filtration rate (kidney function) < 30 mL/min/1.73 m² * Aspartate aminotransferase (AST) and alanine transaminase (ALT) > 3.0 x upper limit of normal (ULN) * Total bilirubin ≥ 4 x ULN; * Uncontrolled hyperthyroidism or hypothyroidism. * Deep venous thrombosis (DVT) or pulmonary embolus (PE) < 6 months before starting study drug * Clinically-important heart disease within the past 6 months

Study Objectives This study is being carried out to see if ZD4054 (Zibotentan) is effective in treating prostate cancer and spread of cancer to the bone, and if so, how it compares with placebo (sugar pill). The study will also provide further information on the safety of ZD4054 (Zibotentan). Conditions: Prostate Cancer Intervention / Treatment: DRUG: ZD4054 15 mg, DRUG: Placebo, DRUG: ZD4054 10 mg Location: Indonesia, Finland, Norway, Canada, Netherlands, Switzerland, United Kingdom, Denmark, United States, Belgium, Australia, Sweden, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Surgically or medically castrated * Bone metastasis * Rising PSA Exclusion Criteria: * Opiate use * Prior chemotherapy

Study Objectives This multicenter, open-label, uncontrolled phase II trial evaluates safety and efficacy of post-operative chemoradiation in combination with cetuximab in squamous cell carcinoma of the head and neck. Conditions: Head and Neck Cancer Intervention / Treatment: DRUG: Cetuximab Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed written informed consent; * Males or females between 18 and 70 years of age; * Surgically resected squamous cell carcinomas of the hypopharynx, oropharynx, larynx and oral cavity with high risk of locoregional recurrence not more than 6-9 weeks (maximum) ago; * To be categorized as high risk patients have to fulfil at least one of the following criteria: * R0 - resection <5 mm margin * R1 - resection * Extracapsular nodal extension; * no previous chemotherapy, radiotherapy; * Performance status ECOG: 0 - 1; * Contraception in male and female patients if of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing; * Adequate renal, liver and hematological functions (within maximum 9 weeks until surgery): * Adequate bone marrow function: neutrophils > 1.5 x 10\^9/L, platelets > 100 x 10\^9/L, hemoglobin > 10.0 g/dL * Adequate liver function: Bilirubin < 2.0 mg/dL, AST, ALT, AP, γ-GT < 3 x ULN * Adequate renal function: creatinine clearance > =60 ml/min * No distant metastases; Exclusion Criteria: * Nasopharyngeal carcinoma; * R2 resection; * Invalid informed consent; * Performance Status > 1; * Previous chemotherapy or radiotherapy for carcinoma of the head and neck; * Prior exposure to EGFR pathway targeting therapy; * Other serious illness or medical conditions: * Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4; * Clinically significantly abnormal electrocardiogram (ECG) or left ventricular ejection fraction (LVEF) below the institutional range of the normal * Significant neurologic or psychiatric disorders including dementia or seizures; * Active uncontrolled infection; * Active disseminated intravascular coagulation; * Other serious underlying medical conditions which could impair the ability of the patient to participate in the study; * Symptomatic peripheral neuropathy National Cancer Institute-Common Toxicity Criteria (NCI-CTC v3.0) grade 2 or ototoxicity grade 2, except if due to trauma or mechanical impairment due to tumor mass; * Having participated in another therapeutic clinical trial or any investigational agent in the preceding 30 days; * Known allergic/hypersensitivity reaction to any of the components of the treatment; * Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding; * Known drug abuse; * Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix; * Legal incapacity or limited legal capacity; * Sensitivity and incompatibility against 5-Fluorouracil * Sensitivity and incompatibility against platinum-compounds * Known incompatibilities >grade 3 towards cetuximab * expected incompliance of patient (e.g. in case of severe alcohol addiction) * Dental evaluation: Pre treatment dental care before start of radiochemotherapy (approximately 8 to 10 days lapse-time is needed for complete recovery before initiation of radiation therapy).

Study Objectives The purpose of this research is to apply this smoking cessation program on oral cancer patients, and to analyze the effectiveness of it. Conditions: Oral Cancer Intervention / Treatment: BEHAVIORAL: smoking cessation program, BEHAVIORAL: Lifestyle counseling Location: Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * clinical diagnosis of oral cancer * current smoker

Study Objectives The purpose of this trial is to evaluate the efficacy and safety of NPC-12G gel (topical formulation of sirolimus) versus placebo gel to facial angiofibroma and other skin lesions in patients with tuberous sclerosis complex (TSC) Conditions: Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule, Plaque Intervention / Treatment: DRUG: NPC-12G gel, DRUG: Placebo gel Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Male or female patients 3 years old or greater at the time of informed consent * Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012) * Patients with three or more papules of angiofibroma ( >= 2 mm in diameter with redness in each) on the face at screening tests * Patients who are not suitable for therapy with laser or surgery, or who do not want therapy with laser or surgery * Patients or his/her guardian who give a written informed consent in understanding and willingness after having received enough explanation of the test drug and the current trial plan Exclusion Criteria: * Patients who are hard to apply the test drug topically with keeping compliance * Patients with clinical findings such as erosion, ulcer and eruption on or around the lesion of angiofibroma, which may affect assessment of safety or efficacy * Patients who are hard to be taken pictures of their lesions adequately in such cases that they may not follow instruction of stillness * Patients with a history of hypersensitivity to alcohol or allergy to sirolimus * Patients who have complications such as malignant tumor, infection, serious heart disease, hepatic function disorder, renal function disorder or blood disorders which severity are considered by investigator as grade 2 or more severe with reference to ''Concerning classification criteria for seriousness of adverse drug reactions of medical agents'' * Patients who have complications such as diseases unsuitable for the trial participation, for examples, uncontrolled diabetes (fasting blood glucose level >140 mg/dL or postprandial blood glucose level > 200 mg/dL), dyslipidemia (cholesterol level > 300 mg/dL or > 7.75 mmol/L, triglycerides level > 300 mg/dL or > 3.42 mmol/L), etc. * Patients who have taken drugs with mTOR inhibitory action including sirolimus, everolimus or temsirolimus within 12 months before the initial registration * Patients who have applied topical tacrolimus on the lesion of angiofibroma within 3 months before the initial registration * Patients who have received therapy with laser or surgery to the lesion of angiofibroma within 6 months before the initial registration * Female patients who may be pregnancy or are lactating * Patients who cannot agree to take appropriate measures of contraception until completion of post-treatment phase or follow-up period after discontinuation from informed consent * Patients who have participated in other clinical trial and have taken a trial drug within 6 months before the initial registration * Others, patients who are considered by the investigator as unsuitable for participation in the trial

Study Objectives The purpose of this study is to assess the safety and tolerability and the pharmacokinetics (PK) of INCMGA00012 (PD-1 Inhibitor), INCB001158 (Arginase Inhibitor), and the combination in Japanese participants with advanced solid tumor malignancies. Conditions: Advanced Solid Tumors, Metastatic Solid Tumors Intervention / Treatment: DRUG: Retifanlimab, DRUG: INCB001158, DRUG: Retifanlimab + INCB001158 Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participant is Japanese * Histologically or cytologically confirmed diagnosis of any locally advanced or metastatic solid tumors not amenable to local or other curative therapy. * Participants with nonevaluable lesions are allowed. * Life expectancy > 3 months. * Eastern Cooperative Oncology Group performance status 0 to 1. * Female participants agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration. * Female participants of childbearing potential must understand and accept that pregnancy must be avoided during participation in the study. * Male participants should avoid unprotected sex with women of childbearing potential and refrain from donating sperm during participation the study. Exclusion Criteria: * Receipt of anticancer therapy or participation in another interventional clinical study within 14 days before the first administration of study drug with the following exceptions: Immunotherapy or biological therapy (eg, monoclonal antibodies) within 21 days the first administration of study drug; 6 weeks for mitomycin-C or nitrosoureas; 7 days for tyrosine kinase inhibitors. * Radiotherapy within 14 days of first dose of study treatment with the following exceptions: 28 days for pelvic radiotherapy; 6 months for thoracic region radiotherapy that is > 30 Gy. * Toxicity of prior therapy and/or complications from surgical intervention that has not recovered to ≤ Grade 1 or baseline within 7 days before starting study drug treatment (with the exception of anemia not requiring transfusion support and any grade of alopecia). Note: Endocrinopathy, if well-managed, is not exclusionary and should be discussed with sponsor medical monitor. * Receipt of prior systemic treatment with an arginase inhibitor * Immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy is recommended (per product label or consensus guidelines), OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well controlled on replacement hormones). * Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent). * Known active central nervous system metastases and/or carcinomatous meningitis. * Known active hepatitis A virus, hepatitis B virus, or hepatitis C virus infection. * Known HIV infection. * Active infections requiring systemic therapy. * Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures and/or known hypersensitivity ≥ Grade 3, or severe reaction, to study treatments or any of their excipients or additives. * Participants with impaired cardiac function or clinically significant cardiac disease. * Evidence of interstitial lung disease or active, noninfectious pneumonitis or a history of interstitial lung disease. * Participant is pregnant or breastfeeding.

Study Objectives Uterine fibroid embolization (UFE) is now an accepted treatment of uterine fibroids. However the procedure is often very painful and, in many centres, patients are admitted overnight with patient controlled analgesic (PCA) pumps for pain control and discharged the next day with heavy pain medications. The goal of this study is to evaluate the effectiveness of a superior hypogastric nerve block (SHGNB) in controlling the pain post-UFE. Conditions: Leiomyoma Intervention / Treatment: PROCEDURE: Superior hypogastric nerve block, DRUG: 0.75% Ropivacaine, PROCEDURE: Subcutaneous injection, DRUG: 1% Xylocaine Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * All women with symptomatic fibroids or adenomyosis that have requested and been approved for uterine artery embolization * Ability to comply with the requirements of the study procedures Exclusion Criteria: * Patients in whom the vascular anatomy prevents access to the superior hypogastric nerve plexus safely * Patients who have known allergy to the anesthetic agent * Patients with signs of skin infection at the entry site of the needle used to place the nerve block * Patients with signs of infection such as fever * Patients with history of inflammatory bowel disease of with signs of colitis * Patients with uncorrectable abnormal coagulation status (INR >1.5 and plt < 50000 without use of anticoagulation agents) * Patients with preexisting conditions, which, in the opinion of the investigator, interfere with the conduct of the study. * Patients who are uncooperative, cannot follow instructions, or who are unlikely to comply with follow-up appointments or fill-out the post-procedural pain questionnaires. * Patients with a mental state that may preclude completion of the study procedure or is unable to provide informed consent

Study Objectives The purpose of this study is to evaluate the effectiveness of Bortezomib when added to standard chemotherapy medicine(s) for treatment of Multiple Myeloma. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Bortezomib, DRUG: Melphalan, PROCEDURE: Autologous Stem Cell Transplant, DRUG: Fludarabine, PROCEDURE: Allogeneic Stem Cell Transplant Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Multiple Myeloma Criteria(International Uniform Response Criteria for Multiple Myeloma) * Patients with responsive disease after any line of induction therapy * A complete response * A very good partial response * A partial response * Patients greater than or equal to 18 years of age are eligible. There is upper age limit of 60 years for allogeneic transplants. * Patients must have a histologically confirmed diagnosis. * All patients should have a life expectancy of at least 12 weeks. * Patients must have undergone a complete psychosocial evaluation and have been considered capable of compliance. * Meet the following criteria for allogeneic hematopoietic cell transplant: * Must have an identified donor match defined as: HLA-A, HLA-B, HLA- C, DRB1 8/8 allele matched sibling, family member, or unrelated donor. \[7/8 would go on separate mismatched trials\] and be < 60 years of age. * Calculated hematopoietic cell transplantation-specific comorbidity index (HCT-CI) <3 Exclusion Criteria: * Patients who do not achieve at least a partial response (PR) by the criteria mentioned above with induction therapy. * Patient has a platelet count of <30 x 10\^9/L within 14 days before enrollment. * Patient has >= Grade 2 peripheral neuropathy within 30 days before enrollment. * Patient has an absolute neutrophil count of <1.0 x 10\^9/L within 30 days before enrollment. * Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant in order for the subject to be considered eligible. Left ventricular ejection fraction (LVEF) by multiple gated acquisition (MUGA) scan < 40%. * Patient has hypersensitivity to bortezomib, boron or mannitol. * Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. * Patient has received other investigational drugs with 30 days before enrollment * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Patients with a diffusing capacity of lung for carbon monoxide (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are ineligible. * Patients with a total bilirubin greater than 2.0 mg/dL excluding Gilbert's syndrome and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible. * Calculated creatinine clearance <= 30 ml/min within 30 days before enrollment * Patients with active infections are ineligible. * Patients who are HIV positive are ineligible. * Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture, and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible. * Patients with uncontrolled insulin-dependent diabetes mellitus defined as a random glucose level of > 400 in the 30 days prior to initiation of study therapy; or uncompensated major thyroid or adrenal dysfunction are ineligible. * Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of >= 2(Karnofsky < 50%) are ineligible. * Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to bone pain, may be enrolled. * Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to a potentially reversible disease-related problem, may be enrolled. * Patients with any previous malignancy other than non-melanoma skin cancer are ineligible, unless the patient is without evidence of disease >= 5 years after the treatment for the cancer was completed.

Study Objectives Chemotherapy given together is a standard way to treat your cancer. One standard treatment includes a combination of docetaxel, cisplatin, and fluorouracil. However, the original combination of these three drugs can cause many side effects. This study is being done to find out if these three drugs can be given at lower doses more often, with fewer side effects and still maintain the same benefit as the standard way of giving this three drug combination. If your tumor overexpresses a protein called Her2, you are also eligible to receive trastuzumab with chemotherapy. Trastuzumab is a medicine that has been approved by the US Food and Drug Administration for the treatment of Her2 positive breast cancer. Trastuzumab is now also a standard treatment in combination with chemotherapy for the treatment of Her2 positive stomach cancer. If your tumor is Her2 positive, you would receive the modified administration schedule of docetaxel, cisplatin, and fluorouracil with trastuzumab. Conditions: Gastroesophageal Junction Adenocarcinoma, Gastric Cancer Intervention / Treatment: DRUG: Docetaxel, Leucovorin, Fluorouracil, Cisplatin, DRUG: Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen, DRUG: Docetaxel, Leukvorin, Flurouracil, Cisplatin, Trastuzumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients must have histologically or cytologically confirmed metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. GEJ adenocarcinoma may be classified according to Siewert's classification type I, II, or III\[43\]. * Histological documentation of local recurrence or metastasis is strongly encouraged, unless the risk of such a procedure outweighs the potential benefit of confirming the metastatic disease. * If no histologic confirmation, then the metastases or recurrence will require documentation by a 2nd radiographic procedure (eg. PET/CT scan or MRI in addition to the CT scan). If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation will be required. * Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease. Measurable disease is defined as that which can be measured in at least one dimension as > 20 mm with conventional techniques, or >10 mm by high resolution imaging. Disease that is identified on radiology studies, but does not meet the criteria for measurable disease, is considered non-measurable. * Patients may have received no prior chemotherapy for metastatic or unresectable disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration. Patients may not have received prior docetaxel or cisplatin. * Age 18 years or older. * Karnofsky performance status > than or = to 70% (ECOG performance status 0-1). * Peripheral neuropathy < than or = to grade 1. * Hematologic (minimal values): * White blood cell count > than or = to 3000/mm3 * Absolute neutrophil count > than or = to 1500 cells/ mm3 * Hemoglobin > than or = to 9.0 g/dl * Platelet count > than or = to 100,000 / mm3 * Hepatic (minimal values): * Total bilirubin < or = to 1.5 \* \* AST and ALT and Alkaline phosphatase must be within the eligible range. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used. Patients with alkaline phosphatase elevation secondary to the bony metastases rather than liver dysfunction may proceed with treatment on protocol after discussion with the principal investigator. * Kidney function (minimal values): \* Serum creatinine < than or = to 1.5 mg/dl - if serum creatinine is 1.2-1.5 mg/dl, the creatinine clearance (either measured or calculated) must be 50 ml/min or greater * The patient has a PT (INR) < than or = to 1.5 and an PTT < than or = to 3 seconds above the upper limits of normal if the patient is not on anticoagulation. If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment: * The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin * The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices) * Women of childbearing potential have a negative pregnancy test. * Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy. * Patients must have HER2-positive (FISH+ or IHC 3+) metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma to be eligible for trastuzumab. For the purposes of this protocol, FISH+ is defined as HER2:CEP17 ratio ≥ 2.0. Biopsy samples with cohesive IHC3+ or FISH+ clones are considered HER2 positive irrespective of size, i.e.<10%. FISH+ defined as >2 HER2:CEP17. * Patients who are receiving trastuzumab must have a left ventricular ejection fraction of ≥ 50%. Exclusion Criteria: * Patients who have received previous chemotherapy for the treatment of metastatic or unresectable gastric or GEJ adenocarcinoma are ineligible. * Patients who have received previous pre- or post-operative chemotherapy or chemoradiation are ineligible if therapy was completed less than 6 months prior to study registration. Patients must have recovered from adverse events from any previous therapy. * Patients who have received previous docetaxel or cisplatin. * Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer. * Patients with brain or central nervous system metastases, including leptomeningeal disease. * Pregnant (positive pregnancy test) or breast feeding. * Serious, non-healing wound, ulcer, or bone fracture. * Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months * Evidence of bleeding diathesis or coagulopathy. * History of a stroke or CVA within 6 months * Clinically significant peripheral vascular disease. * Clinically significant hearing loss or ringing in the ears. * Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80. * Inability to comply with study and/or follow-up procedures. * Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial. * For patients who are Her2 positive and will be treated on the trastuzumab + mDCF cohort, prior trastuzumab treatment is not allowed. * For patients who are Her2 positive and will be treated on the trastuzumab+mDCF cohort, left ventricular function <50%

Study Objectives The purpose of this study is to assess the ability of darbepoetin alfa to maintain hemoglobin concentrations greater than or equal to 10 g/dL when administered every 3 weeks (Q3W). Conditions: Neoplasms, Anemia Intervention / Treatment: DRUG: darbepoetin alfa Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: - Subjects with non-myeloid malignancies - Anemia (screening hemoglobin concentration greater than or equal to 10.5 g/dL but less than or equal to 12.0 g/dL) related to cancer and chemotherapy - At least 8 additional weeks of cyclic chemotherapy planned regardless of schedule - Karnofsky Performance Status of greater than or equal to 50% - Serum creatinine concentration less than or equal to 2.0 mg/dL Exclusion Criteria: - Iron deficiency - Red blood cell (RBC) transfusion within 4 weeks of screening - Unstable cardiac disease

Study Objectives This randomized phase II trial studies how well giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before donor hematopoietic cell transplant works in treating younger patients with juvenile myelomonocytic leukemia. Giving chemotherapy before a donor hematopoietic transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before a donor stem cell transplant is more effective in treating juvenile myelomonocytic leukemia. Conditions: Juvenile Myelomonocytic Leukemia Intervention / Treatment: PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Busulfan, DRUG: Cyclophosphamide, DRUG: Fludarabine Phosphate, OTHER: Laboratory Biomarker Analysis, DRUG: Melphalan, DRUG: Mycophenolate Mofetil, OTHER: Pharmacological Study, DRUG: Tacrolimus Location: New Zealand, United States, Australia, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients must have a strong clinical suspicion of JMML, based on a modified category 1 of the revised diagnostic criteria; specifically, eligible patients must have all of the following: * Splenomegaly * Absolute monocyte count (AMC) > 1000/uL * Blasts in peripheral blood (PB)/bone marrow (BM) < 20% * For the 7-10% of patients without splenomegaly, the diagnostic entry criteria must include all other features described above and at least 2 of the following criteria: * Circulating myeloid precursors * White blood cell (WBC) > 10,000/uL * Increased fetal hemoglobin (HgbF) for age * Sargramostim (GM-CSF) hypersensitivity OR, patients must have been previously diagnosed with JMML * Patients must be previously untreated with HCT * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: * Patients with a known germline mutation of PTPN11 (Noonan?s Syndrome) are not eligible * Patients with a known history of NF1 (Neurofibromatosis Type 1) and either * A history of a tumor of the central nervous system (astrocytoma or optic glioma), or * A malignant peripheral nerve sheath tumor with a complete remission of < 1 year are not eligible * Human immunodeficiency virus (HIV) positive patients are not eligible

Study Objectives The purpose of this study was to evaluate the safety and tolerability of multiple ascending doses of single-agent M4344 administered twice-weekly (BIW), twice daily (BID) or once daily dose schedule in participants with advanced solid tumors. This investigation is a three part study examining M4344 alone and in combination with carboplatin to determine the safety and maximum tolerated dose. Conditions: Solid Tumor, Advanced Solid Tumor Intervention / Treatment: DRUG: M4344 10 mg BIW, DRUG: M4344 20 mg BIW, DRUG: M4344 40 mg BIW, DRUG: M4344 80 mg BIW, DRUG: M4344 160 mg BIW, DRUG: M4344 300 mg BIW, DRUG: M4344 450 mg BIW, DRUG: M4344 700 mg BIW, DRUG: M4344 1050 mg BIW, DRUG: M4344 1200 mg BIW, DRUG: M4344 100 mg BID, DRUG: M4344 150 mg QD, DRUG: M4344 250 mg QD, DRUG: M4344 350 mg QD, DRUG: M4344 400 mg, DRUG: M4344 500 mg, DRUG: Carboplatin Location: United States, Netherlands, United Kingdom, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Part A, A2 and A3: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit * Part B1: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit and/or participants must have progressed after at least 1 prior chemotherapy regimen in the metastatic setting, and for which carboplatin would be considered standard of care. * Part C: Participants with 1 histologically or cytologically confirmed malignant advanced solid tumors for which no recommended standard therapy is available (that is, participants who have exhausted all standard of care options according to National Comprehensive Cancer Network \[NCCN\] Guidance) which may convey clinical benefit, and whose tumor has at least 1 of the following biomarkers as determined by a central trial assay or by an assay with appropriate regulatory status: - C1 or C4: loss-of-function mutations in the gene ARID1A - C2 or C5: loss-of-function mutations in the genes ATRX and/or DAXX - C3 or C6: loss-of-function mutation in the gene ataxia telangiectasia mutated (ATM) - This mandatory biomarker assessment must be conducted during screening on a fresh tumor biopsy (or a biopsy obtained after the end of the previous treatment regimen). If this is not possible for medical reason(s), available archival tumor material can be used (historical data should not be used to confirm biomarker status) * Measurable disease either according to RECIST criteria (Version 1.1) * WHO performance status of 0 or 1 * Life expectancy of greater than or equal to (>=)12 weeks * Hematological and biochemical indices within acceptable ranges at Screening * Other protocol defined inclusion criteria could apply Exclusion Criteria: * Radiotherapy, unless brief course for palliative therapy, endocrine therapy, target-specific therapy, immunotherapy, or chemotherapy during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C, and 4 weeks for investigational medicinal products) or 4 drug half-lives before first dose of study drug, whichever is greater * Part B1: More than 6 cycles of prior therapy with carboplatin * Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the investigator should not exclude the participant * Part B1: Any known history of Grade 4 thrombocytopenia with any prior chemotherapy regimen * Brain metastases unless asymptomatic, treated, stable, and not requiring steroids for at least 4 weeks before first dose of study drug * Female participants who are already pregnant or lactating, or plan to become pregnant within 6 months of the last dose of study drug are excluded. Female participants of childbearing potential must adhere to contraception guidelines. Female participants will be considered to be of nonchildbearing potential if they have undergone surgical hysterectomy or bilateral oophorectomy or have been amenorrheic for over 2 years with a screening serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females. * Male participants with partners of childbearing potential must agree to adhere to contraception guidelines. Men with pregnant or lactating partners or partners who plan to become pregnant during the study or within 6 months of the last dose of study drug are excluded. * Major surgery less than or equal to (<=) 4 weeks before first dose of study drug or incomplete recovery from a prior major surgical procedure * Serious co-morbid medical conditions, including clinically-significant cardiac disease * Other protocol defined exclusion criteria could apply

Study Objectives To evaluate efficacy, safety, and pharmacokinetics of BAY 43-9006 in patients with unresectable and/or metastatic renal cell cancer (RCC) who have failed at least one cytokine containing regimen. Conditions: Carcinoma, Renal Cell Intervention / Treatment: DRUG: Nexavar (Sorafenib, BAY43-9006) Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients who suffer from unresectable and/or metastatic, measurable RCC histologically or cytologically documented. * Patients with rare subtypes of RCC, such as pure papillary cell tumor, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors, are excluded from study participation. Exclusion Criteria: * More than three regimens of previous treatment for RCC

Study Objectives Patients will receive methotrexate at a dose of 45 mg/m2 administered weekly for 4 consecutive weeks as an iv infusion along with a nutritional supplement administered two hours before the methotrexate. One hour before the methotrexate treatment the patients will be administered the first infusion of the day of either TK112690 or placebo depending on randomization. Five hours after the methotrexate treatment the patients will be administered the second treatment of either TK112690 or placebo depending on randomization. The TK112690 dose will be 45 mg/kg. Conditions: Mucositis Intervention / Treatment: DRUG: TK-112690, DRUG: Placebo TK-112690 Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria * Male and female subjects over 18 years old with a histologically or cytological confirmed diagnosis of locally residual, recurrent or metastatic SCCHN. * Subject must have failed at least one courses of non-MTX chemotherapy, or one course of non-MTX chemotherapy and chemo radiation for treating their SCCHN. * No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening. * No other concurrent, active, invasive malignancies. * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Must have a life expectancy of at least 6 months. * History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy. * No active angina or uncontrolled arrhythmia. * No detectable infection including hepatitis B/C and HIV. * Not pregnant or nursing. Women of childbearing potential must have a negative urine pregnancy test at screening and on the day before dosing and must use medically acceptable methods of birth control. Acceptable methods of birth control include oral or transdermal contraceptives, condoms, spermicidal foam, IUD, progestin implant or injection, abstinence, vaginal ring, or sterilization of partner. The reason for non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or post-menopausal for ≥ 1 year, must be specified in the patient's medical history file and CRF. * Must have adequate organ and immune function as indicated by the following laboratory values: Parameter Laboratory Values Serum creatinine ≤1.5 x ULN Est. creatinine clearance ≥45 mL/min Total bilirubin ≤2.0 mg/dL (≤34.2 μmol/L) AST \& ALT ≤3 x ULN Absolute granulocytes ≥1.5 x 109 cells/L Platelets ≥100,000/µL ● Be able to read and understand, and provide a signature or thumb impression on the Informed Consent Form (ICF) before entering the study. Exclusion Criteria: * Subject has not failed at least one courses of non-MTX chemotherapy or one course of non-MTX chemotherapy and chemo radiation for treating their SCCHN. * Uncontrolled active infection. * Current mucositis (>Grade 1). * Pregnant or nursing mother. * Prior history of a cerebrovascular accident or hemorrhage. * Congestive heart failure, as defined by New York Heart Association class III or IV. * Uncontrolled hypertension. * Active psychiatric/mental illness making informed consent or useful clinical follow-up unlikely. * Subjects who have previously been enrolled into this study and subsequently withdrew. * Subject receiving other investigational agent(s). * Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids). * Any significant systemic illness, unstable or severe medical condition(s) that could put the subject at risk during the study, interfere with outcome measures, or affect compliance with the protocol procedures such as intercurrent infection and/or autoimmune disease, ie, any condition that compromises the immune system. * Known or suspected intolerance or hypersensitivity to the study materials (TK-112690 and/or excipients or closely related compounds). * Subjects, who have received, or plan to receive, radiation or chemotherapy within 4 weeks of screening. * Subjects that have a history of poor compliance in clinical research studies. * Subjects that have participated in any other investigative clinical trial in the past 4 weeks.

Study Objectives This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations. Conditions: HER2-mutant Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: neratinib, DRUG: temsirolimus Location: United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria * Aged ≥18 years at the time of signing the informed consent. * Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage IV). * Documented somatic ErbB2 (HER2) activating mutation. * Patients with anaplastic lymphoma kinase (ALK) translocations must have received crizotinib, except for cases of intolerable toxicity to crizotinib. * At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). * Eastern Cooperative Oncology Group (ECOG) status <2. * Left ventricular ejection fraction (LVEF) ≥50% measured by multiple -gated acquisition scan (MUGA) or echocardiogram (ECHO). * Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause. * Men and women of childbearing potential must agree and commit to the use of a highly effective method of contraception, as determined to be acceptable by the Investigator, from the time of informed consent until 3 months after the last dose of the investigational products. * Provide written, informed consent to participate in the study and follow the study procedures. Exclusion Criteria * Previous treatment with any investigational agent ≤14 days prior to the initiation of investigational products. * Previous treatment with any strong inhibitor and/or inducer of CYP3A4 enzyme or sensitive P-glycoprotein (P-gp) substrates ≤30 days prior to the initiation of investigational products. * Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia. * Major surgery <30 days of starting treatment. * Chronic steroid use (prednisone >12.5 mg/day or dexamethasone >2 mg/day, excluding inhaled steroids). * Currently breast feeding. * Symptomatic or unstable brain metastases. * QTc interval >0.450 seconds for men and >0.470 seconds for women, or known history of QTc prolongation or Torsades de Pointes (TdP). * Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 4.0 \[CTCAE v.4.0\] diarrhea of any etiology at baseline). * Prior exposure to neratinib or mTOR inhibitor. * Active infection or unexplained fever >38.5°C (101.3°F). * Unable or unwilling to swallow tablets. * Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study. * Known hypersensitivity to any component of the investigational products. * Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin \[HbA1c\] >6.5%). * Screening laboratory assessments outside the following limits: ANC <1000/μL (<1.0 x 109/L), Platelet count <75,000/μL (<75 x 109/L), Hemoglobin <8 g/dL, transfusions allowed, must be at least 7 days prior to baseline, Total bilirubin >1.5 x institutional upper limit of normal (ULN), AST and/or ALT 5 minutes, Creatinine clearance <50 mL/min.

Study Objectives This study is being done in 2 parts. The first part is to determine the dose of RAD001 that should be used in combination with sorafenib. The second part is using the above determined dose of RAD001 in combination with sorafenib to see how effective these 2 drugs are against advanced kidney cancer. Participants will be asked to keep a pill diary. Conditions: Kidney Cancer Intervention / Treatment: DRUG: Sorafenib, DRUG: RAD001 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Clinically documented metastatic or unresectable locally recurrent clear cell renal carcinoma * Previous removal of kidney except if the size of the tumor was less than 5 cm or there was extensive liver or bone metastasis * May have had no prior chemotherapy or up to 1 prior treatment regimen with immunotherapy or chemotherapy * Performance status of 0-1 * Measurable disease * Adequate liver, renal, and bone marrow function * Must be able to give written informed consent * Women able to become pregnant must have a negative pregnancy test * Must be 18 or over * Must be able to swallow pills Exclusion Criteria: * Prior treatment with sorafenib or m-TOR inhibitors * History of acute MI within the last 6 months * Active brain metastasis or patients with meningeal metastases * Prior treatment for another cancer in the last 5 years * Prior bleeding problems; coughing up or vomiting blood * Non-healing wounds, ulcer, or long bone fracture * Chronic use of systemic steroids or immunosuppressive agents * Uncontrolled hypertension Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

Study Objectives To determine the safety, tolerability and effects of CPG 7909 (the study drug) when given with chemotherapy to patients with melanoma. Conditions: Carcinoma, Melanoma Intervention / Treatment: DRUG: CPG 7909 Injection, DRUG: dacarbazine, DRUG: Chemotherapy, DRUG: CPG 7909 Injection, DRUG: CPG 7909 Injection Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed melanoma that is metastatic. * Measurable disease according to the RECIST criteria. * Karnofsky Performance Status of > 70. Exclusion Criteria: * Prior treatment with anti-neoplastic biologic or chemotherapy for recurrent or metastatic disease (except one course of adjuvant immunotherapy and/or adjuvant chemotherapy other than DTIC). * Suspected or known CNS metastases.

Study Objectives This is an open-label, multicenter, Phase I study to evaluate the safety, tolerability, and PK of escalating doses of DLYE5953A administered to patients with incurable, locally advanced, or metastatic solid malignancy that has progressed on standard therapy. The Phase I study consists of two stages: Stage 1 dose-escalation and Stage 2 expansion in selected patients. In Stage 1, a 3 + 3 dose-escalation design will be used to examine the safety, tolerability, and PK of increasing doses of DLYE5953A. In Stage 2, patients will be enrolled to further characterize the safety, tolerability, and PK of the proposed dose and schedule for future studies. Conditions: Neoplasms Intervention / Treatment: DRUG: DLYE5953A, DRUG: DLYE5953A Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age >= 18 years * ECOG performance status of 0 or 1 * Histologically or cytologically documented advanced or metastatic solid tumors for which established therapy either does not exist or has proven ineffective or intolerable * Measurable disease by RECIST v1.1 with at least one measurable target lesion Exclusion Criteria: * Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of DLYE5953A * Oral kinase inhibitors approved by local regulatory authorities may be used within 2 weeks prior to initiation of DLYE5953A, provided that any clinically relevant drug-related toxicity has completely resolved and prior approval is obtained from the Medical Monitor

Study Objectives This phase I/II trial is studying the side effects and best dose of everolimus when given together with sorafenib tosylate and to see how well they work in treating patients with advanced solid tumors and metastatic pancreatic cancer that does not respond to gemcitabine hydrochloride. Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Giving sorafenib tosylate together with everolimus may kill more tumor cells. Conditions: Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific Intervention / Treatment: DRUG: sorafenib tosylate, DRUG: everolimus, OTHER: laboratory biomarker analysis, OTHER: pharmacogenomic studies, OTHER: pharmacological study Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Phase I only: Histologically or cytologically confirmed solid tumors that are advanced and refractory to or lack life-prolonging treatments; patients with histologically or cytologically confirmed renal cell carcinoma and hepatocellular carcinoma will be eligible * Phase II: Histologically or cytologically proven metastatic adenocarcinoma of pancreas that had progressed after one prior gemcitabine containing regimen, or progressed within 6 months of the completion of gemcitabine containing adjuvant regimen * Patients must have measurable or assessable disease * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Adequate hematological, renal and liver functions as determined by the following: * Absolute neutrophil count (ANC) > 1500 cells/mm\^3 * Hemoglobin >= 9g/dL * Platelets >= 100,000 cells/mm\^3 * Serum creatinine within institutional upper limit of normal (ULN) OR >= 60mll/min for patients with creatinine levels above institutional ULN * Bilirubin =< 1.5 x ULN * Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =< 2.5 times ULN (< 5 x ULN for patients with abnormal values attributable to liver metastases) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) =< 2.5 times ULN (< 5 x ULN for patients with abnormal values attributable to liver metastases) * International normalized ratio (INR) =< 1.5 (Anticoagulation is allowed if target INR =< 1.5 on a stable dose of warfarin or on a stable dose of low-molecular-weight (LMW) heparin for > 2 weeks at the first dose of study agent) * Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND Fasting triglycerides =<2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication * Ability to understand and willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures * Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment * Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; men should use adequate birth control for at least three months after the last administration of sorafenib and everolimus Exclusion Criteria: * Phase II: Patients in whom histological or cryological diagnosis is not consistent with adenocarcinoma including adenosquamous, islet cell, cystoadenoma or cystadenocarcinoma, carcinoid, small or large cell carcinoma or lymphoma * Phase II: Adenocarcinoma arising from a site other than the pancreas (distal bile duct, ampulla of vater or periampullary duodenum) * Prior therapy with approved or investigational agents within 4 weeks prior to the start of treatment plan in this protocol * Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN * Any active infections * Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management * Cerebrovascular accident including transient ischemic attacks within the past 6 months * Pulmonary hemorrhage/bleeding event >= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug * Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks of first dose of study drug * Serious non-healing wound, ulcer, or bone fracture * Known or suspected allergy to sorafenib, everolimus, other rapamycins (sirolimus, temsirolimus), their excipients, or any agent given in the course of this trial * Any condition that impairs patient's ability to swallow whole pills * Any malabsorption problem * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of first study drug * Urine protein:creatinine ratio >=1.0 at screening * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of baseline * Inability to comply with study and/or follow-up procedures * History of concurrent malignancy or history of a second malignancy within the past 5 years * Unable to provide informed consent * Concomitant use of any medications or substances that are inhibitors or inducers of CYP3A enzyme, which include but not limited to phenytoin, carbamazepine, barbiturates, rifampin, Phenobarbital or St. Johns Wort * Phase II: Prior treatment with mTOR inhibitors (e.g., sirolimus, temsirolimus, everolimus) or Ras-MAPK inhibitors (e.g., sorafenib) * Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy (except alopecia) * Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed * Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus (Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines) * Severely impaired lung function as defined as spirometry and diffusing capacity of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air; patients are not required to undergo mandatory respiratory function tests at screening to be eligible unless medically necessary * Severe and/or uncontrolled non-malignant liver disease such as cirrhosis or severe hepatic impairment defined as Child-Pugh class C * A known history of human immunodeficiency virus (HIV) seropositivity * Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception * Women of childbearing potential (WOCBP) that have a positive urine or serum pregnancy test within 7 days prior to the start of treatment * Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment

Study Objectives GATE 1 is an open-label, non-comparative, multicentric study evaluating the efficacy and tolerance of the combined use of Gemcitabine, Trastuzumab and Erlotinib as a first-line chemotherapy in metastatic pancreatic cancer patients. The patients will be treated intravenously with Gemcitabine at a dose of 1000 mg/m2 for 30 min. For the first eight weeks, Gemcitabine will be administered once weekly for 7 weeks followed by one week of rest. Subsequently, Gemcitabine will be administered once weekly for three weeks followed by one week of rest. Trastuzumab will be administered once a week at a dose of 4 mg/kg over 90 min. at D1 and then at 2 mg/kg over 30 min. for the subsequent infusions. Erlotinib will be administered orally at a dose of 100 mg/day from C1D1. The patients will be subjected to research for the EGFR, HER2 and KRAS status. Conditions: Metastatic Pancreatic Adenocarcinoma Intervention / Treatment: DRUG: Gemcitabine - Trastuzumab - Erlotinib Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Metastatic pancreatic adenocarcinoma confirmed by histology * Tumor sample available * Measurable lesion according to RECIST criteria * Performance status ≥ 1 * Life expectancy > 3 months * Hematology: Hb ≥ 9g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3 * Renal function: creatinine ≤ 1.5 x ULN * Hepatic function: total bilirubin ≤ 2.5 x ULN, transaminases ≤ 5 x ULN * Left ventricular ejection fraction (LVEF) ≥ 50% * At least a 6-month delay between the end of any previous gemcitabine-based chemotherapy and diagnosis of metastases * Social security * Informed consent obtained prior to inclusion. Exclusion Criteria: * Non metastatic advanced local disease * Presence of cerebral metastases or symptomatic leptomeningeal carcinomatosis * Others cancers except BBC and cervical cancer receiving curative treatment * No previous treatment by Erlotinib or Trastuzumab * Known severe hypersensitivity to Erlotinib, Trastuzumab, murine proteins or Gemcitabine * Presence of significant co-morbidities * Concomitant treatment with other experimental products or other anticancer therapies * Breastfeeding or pregnant female, or patient of reproductive age not using adequate contraception * Legal incapacity or limited legal incapacity

Study Objectives The general objective of this observational study is identify and describe the type, frequency, and severity of sexual dysfunction in patients with lung cancer and generate strategies for clinical management and oncological follow-up directed and based on the specific findings in this population. The recruitment will be carried out from July 2023 and will be carried out until December 2023, the analysis of the information will be carried out from January to March 2024. Conditions: Lung Cancer, Sexual Dysfunction Intervention / Treatment: DRUG: Systemic oncological treatment Location: Portugal, Peru, Spain, Colombia, Argentina Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age greater than or equal to 18 years and less than or equal to 70 years. * Diagnosis of lung cancer stages IB to IV. * Having received systemic oncological treatment for at least 3 months or being in oncological follow-up after having received systemic treatment for a minimum of 3 months with stable tumor disease or partial or complete response in images. * ECOG ≤ 2 Exclusion Criteria: * Patients with comorbidities (renal failure, cardiovascular diseases or similar) not controlled with corresponding medical management. * Individuals with physical disability or cognitive impairment that prevents them from completing the electronic data collection form.

Study Objectives Investigate the safety and tolerability of ramucirumab (IMC-1121B) drug product (DP) in combination with paclitaxel. Conditions: Adenocarcinoma Intervention / Treatment: BIOLOGICAL: Ramucirumab (IMC-1121B ), DRUG: Paclitaxel Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma * Has an advanced or metastatic solid gastric adenocarcinoma that has failed standard therapy * Has resolution of all clinically significant toxic effects of prior therapy, surgery, treatment with an investigational agent or device, treatment monoclonal antibody or small molecule, and radiotherapy or chemotherapy. * Has adequate organ function * Eligible participants of reproductive potential (both sexes) agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and for 12 weeks after the last dose of study medication Exclusion Criteria: * Has undergone major surgery within 28 days prior to the study, or subcutaneous venous access device placement within 7 days prior to the study registration date * Has elective or planned surgery to be conducted during the trial * Has had treatment with an investigational agent or device, an antineoplastic small molecule, or antineoplastic radiotherapy or chemotherapy * Was previously treated with a chemotherapy regimen containing nitrosoureas or mitomycin C * Has had treatment with an antineoplastic monoclonal antibody within 8 weeks prior to the study registration date * Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism prior to the study registration date * Has experienced any arterial thrombotic event, including myocardial infarction, cerebrovascular accident, or transient ischemic attack, within 6 months prior to the study date * Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents. (Participants receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters International Normalized Ratio (INR) ≤ 1.5, prothrombin time (PT) and partial thromboplastin time (PTT) or - Is receiving chronic therapy with nonsteroidal anti-inflammatory agents \[Aspirin use at doses up to 325 milligrams/day (mg/day) is permitted\] * Has significant bleeding disorders, vasculitis, history of postoperative bleeding complications, hemoptysis or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to the study date * Has a history of GI perforation and/or fistulae within 6 months prior to the study date * Has symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia * Has uncontrolled arterial hypertension despite standard medical management. * Has a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to the study date * Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea * Has a serious illness or medical condition(s) * Is pregnant or lactating * Has received treatment with another investigational drug or participation in another interventional clinical trial within 28 days prior to the study date

Study Objectives The depth of neuromuscular blockade (NMB) during surgery may cause a clinical dilemma between optimal surgical conditions and the risk of postoperative residual blockade. The aim of the study is to investigate if intense NMB improves surgical conditions during operation in patients scheduled for elective open upper abdominal surgery. Conditions: Gastrointestinal Cancer Intervention / Treatment: DRUG: Group STANDARD: Rocuronium 0.6 mg/kg followed by bolus rocuronium according to standard treatment combined with saline infusion (placebo)., DRUG: Group DEEP: Rocuronium 0.6 mg/kg followed by rocuronium infusion with target level PTC 0-1 combined with bolus saline (placebo) mimicking standard treatment. Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Patients > 18 years old * Elective open upper abdominal surgery * Can read and understand Danish * Informed consent Exclusion Criteria: * Known allergy to rocuronium or sugammadex * Severe renal disease, defined by S-creatinine> 0.200 mmol/L, GFR < 30ml/min or hemodialysis * Neuromuscular disease that may interfere with neuromuscular data * Abdominal mesh with size larger than 5\*5 cm * Lactating or pregnant

Study Objectives With the conjunction of increased life expectancy and the increasing incidence of cancer with aging, older patient represent an increasing proportion of cancer patients. Increasing age is also associated with increased risk of co-morbidities as well as a decline of functional reserve of multiple organ systems, eventually leading in the context of the disease-and/or the treatment-related stress to functional deconditioning or organ failure. Surgery or complex medico-surgical procedures - that associate chemotherapy and/or radiotherapy and surgery, can be considered as one proof-of principle of such risks, since major cancer surgery the older population is at higher risk of morbi-mortality and unplanned hospitalization for geriatric events In order to reduce complications after surgery, prehabilitation has often been considered, and 71% of the surgeons would accept a 4 weeks delay before surgery to improve patients' outcomes if shown to be beneficial. However, the actual level of evidence depends on the interventions: high for pre-operative nutrition, but low for physical exercise, due to heterogeneous programs with often bad adherence. In addition, geriatric validated interventions, in order to prevent iatrogenic event, may be added in a multi-interventional model of intervention. Conditions: Old Injury Intervention / Treatment: BEHAVIORAL: standardized geriatric intervention Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: HEALTH_SERVICES_RESEARCH Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patient ≥70 year old OR patient ≥60 years with significant comorbid condition (modified Charlson index≥3) or disability (ADL score<6/6); * Histologically or cytologically proven cancer. * Life expectancy > 3 months. * Written informed consent obtained * Covered by a Health System where applicable. Exclusion Criteria: * Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. * Patient unable to be regularly followed for any reason (geographic, familial, social, psychologic). * Any mental or physical handicap at risk of interfering with the appropriate treatment. * Any administrative or legal supervision where applicable

Study Objectives The primary objective of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of unesbulin in combination with dacarbazine for the treatment of advanced LMS and determine the overall safety profile of unesbulin in combination with dacarbazine. This study will employ the time-to-event continual reassessment method (TITE-CRM) for dose finding. Treatment will be initiated at dose level 2 (DL2) (Dacarbazine 1000 milligrams per square meter \[mg/m\^2\] intravenously \[IV\] every 21 days in combination with unesbulin 200 milligrams \[mg\] orally twice weekly) for the first participant. This dose level represents the investigator's best assessment of the MTD based on available toxicity data for both agents. For subsequent participants, the dose level at which treatment is initiated will be selected based on the TITE-CRM using the most up to date dose-limiting toxicity (DLT) information from all participants previously treated. To enroll additional participants at the RP2D, the study is amended to include an expansion cohort of up to 12 participants (some of whom could be ongoing participants who reconsent). Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason. Conditions: Leiomyosarcoma Intervention / Treatment: DRUG: Unesbulin, DRUG: Dacarbazine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed consent of an Institutional Review Board (IRB)-approved informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (if appropriate). * Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions. * Disease Status including all of the following: 1. Histological or cytological confirmation of LMS arising at any anatomic site. 2. Advanced (metastatic) or locally advanced unresectable disease. 3. Ineligible for other high-priority national or institutional study. 4. Measurable disease per RECIST v1.1 criteria. Demographics: * Age greater than or equal to (>=) 18 * Male and Female Performance Status: * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Hematopoietic: * Absolute neutrophil count (ANC) count >= 1,500/cubic millimeters (mm\^3) without the use of growth factors in the past 7 days; * Platelet count >=100,000/mm\^3 without platelet transfusion in the past 5 days; * Hemoglobin >=9 grams per deciliter (g/dL) (packed red blood cell transfusion is allowed). Hepatic: * Bilirubin lesser than (<) upper limit of normal (ULN); * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <1.5 times ULN; * Participants with liver metastases may be enrolled. Pulmonary: * Participants with well-controlled asthma (for example Use of rescue medications <2 times/week over the last 12 months) or Chronis Obstructive Pulmonary Disease (COPD) (for example no exacerbations over the prior 3 months) may be enrolled. Renal: * Creatinine <1.5 times normal, or creatinine clearance greater than (>) 45 milliliters per minute (mL/min). Prior Therapies: * Toxicity from prior therapies recovered to Grade lesser than or equal to (<=) 1 or participant's baseline, except for alopecia. In addition, endocrinopathies associated with prior immunotherapy based treatments which are well controlled on replacement medication are not exclusionary * Chemotherapy: a. Up to and inclusive of 4 prior systemic cytotoxic oncology therapy regimens for metastatic, locally recurrent, or unresectable LMS, with the last dose of prior therapy administered no fewer than 30 days or 5 times the drug half-life prior to screening. Note: prior treatment with non-cytotoxic therapy regimens (for example targeted therapies, hormonal therapies, or tyrosine kinase inhibitors) are not considered cytotoxic oncology therapies. Surgery: * At least 4 weeks since prior surgery and recovered in opinion of investigator. Other: * Capable of swallowing oral medication. * Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. * Males and females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation. Note: The Definition of effective contraception will be based on the judgement of the Principal Investigator (PI) or Designee. Exclusion Criteria: Participants meeting any of the following criteria will not be eligible for enrollment: * Received any systemic anticancer therapy including investigational agents <=3 weeks prior to initiation of study treatment. Additionally, Participants may have not received radiation <= 3 weeks prior to initiation of study treatment. * Co-existing active infection or any co-existing medical condition likely to interfere with study procedures, including: a. Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on electrocardiogram (ECG), marked baseline prolongation of QT/QTc (corrected QT interval) interval, for example, repeated demonstration of a QTc interval >500 milliseconds (msec) (Long QT Syndrome \[congenital\]). * Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) positivity. * History of solid organ transplantation. Therapeutics: * Known or suspected allergy or immediate or delayed hypersensitivity to unesbulin or dacarbazine or any agent given in this study. Gastrointestinal: * Bowel obstruction, malabsorption, or other contraindication to oral medication. * Gastrointestinal disease or other condition that could affect absorption. * Active peptic ulcer disease. * Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis. * Any condition that impairs participant's ability to swallow oral medications. Wounds /Surgery: * Serious non-healing wound, ulcer, or bone fractures. * Major surgery, open biopsy or significant traumatic injury which has not recovered in the opinion of the investigator, within 28 days of baseline. * Mucosal or internal bleeding. Concomitant Medications: * Concomitant strong CYP1A2 inhibitors (like selective serotonin reuptake inhibitor \[SSRI\] agents fluvoxamine and fluoxetine) should be avoided. CYP1A2 inhibitors may inhibit the conversion of dacarbazine to its active metabolite and may increase the exposure of unesbulin. Other: * Prior malignancies other than LMS, that required treatment or have shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to initiation. Cancer treated with curative intent more than 5 years previously and without evidence of recurrence is not an exclusion. * Known coagulopathy or bleeding diathesis. Participants on anti-coagulation should be monitored closely and International Normalized Ratio (INR) within normal range. * Prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results. * History of brain metastases or leptomeningeal disease at any time in participant's history, including treated central nervous system (CNS) disease which is clinically and radiographically stable.

Study Objectives RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy, with or without cisplatin, may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with carboplatin and paclitaxel followed by radiation therapy, with or without cisplatin, works in treating patients with metastatic head and neck cancer. Conditions: Head and Neck Cancer Intervention / Treatment: BIOLOGICAL: Cetuximab, DRUG: Carboplatin, DRUG: Paclitaxel, PROCEDURE: Conventional Surgery, RADIATION: Radiation Therapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histological proof (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. * Patients should have stage IV disease, stage T0-4 N2b/2c/3 M0 (for nasopharynx patients, stage N1 disease is eligible). Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) is required. * Patients with stage Tx primary disease are eligible if there is N2b/3 adenopathy. * Karnofsky performance status of >= 80 or Eastern Cooperative Oncology Group (ECOG) point scale 0-1 * Age > 16 years * Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of > 1500 cells/mm3 and platelet count of > 100,000 cells/mm3; adequate hepatic function with bilirubin <= Upper Limit of Normal (ULN), aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) may be up to 2.5 times the upper limit of normal if alkaline phosphatase is normal. Alkaline phosphatase may be up to 4\* ULN if SGPT and SGOT are normal. Patients who have both SGPT and SGOT > 1.5 ULN and alkaline phosphatase > 2.5 \* ULN are not eligible. Normal PT/PTT and normal serum calcium (without intervention) are required. * Creatinine clearance > 40 ml/min determined by 24 hour collection or nomogram: CrCl male = (140 - age) times (weight in kg)/serum Cr times 72 CrCl female = 0.85 times (CrCl male) * Patients should have no serious acute or chronic co-morbid condition, or acute infection. * Patients must sign a study-specific informed consent form. Exclusion Criteria: * Histology other than squamous cell carcinoma. * Evidence of distant metastases (below the clavicle) by clinical or radiographic means. * Karnofsky performance status < 80 or ECOG>1 * Prior chemotherapy, within the previous 3 years. * Prior radiotherapy to the head and neck. * Prior cetuximab therapy, prior therapy with any other drug that targets the EGFR pathway, or prior therapy with a murine or chimeric monoclonal antibody. * Initial surgical resection rendering the patient clinically and radiologically disease free. * Simultaneous primary invasive cancers. * Patients with another malignancy (excluding non melanoma skin cancers, and cancers treated > 3 years prior for which patient remains continuously disease free). * Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the study. Subjects who are men must also agree to use effective contraception. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 72 hours prior to the start of study medication. * WOCBP using a prohibited contraceptive method. * Women who are pregnant or breastfeeding. * Women with a positive pregnancy test on enrollment or prior to study drug administration. * Refusal to sign the informed consent. * Pre-existing peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or worse.

Study Objectives This phase I trial studies the side effects and best dose of hydroxychloroquine when given together with cyclophosphamide, dexamethasone, and sirolimus in treating patients with multiple myeloma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as hydroxychloroquine, may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Giving hydroxychloroquine together with sirolimus, cyclophosphamide, and dexamethasone may be a better treatment for multiple myeloma. Conditions: Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma Intervention / Treatment: DRUG: Cyclophosphamide, DRUG: Dexamethasone, DRUG: Hydroxychloroquine, OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study, DRUG: Sirolimus Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed multiple myeloma * Documented relapse or persistent disease after at least 1 prior therapy containing both bortezomib and lenalidomide; or at least 2 prior therapies containing bortezomib in one and lenalidomide in the other, or if intolerant of bortezomib and/or lenalidomide; prior autologous and allogeneic bone marrow transplantation are allowed * Need for further treatment for myeloma, as determined by the patient's treating physician; this is defined as progression of clinical features (worsening anemia, renal function, bone disease, hypercalcemia, recurrent infections, and constitutional symptoms) OR biochemical progression (increasing M-spike in serum or urine, involved serum or urine free light chain over 2 consecutive time points greater than 4 weeks apart) * Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) * Ability to understand and the willingness to sign a written informed consent document * Birth control is required with full barrier contraceptives or complete abstinence for the duration of time receiving therapy and for 6 months after completing the last drug taken * The need for further treatment: this is defined as progression of clinical features (worsening anemia, renal function, bone disease, hypercalcemia, recurrent infections, and constitutional symptoms) OR biochemical progression (increasing M-spike in serum or urine, involved serum or urine free light chain over 2 consecutive time points greater than 4 weeks apart) Exclusion Criteria: * History of allergic reactions to compounds of similar chemical or biological composition to rapamycin or hydroxychloroquine * Patients may not take any of the following medications while on study, but will be considered eligible if medication is discontinued at least 72 hours (hrs) prior to first dose of Rapamycin: * Carbamazepine * Rifabutin * Rifampin * Rifapentine * St. John's wort * Clarithromycin * Cyclosporine * Diltiazem * Erythromycin * Itraconazole * Fluconazole * Ketoconazole * Telithromycin * Verapamil * Voriconazole * Posaconazole * Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis (well-controlled psoriasis allowed provided under the care of a specialist who agrees to monitor the patient for exacerbations) * Absolute neutrophil count (ANC) =< 1.0 x 10\^9/L * Platelets =< 50 x 10\^9/L for any reason * Serum creatinine >= 2.5 mg/dL * Total or direct bilirubin >= 2.0 mg/dL * Transaminases 2 x the upper limit of normal * Fasting glucose >= 200 mg/dL * Serum potassium < 3.4 mmol/l * Serum phosphorus < 2.4 mg/dl * Other conditions that would require therapy with hydroxychloroquine, including but not limited to, any of the following: * Systemic lupus * Rheumatoid arthritis * Porphyria cutanea tarda * Malaria treatment or prophylaxis * Evidence of other active malignancy, except: * Basal cell or squamous cell carcinoma of the skin * Treated carcinoma in situ * Uncontrolled intercurrent illness including, but not limited to, any of the following: * Uncontrolled ongoing infection * Human immunodeficiency virus (HIV) * Hepatitis B infection * Known glucose-6-phosphate dehydrogenase (G6PD) deficiency * Symptomatic congestive heart failure * Unstable angina pectoris * Uncontrolled cardiac arrhythmia * Psychiatric illness or social situations that would limit compliance with study requirements * Active graft-versus-host disease (GvHD) * Inability to understand or unwillingness to sign the informed consent document * Concurrent anti-myeloma therapy within: * 7 days of prior corticosteroids * 14 days of prior antimyeloma agents, including thalidomide or lenalidomide * 28 days of a different investigational regimen * 14 days of any radiation * Women of child-bearing who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 30 days after the last dose of study drug * Women who are pregnant or breastfeeding * History of G6PD deficiency * Known history of HIV infection

Study Objectives The goal of the pilot study is to determine if a multicenter prospective cohort study of cancer patients with blood clots associated with catheters is feasible. Cancer patients with catheter-related thrombosis treated with one month of anticoagulation will be evaluated for for post-thrombotic syndrome. Laboratory biomarkers will be evaluated as predictors of recurrent thrombosis. Conditions: Venous Thrombosis, Neoplasms Intervention / Treatment: DRUG: Heparin, Low-Molecular-Weight, or direct oral anticoagulants Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: HEALTH_SERVICES_RESEARCH Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Upper extremity venous thrombosis associated with an indwelling catheter documented by ultrasound, CT or venography * Current hematologic or solid tumor malignancy undergoing chemotherapy, surgery, radiation or hormonal therapy for malignancy. * >18 years of age * Platelet count >50,000 * Creatinine clearance >30 ml/min * Ability to provide informed consent Exclusion Criteria: * Underlying medical condition or chemotherapy requiring long-term anticoagulation * Known underlying higher risk thrombophilias including antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiencies, or homozygosity or compound heterozygosity for prothrombin G20210A or Factor V R506Q mutations. * Inability to remove venous catheter * Anticipated replacement of central venous catheter within 3 months * Major bleeding or clinically relevant non-major bleeding in the preceding 60 days * Participation in another clinical trial that requires anticoagulation * Use of anticoagulant other than low-molecular weight heparin * Treatment with thrombolysis * Catheter removal >1 month prior to enrollment

Study Objectives The purpose of this study is to compare hemostasis, ovarian function preservation effect, and safety about intraoperative bleeding with SurgiGuard@ in women who underwent laparoscopic unilateral ovarian cystectomy Conditions: Ovarian Cyst Benign Intervention / Treatment: DRUG: Surgiguard Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Female, 18 years ≤ Ages <45 years * laparoscopic unilateral ovarian cystectomy scheduled patients with benign unilateral ovarian cyst confirmed by ultrasonography * women with regular menstruation * women with regular menstruation cycle from 21 days to 45 days * Proper state for laparoscopic operation (American society of Anesthesiologists Physical Status classification 1 or 2) * Patients who signed and approved informed consent Exclusion Criteria: * Patients without ovarian cyst * Patients with malignant female genital disease * Patients with bilateral ovarian cysts * Age ≥ 45 * Pregnancy or lactating women * Serum AMH<0.05 ng/ml * Patients with endocrine disease such as thyroid abnormality, hyperprolactinemia, cushing disease, etc * Patients with hormone replacement therapy during 3 months * Patients who is considered to be difficult to perform the clinical trial when researchers judge

Study Objectives RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia. PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia Conditions: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Acute Myeloid Leukemia/Transient Myeloproliferative Disorder, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Childhood Acute Myeloid Leukemia in Remission, Childhood Myelodysplastic Syndromes, de Novo Myelodysplastic Syndromes, Myelodysplastic Syndrome With Isolated Del(5q), Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes Intervention / Treatment: RADIATION: total-body irradiation, PROCEDURE: allogeneic hematopoietic stem cell transplantation, DRUG: cyclophosphamide, DRUG: mycophenolate mofetil, DRUG: busulfan, DRUG: cyclosporine, DRUG: fludarabine phosphate, PROCEDURE: peripheral blood stem cell transplantation, PROCEDURE: nonmyeloablative allogeneic hematopoietic stem cell transplantation, OTHER: laboratory biomarker analysis, GENETIC: cytogenetic analysis, OTHER: flow cytometry, GENETIC: fluorescence in situ hybridization, OTHER: pharmacological study, GENETIC: polymorphism analysis, DRUG: tacrolimus, DRUG: methotrexate Location: United States, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Myelodysplastic syndrome (MDS) or transformed acute myelogenous leukemia (transformed from MDS) * De novo acute myelogenous leukemia (AML) beyond first remission * Intermediate or high risk de novo AML in first complete response (at FHCRC unrelated donor recipients only) * Chemotherapy required prior to HCT for all patients: * A) Interval between start of a cycle of cytoreductive chemotherapy and infusion of donor stem cells must be at least 30 days; chemotherapy received for disease maintenance will be allowed during this time period * B) All patients must have < 5% myeloblasts based on marrow morphology performed within 21 days prior to start of conditioning regimen and at least 3-4 weeks after the start of pre-transplant cytoreductive chemotherapy * C) All patients must have no circulating peripheral blood myeloblasts present based on morphologic analysis * Age 65 years or under for patients with related donors; age 60 years or under for patients with unrelated donors * HCT-Specific Comorbidity Index Score (HCT-CI) < 3 * Related donor (age > 12 years, nonsyngeneic) or unrelated donor, HLA phenotypically or genotypically identical at the allele level at A,B,C,DRQ1, and CBQ1 * DONOR: Related or unrelated donors who are genotypically or phenotypically matched by high resolution HLA typing (HLA-A, B, C, DRB1, and DQB1); class 1 single allele mismatch allowed * DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A\*0101 and the donor is A\*0201, and this type of mismatch is not allowed * DONOR: A positive anti-donor cytotoxic crossmatch or flow cytometric assay is an absolute donor exclusion at FHCRC/SCCA * DONOR: Age >= 12 years * DONOR: Donors must consent to PBSC mobilization with G-CSF and leukaphereses; bone marrow as a source of stem cells will not be allowed * DONOR: Donor must have adequate veins for leukaphereses or agree to placement of central venous catheter (femoral, subclavian) Exclusion Criteria: * HIV seropositivity * Fungal infections with radiographic progression after appropriate therapy for greater than one month * Organ dysfunction * Symptomatic coronary artery disease or ejection fraction < 35% * DLCO < 65%, FEV1 < 65% or receiving supplementary continuous oxygen * Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded * Karnofsky Performance Score < 70 * Lansky-Play Performance Score < 70 for pediatric patients * Life expectancy severely limited (< 2 years) by disease other than MDS/AML * Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment * Patients with active non-hematological malignancies except: * A) Patients with follicular or low grade lymphoma will be eligible as long as they have not and do not require active treatment for control of their disease * B) Patients with localized non-melanoma skin malignancies * Patients with poorly controlled hypertension who are unable to have blood pressure stabilized below 150/90 mm Hg on standard medication * Females who are pregnant or breastfeeding * Patients with systemic, uncontrolled infections * Active CNS disease as identified by positive CSF cytospin * DONOR: Identical twin * DONOR: Age < 12 years * DONOR: Pregnancy * DONOR: HIV seropositivity * DONOR: Inability to achieve adequate venous access * DONOR: Known adverse reaction to G-CSF

Study Objectives Defects in the apoptotic process can lead to the onset of cancer by allowing cells to grow unchecked when an oncogenic signal is present. Obatoclax is designed to restore apoptosis through inhibition of the Bcl-2 family of proteins, thereby reinstating the natural process of cell death that is often inhibited in cancer cells. Conditions: Lymphoma, Follicular Intervention / Treatment: DRUG: Obatoclax mesylate, DRUG: Rituximab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Pathological confirmation of Follicular Lymphoma (FL) * Must have advanced stage disease * Must not have received any prior chemotherapy or immunotherapy for lymphoma, including steroids * Must have adequate organ function * Must have the ability to understand and willingness to sign a written informed consent form Exclusion Criteria: * No other agents or therapies administered with the intent to treat malignancy * Uncontrolled, intercurrent illness * Pregnant women and women who are breast feeding

Study Objectives This 2 arm study will compare the efficacy and safety of Avastin plus Herceptin/docetaxel, versus Herceptin/docetaxel alone, in patients with HER2 positive locally recurrent or metastatic breast cancer who have not received prior chemotherapy for their metastatic disease. Patients will be randomized 1:1 to receive either Avastin (15mg/kg iv q3weeks) + Herceptin (8mg/kg iv loading dose and 6mg/kg iv q3weeks maintenance) + docetaxel (100mg/m2 iv q3weeks) or Herceptin + docetaxel alone. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals. Conditions: Breast Cancer Intervention / Treatment: DRUG: bevacizumab [Avastin], DRUG: Docetaxel, DRUG: Herceptin Location: Mexico, Canada, Czech Republic, Turkey, Italy, Brazil, Romania, Spain, United Kingdom, Australia, Uruguay, Austria, Bosnia and Herzegovina, Argentina, Russian Federation, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * adult patients, >=18 years of age; * HER2 positive breast cancer with locally recurrent or metastatic lesions; * eligible for chemotherapy; * baseline LVEF >=50%. Exclusion Criteria: * previous chemotherapy for metastatic or locally recurrent breast cancer; * previous radiotherapy for metastatic breast cancer (except for metastatic bone pain relief); * other primary tumor within last 5 years, with the exception of basal or squamous skin cancer, or in situ cancer of the cervix; * clinically significant cardiovascular disease; * chronic daily treatment with aspirin (>325mg/day) or clopidogrel (>75mg/day).

Study Objectives To evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a potential rituximab biosimilar) in patients with CD20-positive B-cell lymphomas. Conditions: B-cell Lymphomas Intervention / Treatment: DRUG: HLX01 Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * 18 years ≤ aged ≤ 65 years, male or female; * having histologically confirmed diagnosis of relapsed/refractory CD20-positive B-cell lymphomas which needed consolidation therapy; * Eastern Cooperative Oncology Group (ECOG) performance status≤1 and life expectancy ≥3 months; * providing signed and dated informed consents. Exclusion Criteria: * Usage of rituximab or other anti-CD20 monoclonal antibody within 2 years before enrollment; * usage of hematopoietic cytokines within 1 week before enrollment, e.g. granulocyte colony stimulating factor (G-CSF); * recent major surgery (excluding diagnostic surgery) within the past 8 weeks; * peripheral nervous system diseases or central nervous system diseases; * inadequate hematologic function met any of the following at screening: white blood cell count <3.0×109/L, absolute neutrophil count (lobocyte and rhabdocyte) <1.5×109/L, platelet count <100×109/L, hemoglobin <90 g/L, for patients with bone marrow involvement, absolute neutrophil count (lobocyte and rhabdocyte) <1.0×109/L, platelet count <75×109/L, hemoglobin <80 g/L; * inadequate liver function met any of the following at screening: total bilirubin>1.5×the upper limit of normal range (ULN), ALT or AST>2.0×ULN, alkaline phosphatase (ALP)>3.0×ULN; * abnormal renal function (serum creatinine>1.5×ULN); * abnormal thyroid function (TSH< lower limit of normal or > upper limit of normal with clinical significance judged by investigators); * positive test result(s) for serum HIV antigen or antibody; * seropositivity of HBsAg, or seropositivity of HBcAb and HBV DNA>ULN; seropositivity of Anti HCV antibody; * history of herpes zoster and left with sequelae or latent infection; * other serious disease which may restrict subjects to participate in the trial (such as ongoing active infection, uncontrolled diabetes mellitus, severe cardiac insufficiency or angina pectoris, gastric ulcer, active autoimmune disease, etc.); * pregnancy or breast feeding female, or not willing to use effective contraceptive measures during the study; * allergic constitution, or known allergic to components of rituximab or other anti-CD20 monoclonal antibody; * history of alcoholism or drug abuse; participation in other clinical trials within 3 months before enrollment; * not suitable for enrollment at investigator's discretion.

Study Objectives The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with other anticancer agents in participants with advanced or metastatic solid tumors. Conditions: Solid Tumor, Breast Cancer, Colon Cancer, Cholangiocarcinoma, Soft Tissue Sarcoma Intervention / Treatment: DRUG: LY3039478, DRUG: Taladegib, DRUG: Abemaciclib, DRUG: Cisplatin, DRUG: Gemcitabine, DRUG: Carboplatin, DRUG: LY3023414 Location: Denmark, United States, Spain, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer. * For dose escalation for all combinations: The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic. * For Part A dose confirmation: All participants must have histological evidence of advanced or metastatic soft tissue sarcoma or breast cancer. Breast cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. * For Part B dose confirmation: All participants must have histological evidence of advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. * For Part C dose confirmation: All participants must have histological evidence of advanced or metastatic breast cancer and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. * For Part D dose confirmation: All participants must have histological evidence of cholangiocarcinoma and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >1 line of prior systemic therapy for metastatic or resectable disease (that is, participants may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease). * For Part E dose confirmation: All participants must have histological evidence of locally advanced or metastatic triple negative breast cancer (TNBC) and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >2 lines of systemic treatment for advanced or metastatic TNBC. * Have adequate organ function. * Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Have discontinued all previous therapies for cancer. Exclusion Criteria: * Have current acute leukemia. * Have current or recent (within 3 months of study drug administration) gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.

Study Objectives The purpose of this study is to assess the long-term safety profile and the secondary objective to estimate clinical benefit of ZD1839 (gefitinib). Conditions: Lung Cancer, Breast Cancer Intervention / Treatment: DRUG: Gefitinib Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Provision of written informed consent to participate in the trial. * Female or male aged 18 years and over. * Patients with previously diagnosed cancer who have been treated with ZD1839 in a parent ZD1839 clinical trial and may benefit from continuation Exclusion Criteria: * Known severe hypersensitivity to ZD1839 * Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort. * Withdrawal from a parent ZD1839 trial because of tumor progress

Study Objectives There is an unsatisfied medical need for a first-line treatment of lymphatic malformations with a good benefit/risk profile. Based on a patient experience in the institution, the investigators plan to verify whether or not the medication sildenafil has a beneficial effect on lymphatic malformations. The investigators plan to do this by treating patients with lymphatic malformations with the medication sildenafil for a 20 week period. This is an investigator initiated study funded by an Innovations in Patient Care grant and a SPARK grant. Conditions: Lymphangioma Intervention / Treatment: DRUG: Sildenafil Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written informed consent(s) for study participation and (where applicable) the use of the participant's images are obtained according to national regulations from the participant's parent(s) or guardian(s) prior to performing any study procedures. * The participant is 6 months to 10 years of age at inclusion. * The participant weight is at least 8kg. * A diagnosis of LM or mixed venous lymphatic malformation involving the skin and subcutaneous tissue and at least 3cm based on clinical and radiographic criteria. * LMs may benefit from systemic therapy based on clinical criteria. * Females must not be pregnant or breast-feeding. * If participant is a child, parent/guardian must be able to follow instructions and must be willing and able to ensure that the subject is present for all required study visits. * Subject has no contraindication for use of sildenafil. * LMs may involve any part of the body. * Subject will have normal results on screening tests (eye exam, blood tests). * Subject has no contraindication for MRI examinations, such as metal implants, etc. * Subject must not be a smoker. Exclusion Criteria: * The participant has a medically unstable health status that may interfere with his/her ability to complete the study. * The participant presents with one or more of the following medical conditions: hepatic impairment; severe renal impairment; lymphedema conditions such as Milroy disease, Meige lymphedema, Hennekam syndrome, Njolstad syndrome, Aagenaes syndrome, and Fabry disease; hypotension or at risk for hypotension; seizures or history of seizures; any significant cardiovascular risk factors and any condition which requires participants to use nitric oxide donors or nitrates in any form; underlying anatomic or vascular risk factors for developing non-arteritic anterior ischemic optic neuropathy (NAION) including low ocular cup to disc ratio, age over 10, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. (Participants with Down syndrome, Turner syndrome, and Noonan syndrome will be considered on a case-by-case basis). * The participant has received at least one of the following medications contraindicated in association with sildenafil within 15 days of inclusion: Alprostadil, Azole antifungals, Clarithromycins, Conivaptan, Delavirdine, Erythromycins, Fluvoxamine, Grapefruit, Imatinib, Nefazodone, Nitrates/sodium thiosulfate, Non-selective and selective alpha blockers, Protease inhibitors, Rufinamide, Tadalafil, Telithromycin, Vardenafil, Yohimbe, Yohimbine, Amifostine, Lapatinib, Warfarin * The participant requires concomitant use of potent cytochrome P450 3A4 inhibitors (such as ketoconazole, itraconazole, erythromycin, saquinavir) or concomitant use of ritonavir. * The patient has had extensive prior surgery or sclerotherapy to treat LM such that scarring may interfere with the treatment effect of sildenafil. * The participant has previously been administered treatment for LMs or surgical procedures have been performed to remove the index LMs. * Participant is currently pregnant or considering becoming pregnant in the next 20 weeks. * The participant is known to have an allergy to sildenafil. * Ulcerated or currently infected LMs with pain. * Diagnosis of the soft tissue tumor as LM is not clinically certain. * The participant is participating in another clinical study. * The participant has a history of priapism or is diagnosed with sickle cell anemia or any other disorder which may predispose to priapism. * The investigator may declare any subject ineligible for a valid medical reason.

Study Objectives The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough). Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Dara SC, DRUG: Dara IV Location: Israel, Canada, Japan, Korea, Republic of, Italy, Brazil, Spain, Ukraine, United Kingdom, United States, Australia, Greece, Taiwan, Czechia, Russian Federation, Sweden, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Evidence of a response (Partial response \[PR\] or better based on investigator's determination of response by international myeloma working group \[IMWG\] criteria) to at least 1 prior treatment regimen * Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to \[>=\] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day \[mg/day\] for 4 days) would not be considered prior lines of therapy * Documented multiple myeloma as defined by the criteria below: 1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria 2. Measurable disease at Screening as defined by any of the following: 1. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or 2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Meet the clinical laboratory criteria as specified in the protocol * Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization Exclusion Criteria: * Received daratumumab or other anti-CD38 therapies previously * Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) before treatment * Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing) * Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant) * History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years

Study Objectives This is a Phase 1, single-dose, open-label, dose-escalation study. The study will be conducted in three parts (i.e. regimens) in an outpatient setting as follows: * Regimen A: FATE-NK100 as a monotherapy in subjects with advanced solid tumor malignancies. * Regimen B: FATE-NK100 in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, HER2+ advanced gastric cancer or other advanced HER2+ solid tumors. * Regimen C: FATE-NK100 in combination with cetuximab in subjects with advanced colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC), or other epidermal growth factor receptor 1 positive (EGFR1+) advanced solid tumors. Conditions: HER2 Positive Gastric Cancer, Colorectal Cancer, Head and Neck Squamous Cell Carcinoma, EGFR Positive Solid Tumor, Advanced Solid Tumors, HER2-positive Breast Cancer, Hepatocellular Carcinoma, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Pancreatic Cancer, Melanoma Intervention / Treatment: DRUG: FATE-NK100, DRUG: Cetuximab, DRUG: Trastuzumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Regimen A only (monotherapy): Subjects with advanced metastatic solid tumors * Regimen B only (combination with trastuzumab): Subjects with advanced metastatic HER2+ solid tumors * Regimen C only (combination with cetuximab): Subjects with advanced metastatic EGFR+ solid tumors * Available related donor who is CMV+ and HLA-haploidentical or better but not fully HLA-matched * Presence of measurable disease by RECIST 1.1 * Life expectancy of at least 3 months. * Provision of signed and dated informed consent form (ICF). * Stated willingness to comply with study procedures and duration. Exclusion Criteria: * Females of reproductive potential that are pregnant or lactating, and males or females not willing to use a highly effective form of contraception from Screening through the end of the study. * Eastern Cooperative Oncology Group (ECOG) performance status >2. * Evidence of insufficient organ function as determined by the protocol. * Receipt of any biological therapy, chemotherapy, or radiation within 1 week of the Screening Visit and at least 3 weeks prior to Day 1, except for patients receiving maintenance trastuzumab. * Have central nervous system disease (CNS) as follows: 1. Dose Escalation Cohorts: Active CNS disease, including history of CNS metastases. 2. MTD/MFD Expansion Cohorts: CNS disease, including history of CNS metastases, that was not stable during the last 6 months. * Myocardial infarction (MI) within 6 months of Screening Visit. * Severe asthma. * Currently receiving or likely to require systemic immunosuppressive therapy from Day -7 to Day 29. * Uncontrolled infections. * Presence of any medical or social issues that are likely to interfere with study conduct, or may cause increased risk to subject.

Study Objectives This single arm study will determine the maximum tolerated dose, and recommended dose for further development, of R547, in patients with advanced solid tumors. Groups of patients will receive ascending doses of R547 as weekly intravenous infusions administered over a) 90 minutes and b) 180 minutes, on days 1 and 8 of a 21 day cycle. In the absence of dose-limiting toxicity following the starting dose, incremental dose-escalations will be allowed in subsequent cohorts of patients until the maximum tolerated dose is reached. The anticipated time on study treatment is until disease progression or dose-limiting toxicity, and the target sample size is \<100 individuals. Conditions: Neoplasms Intervention / Treatment: DRUG: RG547 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * adult patients, >=18 years of age; * locally advanced or metastatic solid tumors; * measurable or evaluable disease. Exclusion Criteria: * prior chemotherapy, radiotherapy or immunotherapy within 3 weeks of start of study; * prior history of CNS metastases with disease progression; * patients taking strong inhibitors and/or inducers of CYP3A4.

Study Objectives CI-1033 is an experimental drug that acts as an inhibitor of erbB (EGFR) receptors, which may be involved in tumor growth. The primary objective of this study is to assess the antitumor activity of CI-1033 in patients with metastatic breast cancer. Patients with histologically confirmed metastatic (Stage IV) breast cancer and who have received no more than 2 prior cytotoxic chemotherapy regimens are eligible for this study. CI-1033 is administered orally. Patients are required to have blood tests periodically while receiving treatment and will be closely monitored throughout the study for possible side effects and response to treatment. Patients may not have received any prior treatment with other agents that target erbB receptors, including Herceptin (trastuzumab) or Iressa (gefitinib). Conditions: Breast Neoplasms Intervention / Treatment: DRUG: CI-1033 Location: Canada, Italy, Spain, United Kingdom, United States, Belgium, Ireland, Sweden, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Female, at least 18 years of age * Histologically confirmed diagnosis of breast cancer * Metastatic (Stage IV) disease * Progressive or recurrent disease following the most recent therapy * No more than 2 different, prior cytotoxic chemotherapy regimens for metastatic disease * At least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) that has not been irradiated * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, determined within 2 weeks prior to randomization * Estimated life expectancy of > 12 weeks * Capable of giving written informed consent * Capable of swallowing intact CI-1033 capsules * Capable of understanding and adhering to the protocol requirements * No prior exposure to CI-1033 or other agents that target the erbB receptor family (such as Herceptin, Iressa, Tarceva, IMC-C225, and EKB-569) * No known hypersensitivity reaction to tyrosine kinase inhibitors * Adequate liver, renal, or bone marrow function determined within 2 weeks prior to randomization * No cytotoxic chemotherapy within 3 weeks prior to baseline disease assessments (6 weeks for nitrosoureas or mitomycin) * No immunotherapy (including Herceptin) or other biologic therapy within 2 weeks prior to baseline disease assessments * No hormone therapy (including hormone replacement therapy) within 4 weeks prior to baseline disease assessments (6 weeks for megestrol acetate) * Patients must have recovered from the acute effects of any radiation therapy or surgery * No treatment with any other investigational therapy within 4 weeks prior to baseline disease assessments * No history of any cancer other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix) within the last 5 years * No patients with untreated brain metastases or patients that have not recovered from treatment for brain metastases * No known malabsorption syndrome or other condition that may impair absorption of study medication * No comorbidity or condition which compromises compliance with this protocol as judged by the investigator or that would significantly complicate interpretation of the safety profile of CI-1033 * No patients having reproductive potential who are not using a method of birth control or who are pregnant or breastfeeding or have a positive pregnancy test during baseline Exclusion Criteria: Prior exposure to CI-1033 or other agents that target the erbB receptor family; cytotoxic chemotherapy within 3 weeks prior to baseline disease assessments (6 weeks for nitrosoureas or mitomycin); immunotherapy (including Herceptin) or other biologic therapy within 2 weeks prior to baseline disease assessments; hormone therapy (including hormone replacement therapy) within 4 weeks prior to baseline disease assessments; 6 weeks for megestrol acetate (to exclude the possibility of a hormone-withdrawal response); patients with untreated brain metastases.

Study Objectives Optico-chiasmatic gliomas have therapeutic feature since surgical resection plays a secondary role. Unlike other sites, many of these tumors are not amenable to complete resection either because of anatomical location, and sometimes they only can be biopsied. A substantial number of children will have recurrences following resection or will experience progression following incomplete tumor removal or biopsy. Celebrex is a Cox-2 inhibitor with anti-angiogenic and anti-tumor properties, while statins are known to increase the sensitivity of gliomas to anti-tumor agents. Their association could be administered for long periods, in the hope of much reduced risk of toxicities. This is a national, multicentric, interventional, open-label, non-comparative, and non-randomized phase I study evaluating the maximum tolerated dose of the Fluvastatin in combination with fixed-dose of Celebrex. This project involves 10 SFCE health centers accustomed to phase I / II studies(Société Française de Lutte contre les Cancers et Leucémies de l'Enfant et de l'Adolescent - French Society for the Fight against Cancer and Leukemia in Children and Adolescents). Conditions: Glioma Intervention / Treatment: DRUG: Fluvastatine, DRUG: Celebrex Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed recurrent or progressive primary hypothalamic-chiasmatic low grade glioma, and not warranting a biopsy or surgery * Histologically confirmed recurrent or progressive primary hypothalamic-chiasmatic high grade glioma, or in complete remission after a new exeresis, excepted brainstem gliomas * Relapsed or refractory disease after at least 1 line adjuvant treatment including radiation therapy, but not surgery * Measurable lesions according to RANO criteria for the patients with low grade glioma and for the patients with high grade glioma included in RP2D level (Recommended Phase 2 Dose). * Non-measurable lesions according to RANO criteria for patients with high grade glioma included in the dose escalation step. * Age > 6 years and < 21 years old * Lansky score > 70 or WHO score < 2 (neurological conditions associated with the disease should not be taken into consideration) * Haematological conditions: ANC > 1000/mm3 and platelets > 75000/mm3 * Creatinine < 1.5 x normal for age or calculated clearance > 70 ml/mn/1.73m2 * Hepatic function: Total bilirubin < 3 N and SGOT and SGPT < 4 N * Muscle enzymes : CPK < 2 N * No organ toxicity superior to grade 2 according to NCI-CTCAE v4.0 * No allergy, hypersensibility to one of the compounds of the treatment * Patients able to swallow capsules * Life expectancy at least > 6 months for low grade gliomas and > 3 months for high grade gliomas * Patient affiliated with a health insurance system * Effective contraception for patients (male and female) with reproductive potential throughout the treatment period * Written informed consent of patient and/or parents/guardians prior to the study participation Exclusion Criteria: * Chemotherapy within 21 days before D1 of experimental treatment. This period may be shortened in case of previous chemotherapy with vincristine (2 weeks), or extended in case of targeted therapies (4 weeks), or treatment by nitrosoureas (6 weeks) * Radiotherapy within 6 months before D1 of experimental treatment * Peptic ulcer disease, or gastrointestinal bleeding * Known hypersensitivity to sulfonamides. * History of asthma, acute rhinitis, nasal polyps, angioedema, urticaria or other allergic-type reactions induced by acetylsalicylic acid or NSAIDs , including COX-2 inhibitors (cyclo-oxygenase- 2) * Inflammatory bowel disease. * Known congestive heart failure (NYHA II- IV) * Ischemic proven, peripheral and/or history of arterial stroke (including transient ischemic attack) * Pregnancy or breast feeding woman * Known allergy to experimental treatment * Organ toxicity superior to grade 2 according to NCI-CTCAE v4.0 * Active infection * Pre-existing muscle pathology * Unsuitable for medical follow-up (geographic, social or mental reasons)

Study Objectives The primary purpose of the study is to determine if patients with brain metastases from non-small cell lung cancer treated with Motexafin Gadolinium and whole brain radiation therapy retain their neurologic function and ability to think for a longer time compared to patients treated with whole brain radiation therapy alone. Conditions: Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Metastases, Neoplasm Intervention / Treatment: DRUG: Motexafin Gadolinium Location: Canada, Germany, Netherlands, United States, Belgium, Australia, Austria, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Adults (≥18 years old) with radiologically proven parenchymal brain metastases from histologically confirmed non-small cell lung cancer; * KPS score of ≥70; * Each patient must sign a study-specific Informed Consent form Exclusion Criteria: * Liver metastases; * Extracranial metastases in two or more organs; * Known leptomeningeal metastases or subarachnoid spread of tumor; * Prior whole brain radiation; * Plan to use radiosurgery or radiation boost after completion of WBRT; * Planned chemotherapy during study treatment (prior and subsequent chemotherapy is allowed); * Prior total resection of a single brain metastasis; * Laboratory values as follows: LDH > 1.3 x upper limit of normal (ULN); ANC < 1500 /mm³; Platelets < 50,000 /mm³; Creatinine > 2.0 mg/dL; AST or ALT > 2 x ULN; Total bilirubin > 2 x ULN; * Women who are pregnant or lactating

Study Objectives To determine the safety and efficacy of AG-013736 in combination with other standard of care medication in patients with first line metastatic colorectal cancer. Conditions: Colorectal Neoplasms Intervention / Treatment: DRUG: bevacizumab, DRUG: AG-013726, DRUG: AG-013736 (axitinib) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * (Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment * (Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy. * Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was > 12 months prior to enrollment, * Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication. Exclusion Criteria: * Prior system therapy for advanced CRC (Ph 2 portion only) * Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors. * Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%) * Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed > 2 weeks of enrollment and be fully recovered from any procedure.

Study Objectives The purpose of this study is to determine if the combination therapy of Hormone, Paclitaxel and Radiation therapy are effective in treatment of locally advanced prostate cancer Conditions: Prostate Cancer Intervention / Treatment: DRUG: Hormone Suppressors, DRUG: Paclitaxel, RADIATION: Radiation Therapy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Any one or more of the following characteristics will qualify patient with T2/T3 prostate cancer for eligibility to current study: * Biopsy proven prostate cancer with Gleason score > 7 * Pathologic staging TXN1 (on MRI or CT) * Prostate-specific antigen (PSA) > 10 ng/ml done within a month prior to study entry (the day of first hormonal ablation) and > 10 days after prostate biopsy. In addition patients must also have: * Performance status < 2 * Hemoglobin > 11 grams per deciliter (g/dL), White blood cell (WBC) > 4000 and platelet count > 100.000/l * No evidence of other synchronous primary. Prior malignancies does not exclude if the patient is disease free > 5 years. * Prior or concurrent basal cell or non-invasive squamous carcinoma of the skin is eligible and * Received hormone therapy with any of the following combination for less than 3 months * Lupron / Flutamide * Zoladex/ Flutamide * Lupron/ Casodex * Zoladex/ Casodex Exclusion Criteria: * Clinical stage T1N0, PSA < 10, and Gleason score less than 7. * Evidence of distant metastasis * Previous surgery for prostate cancer (radical prostatectomy). * Current treatment with ketoconazole, cimetidine or hormone therapy for more than 3 months prior to inclusion in the protocol for prostate cancer * Major medical or psychiatric illness, which in the investigator's opinion may prevent completion of the study and interfere with follow up. * Bilirubin > 1.5 * Prior chemotherapy is not allowed

Study Objectives A tolerance, safety and pharmacokinetic ascending dose phase I Study of RC48-ADC administered intravenously to subjects with HER2-positive malignant in advanced malignant solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: RC48-ADC Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed informed consent form; * Aged 18-75 years; * ECOG physical condition is 0 or 1; * Life expectancy greater than 12 weeks; * Patients with locally advanced or metastatic malignant solid tumors diagnosed by pathology and refractory to standard of care therapy, or for whom no standard of care therapy is available histology standard of care therapy, or for whom no standard of care therapy is available; * Human epidermal growth factor receptor 2 (HER2)-positive refers to immunohistochemistry (IHC 2+or 3+); * Patients with measurable and appreciable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1); * Adequate organ function as defined by the following criteria: * absolute neutrophil count(ANC) >= 1.5 x 10(9)/L; * platelets>=100\*10(9)/L; * Total serum bilirubin <=1.5\*ULN; * serum aspartate transaminase (AST) and serum alanine transaminase (ALT) <=3.0\*upper limit of normal (ULN), or AST and ALT<=5\*ULN if liver function abnormalities are due to underlying malignancy; * normal serum creatinine; * international normalized ratio(INR) and activated partial thromboplastin time (aPTT) must be less than or equal to 1.5 times the upper limit of the normal range (ULN); * Women of child-bearing potential and men must agree to use adequate contraception (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete sexual abstinence, or sterilized partner) prior to study entry and during the period of therapy and for 30 days after the last dose of study drug; * Left ventricular ejection fraction (LVEF) >= 50% as assessed by echocardiogram. Exclusion Criteria: * Current pregnancy or lactation; * Serologic status reflecting active hepatitis B or C infection; * Major surgery within 4 weeks of first dose of study drug and not fully recovered * Receiving palliative radiation therapy for bone metastases if administered <= 2 weeks prior to first study treatment; * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade less than or equal to1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia; * Prior-treatment with other clinical research anticancer drugs within 28 days before study drug treatment; * The active infection with clinical significance According to the researcher's judgment, * Known history of immune deficiency,including HIV-positive or other known acquired or congenital immunodeficiency, or organ transplantation; * Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or greater than or equal to Class 2 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction unstable angina, or acute coronary syndrome within 6 months prior to enrollment in the study; * Unwilling or unable to participate in all required study evaluations and procedures; * The time interval which is from the last chemotherapy or HER2 targeted therapy until the first trial is more than 21 days; * Patients who had received systemic steroid therapy for a long time (Patients who had received systemic steroid therapy for short time and stopped drug more than 2 weeks could be enrolled); * Serious complications such as active alimentary tract hemorrhage, intestinal obstruction, enteroparalysis, interstitial pneumonia, pulmonary fibrosis, renal failure, glaucoma and uncontrolled diabetes; * Uncontrolled primary or metastatic tumor of brain; * Current peripheral neuropathy of Grade ≥ 2; * History of nerve or psychiatric disorders.

Study Objectives The main purpose of this study is to learn if adding the investigational drug RO7009789 (anti-CD40) to nab-paclitaxel and gemcitabine both before surgery and after surgery is safe, feasible, and beneficial to patients with pancreatic cancer. This study also intends to look at blood and tissue samples to help doctors better understand the role of the immune system in fighting cancer. Conditions: Pancreatic Cancer Intervention / Treatment: DRUG: RO70097890, DRUG: nab-paclitaxel, DRUG: gemcitabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL

Inclusion Criteria: * Histological documentation of primary adenocarcinoma of the pancreas * Surgically eligible for tumor resection with curative intent * Age ≥18 years * ECOG PS 0 or 1 * Adequate bone marrow function (ANC ≥1,500; Hgb >9; Plt >100) * Adequate renal function (Cr <1.5 ULN) * Total bilirubin ≤1.5 x ULN; and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN (values post biliary stenting allowed for eligibility). * Signed, written informed consent Exclusion Criteria: * Non ductal adenocarcinomas, neuroendocrine neoplasms, cystic tumors of the pancreas such as cystadenomas, cystadenocarcinomas and solid pseudopapillary neoplasms. In addition, adenocarcinomas arising from duodenum, distal bile duct, and ampulla will also be excluded. * Patients with M1 disease or a history of M1 disease. * Patients with any type of recurrent pancreatic adenocarcinoma * Prior therapy such as chemotherapy or radiation therapy or anti-tumor experimental therapy for pancreatic cancer * Previous treatment with any other compound that targets CD40 * Concurrent treatment with any anticancer agent outside of this protocol * Prior allogeneic bone marrow transplant * History of autoimmune disorder, including type 1 diabetes mellitus, pemphigus vulgaris, systemic mastocytosis, systemic lupus erythromatosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic sclerosis, Sjörgen's syndrome, vasculitis/arteritis, Behcet's syndrome, autoimmune thyroiditis, multiple sclerosis, or uveitis,. (Vitiligo is allowed) * History (within the previous year) of stroke or transient ischemic attack, unstable angina, myocardial infarction, congestive heart failure * History of deep venous thrombosis or migratory thrombophlebitis (Trousseau); * Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrand disease, or cancer-associated DIC) * Prior allergic reactions attributed to other monoclonal antibodies * Concurrent or planned concurrent treatment with systemic high dose (immunosuppressive) corticosteroids or treatment with systemic corticosteroids within 4 weeks of baseline * Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial * Concurrent or planned concurrent treatment with anticoagulants such as Coumadin or heparin, except to maintain patency of in-dwelling catheters * Ongoing or active infection; treatment with systemic antibiotics or antifungals for ongoing or recurrent infection (topical use of antibiotics or antifungals is allowed) * Pregnancy or breast-feeding - female patients must be surgically sterile, be post-menopausal, or must agree to use effective contraception during the period of therapy and for 90 days following the last dose of RO7009789. All female patients with reproductive potential must have a negative pregnancy test prior to enrollment. Women or men of reproductive potential may not participate unless they agree to use an effective contraceptive method. Female patients should not become pregnant while participating in this research study or for 90 days following therapy. Male patients should not father a child while in this research study or for 90 days following therapy. * Other uncontrolled, concurrent illness that would preclude study participation; or, psychiatric illness or social challenges that would entail unreasonable risk or preclude informed consent or compliance with study procedures

Study Objectives This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening. Conditions: Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Hematopoietic/Lymphoid Cancer, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Relapsing Chronic Myelogenous Leukemia Intervention / Treatment: DRUG: fludarabine phosphate, DRUG: busulfan, BIOLOGICAL: anti-thymocyte globulin, DRUG: tacrolimus, DRUG: methotrexate, PROCEDURE: peripheral blood stem cell transplantation, PROCEDURE: allogeneic hematopoietic stem cell transplantation, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast phase (CP2) * Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts) * Myelodysplastic syndromes (MDS) ( all risk groups) * Other myeloproliferative disorders * DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele * DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated donors will be collected through the National Marrow Donor Program (NMDP) or other donor centers * DONOR: Age 12-75 yrs Exclusion Criteria: * Cardiac insufficiency requiring treatment or symptomatic coronary artery disease * Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal * Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted * Impaired renal function (creatinine > 2 times normal or estimated creatinine clearance < 60 ml/min) * MALE: (\[140 -age in years\] x ideal body weight \[kg\])/72 x serum creatinine (SCr) (mg/dL) * FEMALE: .85 x (\[140-age in years\] x ideal body weight \[kg\])/72 x SCr (mg/dL) * Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or acceleration of HIV replication * Female patients who are pregnant or breast feeding * Life expectancy severely limited by diseases other than malignancy * DONOR: donors who for any reason are unable to tolerate the mobilization and leukapheresis procedure * DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive * DONOR: female donors who have a positive pregnancy test

Study Objectives RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining methotrexate with vinblastine may be effective treatment for neurofibromatosis type 1 associated with progressive plexiform neurofibromas. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have neurofibromatosis type 1 associated with progressive plexiform neurofibromas. Conditions: Neurofibromatosis Type 1, Precancerous Condition Intervention / Treatment: DRUG: Methotrexate, DRUG: Vinblastine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Progressive, debilitating, severely disfiguring or life-threatening plexiform neurofibroma (PN) which is not surgically resectable and for which there is no other standard medical management. Histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings. However, if any clinical observation or scan suggests possible malignant transformation, the tumor must be biopsied prior to therapy. In addition to PN, all study subjects must have at least one other diagnostic criteria for Neurofibromatosis type 1 (NF1) listed below: * 6 or more café-au-lait spots > 0.5 cm in prepubertal subjects or > 1.5 cm in postpubertal subjects * freckling in the axilla or groin * optic glioma * 2 or more lisch nodules * a distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex) * a first degree relative with NF1 * Adequate bone marrow, renal, hepatic function: * Absolute Neutrophil Count (ANC)> 1000 and platelet count >100,000 prior to initiation of therapy * must have normal renal function: Blood Urea Nitrogen (BUN)/Creatinine <1.5x normal for age), alkaline phosphatase (ALP), albumin, total protein and bilirubin * must have normal liver function: Bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST) < 1.5x normal for age * Patients must have measurable PN by direct physical examination (documented by clinical measurement of tumor and serial photography) or by imaging studies. Most patients will have tumors that can be measured by magnetic resonance imaging (MRI), however, some patients may have cosmetically disfiguring PN which would be best measured clinically and with serial photography throughout treatment and follow-up. A measurable lesion is one whose size can be quantified in at least 2 dimensions. There must be evidence of recurrent or progressive disease as documented by an increase in size or the presence of new lesions on MRI. Progression is defined as the appearance of new tumors or a measurable increase in the sum of the product of the two longest perpendicular diameters of the index lesion(s) over a time period < 12 months prior to evaluation for this study. For purposes of this study, index PN lesions will be those PNs evaluated as the most life-threatening, debilitating, cosmetically disfiguring, and/or most easily measured. * Prior therapy: Patients with NF1 are eligible at the time of recurrence or progression of inoperable PN. A surgical consultation should be obtained prior to enrollment on the study to evaluate if tumor resection is a feasible option. Patients will only be eligible if complete tumor resection is not feasible or if a patient with a surgical option refuses surgery. Since there is no standard effective chemotherapy for patients with NF1 and progressive PN, patients may be treated on this trial without having received prior therapy. Patients must have recovered from the toxic effects of all prior therapy before entering this study. The Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 will be used for toxicity assessment. Recovery is defined as a toxicity grade < 2, unless otherwise specified in the Inclusion and Exclusion Criteria. Patients must have had their last dose of radiation therapy at least 6 weeks prior to study entry, and their last dose of chemotherapy at least four weeks prior to study entry. Patients who received granulocyte-colony stimulating factor (G-CSF) after the prior cycle of chemotherapy must be off G-CSF for at least one week prior to entering this study. * Performance status: Patients should have a life expectancy of at least 12 months and a Lansky or Karnofsky performance score of > 60. Patients who are wheelchair bound because of paralysis should be considered "ambulatory" when they are mobile and active in their wheelchairs rather than actually ambulatory. * A Pregnancy test must be negative for females of childbearing age. * Informed consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an approved document of informed consent indicating their understanding of the investigational nature and the risks of this study before beginning therapy. When appropriate pediatric patients will be included in all discussion in order to obtain verbal assent. Exclusion Criteria: * Pregnant females are excluded * Patient has had treatment with an investigational agent within the past 30 days. * Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor or immunotherapy. * Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy.

Study Objectives This is a multicenter, international, single-arm, open-label, Phase 2 trial to evaluate the efficacy and safety of avelumab in participants with metastatic Merkel cell carcinoma (MCC). Conditions: Carcinoma, Merkel Cell Intervention / Treatment: DRUG: Avelumab Location: Germany, Japan, Italy, Spain, United States, Australia, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed written informed consent * Age 18 years and above * Histologically proven MCC * Participants must have received at least 1 line of chemotherapy for metastatic MCC and must have progressed after the most recent line of chemotherapy * For Part B - Participants must not have received any prior systemic treatment for metastatic MCC. Prior chemotherapy treatment in the adjuvant setting (no clinically detectable disease; no metastatic disease) is allowable if the end of treatment occurred at least 6 months prior to study start) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST Version 1.1 (including skin lesions) * Adequate hematological, hepatic and renal function (renal function considered adequate as per protocol definition) * Highly effective contraception for both male and female participants, if the risk of conception exists * Fresh Biopsy or Archival Tumor Tissue * Estimated life expectancy of more than 12 weeks Exclusion Criteria: * Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted) * Concurrent treatment with a non permitted drug * Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co-regulatory targets such as 4-1BB * Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy \[with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions\], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent * Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the participant has not fully recovered from the surgery within 4 weeks * Concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of systemic steroids (that is, for allergic reactions or the management of immune-related adverse events \[irAE\]) while on study is allowed. Also, participants requiring hormone replacement with corticosteroids for adrenal insufficiency are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg or equivalent prednisone per day. Note: Participants receiving bisphosphonate or denosumab are eligible. * Participants with active central nervous system (CNS) metastases are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy * Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin and for Part A cervical carcinoma in situ or for Part B carcinoma in situ (skin, bladder, cervical, colorectal, breast or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer) * Prior organ transplantation, including allogeneic stem-cell transplantation * Part A: Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS) or any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. For Part B, known history of testing positive for HIV or known AIDS in consultation with the Medical Monitor or HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if anti- HCV antibody screening test positive). * Active or history of any autoimmune disease (except for participants with vitiligo) or immunodeficiencies that required treatment with systemic immunosuppressive drugs * Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to (>=) 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma) * Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v 4.0; however, sensory neuropathy Grade <= 2 is acceptable 14. Pregnancy or lactation * Known alcohol or drug abuse * Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident / stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class >= II), or serious cardiac arrhythmia requiring medication * All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the participant's tolerance of trial treatment * Any psychiatric condition that would prohibit the understanding or rendering of informed consent * Legal incapacity or limited legal capacity * Non oncology vaccine therapies for prevention of infectious disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of trial drug administration. Vaccination while on trial is also prohibited except for administration of inactivated vaccines (for example, inactivated seasonal influenza vaccine)

Study Objectives The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people. Conditions: Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Acute Myeloid Leukemia Intervention / Treatment: DRUG: vorinostat, DRUG: gemtuzumab ozogamicin, DRUG: azacitidine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Prior morphological diagnosis of acute myeloid leukemia (AML) other then acute promyelocytic leukemia (APL) according to the 2001 WHO criteria; patients with biphenotypic AML are eligible * Need for first salvage chemotherapy for persistent or relapsing disease, defined by standard criteria, after at least one course of conventional chemotherapy * A bone marrow biopsy is not required but should be obtained if the aspirate is dilute, hypocellular, or not aspirable; outside marrow exams performed within the stipulated time period are acceptable if the slides are reviewed at the study institution * Flow cytometric analysis of the marrow aspirate per institutional practice guidelines * Duration of first complete remission (CR1) < 12 months (or primary resistant disease) * Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) if relapse occurs 6-12 months post-transplant * ECOG/WHO/Zubrod performance status of 0-3 within 14 days prior to registration * Off any active therapy for AML except hydroxyurea for at least 14 days prior to study registration, with resolution of all grade 3 and 4 non-hematological toxicities * Willingness to discontinue taking any medications known to cause a risk of Torsades de Pointes * Bilirubin =< 1.5 x Institutional Upper Limit of Normal (IULN) unless elevation is due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (within 7 days prior to registration) * SGOT (AST) and SGPT (ALT) =< 1.5 x IULN unless elevation is due to hepatic infiltration by AML (within 7 days prior to registration) * Serum creatinine =< 1.5 x IULN (within 7 days prior to registration) * No clinical or radiographical evidence of heart failure * white blood cell (WBC) < 25,000/uL within 3 days prior to registration * Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/uL can be treated with leukapheresis prior to enrollment * Collection of bone marrow and peripheral blood specimens for correlative studies prior to study treatment is highly recommended; peripheral blood only is acceptable if the peripheral blast count is > 5,000/uL and > 50% of total WBC * Must agree to use adequate contraception prior to and during the study * Can understand and sign a written informed consent document; a legally authorized representative can provide consent if the patient is unable Exclusion Criteria: * Remission or second or later relapse * Diagnosis of another malignancy, unless diagnosed at least 2 years earlier and disease-free for at least 6 months after completion of curative intent therapy except: * Treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, if definitive treatment has been completed * Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or a radical prostatectomy was performed * Refractory/relapsing blast crisis of chronic myeloid leukemia (CML) * Prior anti-AML treatment with GO, histone deacetylase (HDAC) inhibitor (including the use of valproic acid for control of seizure activity or other purposes), or demethylating agent * Known hypersensitivity to GO, vorinostat, azacitidine, or mannitol * Possible central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms no leukemic blasts in the cerebralspinal fluid (CSF) * HIV-positive patients with cluster of differentiation (CD)4 count is < 200 cells/uL or if AIDS-related complications * Pregnancy; breastfeeding should be discontinued if the mother is treated with vorinostat, azacitidine, and GO * Uncontrolled systemic infection, despite appropriate antibiotics or other treatment) * Receipt of any other investigational agents

Study Objectives This is an open-label, multicenter, Phase 1/2 study of TAK-700 in combination with docetaxel and prednisone that will evaluate the safety and pharmacokinetics (PK) of the combination and will allow estimation of prostate-specific antigen (PSA) response in men with metastatic castration-resistant prostate cancer (mCRPC). Conditions: Prostate Cancer Intervention / Treatment: DRUG: TAK-700, DRUG: Docetaxel, DRUG: Prednisone Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Each patient must meet all of the following inclusion criteria: * Voluntary written consent * Male patients 18 years or older * Estimated life expectancy of 6 months or more * Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma * Radiograph-documented metastatic disease * Progressive disease * Prior surgical castration or concurrent use of an agent for medical castration * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Physical examination findings that are consistent with other study entry or exclusion criteria and identified but not excluded chronic conditions * Even if surgically sterilized, patients must Practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug, OR Abstain from heterosexual intercourse * Any use of opiates must be stable for at least 2 weeks prior to study entry * Meet screening laboratory values as specified in protocol * Suitable venous access Exclusion Criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: * Known hypersensitivity to TAK-700, docetaxel, prednisone or related compounds * Received any of the following within 30 days prior to the first dose of TAK-700: prior therapy with any investigational compound; prior herbal product known to decrease PSA; OR radiation therapy for prostate cancer * Received prior therapy with TAK-700, aminoglutethimide, ketoconazole or abiraterone (for Phase 1 only, patients previously treated with ketoconazole or abiraterone will be eligible if treatment with ketoconazole or abiraterone was discontinued at least 30 days prior to enrollment) * Received antiandrogen therapy within 4 weeks for flutamide and 6 weeks for all others prior to first dose of study drug * Received prior chemotherapy for prostate cancer * Current spinal cord compression, bilateral hydronephrosis or neck outlet obstruction * Symptoms that investigator deems related to prostate cancer * Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected * Uncontrolled cardiovascular condition * New York Heart Association Class (NYHA) Class III or IV * Uncontrolled hypertension despite medical therapy * Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C * Unwilling or unable to comply with protocol * Major surgery or serious infection within 14 days of first dose of TAK-700 * Life-threatening illness unrelated to cancer * Uncontrolled nausea, vomiting or diarrhea * Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of TAK-700

Study Objectives Part 1 (Phase Ib) Primary objective: To establish the maximum tolerated dose (MTD) of BI 836826 in combination with GemOx. Secondary objectives: To evaluate pharmacokinetics of BI 836826 when given in combination with GemOx and to investigate preliminary efficacy in terms of the overall response rate based on investigator's assessment. Part 2 (Phase II randomized) Primary objective: To investigate the efficacy by means of the overall response rate (PR+ CR) based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to R-GemOx. Secondary objective: To investigate the efficacy by means of the complete remission rate based on central review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to Rituximab + gemcitabine + oxaliplatin (RGemOx). Conditions: Lymphoma, Large B-Cell, Diffuse Intervention / Treatment: DRUG: BI 836826, DRUG: GemOx, DRUG: Rituximab, DRUG: GemOx Location: Belgium, Italy, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion criteria: * Age 18 years or older * Patients with histologically confirmed, relapsed/refractory, diffuse large B-cell lymphoma (including transformed follicular lymphoma) who have received an anti-CD20-supplemented, anthracycline-containing chemotherapy and are not eligible for high dose therapy followed by an autologous stem cell transplant, or have relapsed/progressed after autologous/allogenic stem cell transplant. Allogenic stem cell transplant performed at least 6 months prior to study entry is allowed if patients do not require immunosuppressive treatment and have no evidence of active graft-versus-host disease. * Patient has not received anti-lymphoma treatment prior to the first dose of trial medication: within past 14 days or within time that is shorter or equal to 5 half-lives of the drug if the last anti-lymphoma treatment contained an investigational agent * Screening computer tomography (CT) scan with involvement of at least 1 bi-dimensional lesion/node >1.5 cm * Screening \[18F\] fluorodeoxyglucose (FDG)- positron emission tomography (PET) scans must demonstrate positive lesion compatible with computer tomography (CT) defined anatomical tumor sites * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2 * Written signed informed consent consistent with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) and local legislation * Patients must have an acceptable organ function * Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. Non-vasectomized male patients having a female sexual partner of childbearing potential must ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least 12 months after the end of the trial. Exclusion criteria: * Eligible for curative salvage high dose therapy followed by stem cell transplant * Primary central nervous system lymphoma or known Central nervous system (CNS) involvement * Prior history of malignancy other than DLBCL except basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the uterine cervix or breast which has been treated with curative therapy. Other prior malignancies are allowed only if patient has been free of disease and without treatment other than hormones for at least past three years. * Refractory to gemcitabine and/or oxaliplatin * Contraindications for gemcitabine, oxaliplatin and/or rituximab as judged by the investigator. Hypersensitivity to oxaliplatin * Unresolved toxicity of CTCAE grade > 1from prior anti-lymphoma therapy (except alopecia) * Significant concurrent medical disease or condition which according to the investigators judgment would either compromise patient safety or interfere with the evaluation of the safety of the test drug. e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy with the exception of extra systoles of minor conduction abnormalities * An infection requiring treatment at the start of the trial medication. * Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection or HIV infection (test results done in routine diagnostics are acceptable if done within 14 days before the first study treatment dose) * Women who are pregnant, nursing, or who plan to become pregnant while in the trial.This includes the female sexual partners of a male participant * Known alcohol or drug abuse which could potentially interfere with trial participation according to investigators judgment * Prior treatment with CD37 antibody

Study Objectives The main objective of the present project is to evaluate the relevance of reticulum stress in the pathogenesis of polycystic ovary syndrome (PCOS), focusing particularly on the underlying mechanisms of insulin resistance, which is the origin of metabolic comorbidities. Furthermore, the investigators will assess the potential of insulin sensitizers as a treatment to control endoplasmic reticulum stress markers in PCOS patients. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DRUG: Metformin, DIETARY_SUPPLEMENT: Myo-inositol + folic acid Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Women diagnosed with PCOS using the Rotterdam criteria * Women of reproductive age Exclusion Criteria: * Organic, malignant, haematological, infectious or inflammatory disease * History of ischaemic heart disease (stroke or thromboembolism) * Diabetes mellitus, * Secondary causes of obesity (hypothyroidism, Cushing's syndrome) * Severe hypertension. * Smoking or alcohol habit

Study Objectives Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to poor prognosis in patients with HNSCC. EGFR targeting strategies showed clinical anti-tumor efficacy in patients with HNSCC. PF-00299804 is a second-generation quinazoline-based irreversible pan-HER inhibitor. In preclinical studies, PF-00299804 has much lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations (1.2 nM versus 2,700 nM) and produces tumor growth inhibition in gefitinib-resistant xenografts. A phase II trial of PF-00299804 in patients with recurrent or metastatic HNSCC is currently ongoing and preliminary report in ASCO 2010 showed its anti-tumor activity against HNSCC. The investigators suggest a phase II trial of pan-HER inhibitor PF-00299804 in patients with recurrent or metastatic HNSCC previously treated with platinum-based chemotherapy. Conditions: Head Neck Cancer Squamous Cell Metastatic, Head Neck Cancer Squamous Cell Recurrent Intervention / Treatment: DRUG: PF-00299804 Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed squamous cell carcinoma of head and neck * Age ≥ 18 * ECOG PS 0-2 * Documented progressive disease after platinum-based systemic chemotherapy (either cisplatin or carboplatin) with or without cetuximab * At least one bidimensionally measurable disease * Adequate organ function for treatment * Availability of tumor tissue for molecular analysis (archival or rebiopsy tissue) Exclusion Criteria: * Nasopharyngeal carcinoma * Eligibility for local therapy (surgery or radiotherapy) * Previous treatment with small molecule EGFR tyrosine kinase inhibitors * More than one systemic chemotherapy * Any major operation or irradiation within 4 weeks of baseline disease assessment * Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug * CNS metastasis with continuous corticosteroid use within 4 weeks of baseline disease assessment * Patients with known interstitial lung disease * Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months, Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension) * Concomitant malignancy (except adequately treated basal cell cancer of skin or cervical cancer in situ) * Pregnant or breast-feeding women * Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.

Study Objectives The purpose of this study is to define the optimal management of localised transitional cell carcinoma (TCC) of the urinary bladder. The main objective is to evaluate whether chemoradiation is superior to radiotherapy alone. Conditions: Transitional Cell Carcinoma of Urinary Bladder Intervention / Treatment: DRUG: Cisplatin, RADIATION: External beam radiation treatment Location: Australia, New Zealand Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically proven TCC of the urinary bladder. Mixed tumours comprising predominantly TCC and elements of squamous or adenomatous metaplasia or carcinoma are also eligible. * Clinically and radiologically localised T2, T3 or T4a non-bulky disease (<= 7cm in maximum dimension), N0, M0. If radiological evaluation of a lymph node is interpreted as "positive" this must be evaluated further by either lymph node sampling or percutaneous needle biopsy. Patients with histologically confirmed lymph node metastases will not be eligible. * Maximal TUR. N.B. Previous: * partial cystectomy; * endoscopic resection of bladder tumour/s; * intravesical chemotherapy; or * intravesical BCG does not exclude the patient from being eligible. However, the patient should have an adequate functioning bladder (this should be clarified with the referring Urologist and if need be voiding volumes should be measured). * Creatinine clearance >= 50ml/minute by calculation or measurement. * A white blood cell count >= 3.5 x 10\^9/L with an absolute neutrophil count >= 1.5 x 10\^9/L and a platelet count >= 100 x 10\^9/L. * ECOG status of 0, 1 or 2. * No age limit applies provided the patient is mentally, physically and geographically capable of undergoing treatment and follow-up. * No significant intercurrent morbidity. Exclusion Criteria: * Pure squamous carcinomas or adenocarcinomas. * Extensive or multifocal CIS change in the bladder. * T3 or T4a tumours unsuitable for curative treatment (i.e. > 7cm in any dimension), T4b, node positive and metastatic disease. * Presence of ureteric obstruction due to tumour infiltration at the UO not amenable to stenting. * Previous radiation treatment to the pelvis. * Previous significant pelvic surgery. * Significant bowel or gynaecological inflammatory disease. * Creatinine clearance < 50ml/minute by calculation or measurement. A white blood cell count < 3.5 x 10\^9/L with an absolute neutrophil count < 1.5 x 10\^9L and/or a platelet count < 100 x 10\^9/L. * Other considerations making patient unfit for Cisplatin therapy. * Prior or concurrent malignancy of any other site unless disease-free for greater than 5 years, except for: 1. non-melanoma skin cancer, and/or 2. (a) Stage T1 well differentiated prostatic carcinoma in men, and In situ carcinoma of the cervix in women. * Bladder tumour - biopsy only. These patients must be referred back for more adequate resections or else should not be included

Study Objectives This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with advanced thyroid cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by stopping blood flow to the tumor. Conditions: Recurrent Thyroid Gland Carcinoma, Stage III Differentiated Thyroid Gland Carcinoma AJCC v7, Stage III Thyroid Gland Medullary Carcinoma AJCC v7, Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7, Stage IVA Thyroid Gland Anaplastic Carcinoma AJCC v7, Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7, Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7, Stage IVB Thyroid Gland Anaplastic Carcinoma AJCC v7, Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7, Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7, Stage IVC Thyroid Gland Anaplastic Carcinoma AJCC v7, Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7, Thyroid Gland Anaplastic Carcinoma Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, DRUG: Pazopanib Hydrochloride Location: United States, Singapore, Australia, Taiwan, China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed differentiated, medullary or anaplastic thyroid cancer that is now advanced or metastatic; NOTE: patients with thyroid lymphomas or sarcomas are specifically excluded, as are patients with metastatic disease from other sites of origin to thyroid * Patients with confirmed differentiated thyroid cancer to be enrolled in the expanded/additional differentiated thyroid cancer (DTC) cohort must be thyroglobulin antibody negative * Zero, one or two prior therapeutic regimens (this includes cytotoxic plus non-cytotoxic therapeutic regimens) * Absence of sensitivity to therapeutic radioiodine (differentiated only) * Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; NOTE: disease that is measurable by physical examination only is not eligible * Life expectancy > 3 months * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 (Karnofsky >= 60%) * Leukocytes > 3,000/mcL obtained =< 7 days prior to registration * Absolute neutrophil count > 1,500/mcL obtained =< 7 days prior to registration * Platelets > 100,000/mcL obtained =< 7 days prior to registration * Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) obtained =< 7 days prior to registration (if there is reason to believe that the patient has Gilbert's syndrome, the bilirubin can be fractionated; if the fractionated bilirubin is consistent with Gilbert's syndrome and there is no other possible explanation for the elevated indirect bilirubin, the patient may be eligible for the study if and only if the direct bilirubin is =< 1.5 X institutional ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) < 2.5 X institutional ULN obtained =< 7 days prior to registration * Creatinine =< 1.5 X ULN obtained =< 7 days prior to registration * Proteinuria =< + on urinalysis (may re-check) obtained =< 7 days prior to registration * International normalized ratio (INR) =< 1.2 X the ULN obtained =< 7 days prior to registration * Blood pressure (BP) < 140 mmHg (systolic) and < 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg * Objective evidence of tumor progression in the 6 month period prior to GW786034 initiation as assessed by: * Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g. CT scan); in cases of uncertainty of tumor progression, the principal investigator of the study will be available to assist in decisions * Women of child-bearing potential must have a negative serum pregnancy test =< 7 days prior to registration; NOTE: women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; effective contraception is required for all fertile participants in the trial * Ability to understand and the willingness to sign a written informed consent document * Willingness to comply with the requirement of the study * Willingness to donate blood for correlative marker studies; (only applicable to sites within the United States) Exclusion Criteria: * Anaplastic, differentiated, medullary: a total of > 2 prior therapeutic regimens (this total includes cytotoxic plus non-cytotoxic regimens); Note: enrollment of anaplastic, differentiated, and medullary patients who have had zero, one or two prior therapeutic regimens (cytotoxic plus non-cytotoxic regimens) is allowed - provided therapy ceased > 21 days prior to registration; * NOTE: the principal investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon prior therapies * Disease that is measurable by physical examination only * Any of the following: * Radiotherapy =< 4 weeks prior to registration * Major surgery =< 4 weeks prior to registration * Radiotherapy to >= 25% of bone marrow * Concurrent therapy with octreotide unless tumor progression on this therapy has been demonstrated * Any other ongoing investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW786034 (pazopanib) or other agents used in the study * > +1 proteinuria (< 30 mg/dL) on two consecutive dipstick or other urine assessments taken at least 1 week apart; NOTE: (in cases where questions arise related to disparate proteinuria measurements, the study principal investigator \[PI\] should be consulted for assistance in determining patient study eligibility) * Corrected QT interval (QTc) prolongation (defined as a QTc interval >= 480 msecs) or other significant electrocardiogram (ECG) abnormalities (e.g. frequent ventricular ectopy, evidence of ongoing myocardial ischemia); NOTE: the principal investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon ECG changes * Receiving cytochrome P450 (CYP) interactive concomitant medications; certain medications that act through the CYP450 system are specifically prohibited in patients receiving GW786034 (pazopanib) because in vitro data indicate that the agent has the potential to interact with the cytochrome P450 isoenzymes cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) and cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); certain other agents should be used with caution * Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GSK786034 (pazopanib) * Any of the following conditions: * Serious or non-healing wound, ulcer, or bone fracture * History of abdominal fistula, gastrointestinal perforation, active diverticulitis, intra-abdominal abscess or gastrointestinal tract bleeding =< 28 days of registration * Any history of cerebrovascular accident (CVA) =< 6 months * Current use of therapeutic warfarin; Note: low molecular weight heparin and prophylactic low-dose warfarin (INR < 1.2 X ULN) are permitted; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria * History of myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks * History of venous thrombosis in last 12 weeks * Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; NOTE: a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible * History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding * Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation * Known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g. corticosteroids); NOTE: (because of the poor prognosis often associated with brain metastases and because of the potential risk of bleeding in active brain metastases associated with multi-targeted tyrosine kinase inhibitor therapy, patients with active and/or untreated brain metastases and/or those with brain metastases requiring ongoing therapy - e.g. corticosteroids - are excluded from trial enrollment; enrollment will, however, be permitted in cases of patients with longstanding treated and inactive brain metastases not requiring ongoing therapy, providing that stability of brain metastases has been demonstrated for a period of 3 months or greater as assessed by intracranial imaging - and providing that there is no indication of increased vascularity of the treated metastases by magnetic resonance imaging (MRI) imaging conducted =< 14 days prior to registration; when questions arise related to these criteria, the PI of the trial, Dr. Keith Bible, should be contacted for assistance on eligibility) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonably be expected to limit compliance with study requirements * Pregnant women; NOTE: (breastfeeding should be discontinued if the mother is treated with GW786034/pazopanib) * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy; NOTE: (appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated) * Receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of GW786034 (pazopanib); NOTE: the eligibility of patients will be determined following review of their case by the principal investigator; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications * Receiving any concomitant medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks, if possible

Study Objectives The primary objective is to explore the efficacy and safety of an all oral combination of BIBF 1120 (an inhibitor of angiogenic signalling) and metronomic cyclophosphamide in patients with multiply-relapsed advanced ovarian cancer, who have completed a minimum of two lines of previous chemotherapy and who for any reason are not suitable for further 'standard' intravenous chemotherapy treatments. Conditions: Ovarian Cancer, Fallopian Tube Cancer Intervention / Treatment: DRUG: BIBF 1120 Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Female subjects, ≥18 years, histologically proven recurrent advanced epithelial ovarian, fallopian tube or primary peritoneal carcinomas * Have either undergone a hysterectomy or bilateral oophorectomy/salpingectomy and/or have been postmenopausal for 24 consecutive months (i.e. who have not had menses at any time in the preceding 24 consecutive months without an alternative medical cause) * Performance status 0-2 * Adequate organ function * Life expectancy >6 weeks * Has received 2 or more lines of chemotherapy for ovarian cancer and patient is platinum resistant or platinum intolerant or not suitable for any further standard intravenous chemotherapy * No previous oral cyclophosphamide, nintedanib, or other tyrosine kinase inhibitors such as cediranib but patients can have received anti-VEGF therapies such as bevacizumab as they will be stratified for this * Measurable lesions according to RECIST 1.1 criteria or serum CA125 levels for evaluation by GCIG CA125 criteria are welcomed but not a prerequisite for inclusion as response will only be assessed for those with evaluable disease * Able to give written informed consent and to complete QoL Exclusion Criteria * Carcinosarcoma or malignant tumour of non-epithelial origin (e.g. germ cell tumour, sex cord-stromal tumour) of the ovary, fallopian tube or peritoneum * Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture * Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other GI disorders or abnormalities that would interfere with drug absorption or inability to take oral medication * Active brain metastases (i.e. symptoms deteriorating, changing condition in < 4 weeks) or leptomeningeal disease. Trial entry is allowed if the brain metastases are stable (asymptomatic or condition stable for > 4 weeks). * Dexamethasone for brain metastases is allowed if administered as stable dose for > 4 weeks before randomisation (if < 4 weeks then the patient is not eligible) * Clinically relevant therapy-related toxicity from previous chemotherapy and radiotherapy * History of major thromboembolic event within the last 6 months, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation (>3 months if on warfarin, PT / INR needs to be monitored regularly as per table 8.1 in protocol) * Known inherited or acquired bleeding disorder * Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within the past 6 months, congestive heart failure > NYHA II, severe peripheral vascular disease, significantly relevant pericardial effusion * History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months * Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vessels * Laboratory values indicating an increased risk for adverse events: 1. calculated GFR < 45 ml/min. Sites can use any calculation method according to local practice. 2. absolute neutrophil count (ANC) < 1.5x109/L 3. platelets < 100 x109/L 4. haemoglobin < 90 g/L 5. proteinuria CTCAE 2 or greater 6. total bilirubin > x 2 ULN 7. ALT and/or AST > 1.5 x ULN 8. unless liver metastases present when ALT or AST > 2.5 ULN 9. International normalized ratio (INR) > 2 or activated partial thromboplastin time (APTT) >1.5 x ULN in the absence of therapeutic anticoagulation. INR > 4 or APTT > 2.5 x ULN in presence of therapeutic anticoagulation * Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal or antiviral therapy), including hepatitis B and/or C infection, HIV- infection * Poorly controlled diabetes mellitus or patient on sulphonylurea-type hypoglycaemics (e.g. gliclazide) as main diabetic control (as contraindicated with cyclophosphamide) * Previous breast cancer patients are permitted only if diagnosis and any chemotherapy treatment for this was > 5 years previously and there is no evidence of metastatic breast cancer at trial entry (Please contact UCL CTC / CI if patient still on hormone treatment for breast cancer). * Other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included: 1. non-melanoma skin cancer (if adequately treated) 2. cervical carcinoma in situ (if adequately treated) 3. prior or synchronous endometrial cancer (if adequately treated), provided all of the following criteria are met: G1 or G2, no LVSI and FIGO (2010) stage IA only * Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease or a laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study * Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule e.g. active alcohol or drug abuse * Any contraindications for therapy with cyclophosphamide, e.g. a history of severe hypersensitivity reactions to listed excipients for cyclophosphamide treatment with other investigational drugs * Patients should not commence trial treatment within 6 weeks of any major surgical procedure * Participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial * Chemotherapy, including immunotherapy or monoclonal antibody treatment (VEGF) within 4 weeks of starting study treatment * Hormone treatment for ovarian cancer within 2 weeks of starting study treatment (ongoing HRT is allowable) * Any previous tyrosine kinase inhibitor treatment that has predominantly anti-angiogenic action * Radiotherapy within 3 months not allowed except when given for symptom control >28d previously. All patients receiving any radiotherapy will require evidence of recurrent ovarian cancer outside the irradiated field either on imaging or via rising CA125 * Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients of nintedanib

Study Objectives The purpose of this study is to test the safety of a new plan for treating glioblastoma. The usual first treatment for glioblastoma is to give focused radiation over 6 weeks in combination with a chemotherapy called temozolomide. In this study the radiation will be given over 2 weeks in combination with temozolomide and another drug, bevacizumab, will also be given. Our idea is that this treatment plan may attack both the tumor and the blood vessels feeding the tumor more effectively. This study will look at what effects, good or bad, this approach has on the patient and the tumor. Conditions: Brain Cancer, Malignant Glioma Intervention / Treatment: OTHER: radiotherapy (RT) in combination with temozolomide and bevacizumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Pathologic diagnosis of glioblastoma or grade IV glioma. * Tumor volume should be less than 60 cc (approximately 5cm maximum diameter). * Age > or = to 18 * KPS ≥70 * Granulocyte count >1.5 X 10 9/L * Platelet count >99 X 10 9/L * SGOT < 2.5X upper limit of normal (ULN) * Serum creatinine < 2X ULN * Bilirubin < 2X ULN * All patients must sign written informed consent Exclusion Criteria: * Any prior chemotherapy, radiotherapy and biologic therapy for glioma. * Any prior experimental therapy for glioma. * Multicentric glioma * Other concurrent active malignancy (with the exception of cervical carcinoma in situ or basal cell ca of the skin). * Serious medical or psychiatric illness that would in the opinion of the investigator interfere with the prescribed treatment. * Pregnant or breast feeding women. * Refusal to use effective contraception * Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg) * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 12 months prior to Day 1 * History of stroke or transient ischemic attack * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 * History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening * Known hypersensitivity to any component of bevacizumab

Study Objectives The aim of the study is to assess the clinical utility of 18F-fluoro-deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) and Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in castration-resistant prostate cancer patients. The study will assess how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment with Enzalutamide in castration-resistant prostate cancer patients. In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement. Conditions: Prostate Cancer Metastatic Intervention / Treatment: DRUG: Enzalutamide, DEVICE: 18-FDG PET/CT, DEVICE: Whole body MRI, DEVICE: Bone scan Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male aged 18 years or older; * Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features; * Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy; * Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 5 ng/mL but preferably >10 ng/mL; * Progressive disease as defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 18F-FDG PET/CT, Whole Body MRI or both; * Castrate serum levels of testosterone < 50 ng/dL or < 1.7 nmol/L; * Anti-androgen withdrawal for at least 6 weeks for bicalutamide, nilutamide or flutamide for at least 6 weeks; * No prior treatment with cytotoxic chemotherapy; * Eastern Cooperative Oncology Group (ECOG) score 0-2; * A life expectancy of at least 12 months; * Written informed consent. Exclusion Criteria: * Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment; * Known or suspected brain metastasis or active leptomeningeal disease; * History of another malignancy within the previous 5 years other than curatively treated non melanomatous skin cancer; * Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit; * Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit; * Hemoglobin <6 mmol/L, White blood cells < 4.0 x10\^9/L, platelets < 100 x 10\^9/L; * History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrolment (Day 1 visit); * Contra-indication for MRI (e.g. pacemaker).

Study Objectives A randomized, double-blind, placebo-controlled intervention trial involving 100 treated subjects undergoing endonasal trans-sphenoidal (ENTS) resection of pituitary lesion. Subjects will be randomized into two groups: 50 treated in the opioid-sparing arm and 50 treated in the standard post-operative medication arm. Conditions: Pituitary Tumor, Pain Intervention / Treatment: DRUG: IV Caldolor, DRUG: IV Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Adult patient undergoing ENTS surgery for resection of pituitary tumor. * Adults >18 years and <80 years of age. * English speaking and literate or able to understand the use of a pain scale. * Body Mass Index >19 and <40 kg/m2 Exclusion Criteria: * Renal failure (acute or chronic) or creatinine >2.0 * Allergy or intolerance to acetaminophen, ibuprofen, or opioids * Pre-operative opioid tolerance, dependence, or abuse * Anaphylaxis to opioids * History of peptic ulcer disease or recent gastrointestinal bleed requiring surgery * Cirrhosis, hepatitis, liver transplant, or liver function studies out of normal range, defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin> 3x upper limit of normal range * Subject unwilling or unable to sign informed consent for the study * Pregnancy * Incarcerated patients

Study Objectives This is a prospective double-blind, randomized, parallel-group, placebo-controlled trial designed to examine the effect of supplementation with 50,000 IU vitamin D3 for 3 months on Polycystic Ovary Syndrome (PCOS) prognosis, serum 25-Hydroxy Vitamin D (25(OH)D) level, serum chromium level, insulin resistance, and Body Mass Index (BMI), in 60 overweight Jordanian female patients diagnosed with PCOS and with hypovitaminosis D. Conditions: Polycystic Ovary Syndrome, Hypovitaminosis D Intervention / Treatment: DRUG: 50,000 IU vitamin D3, DRUG: Placebo Location: Jordan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Female gender. * Aged between 18 and 49 years old. * Ethnic group (Caucasian, Middle-eastern). * Overweight (BMI 25-30 kg\^m2). * Diagnosed with Polycystic ovary syndrome according to Rotterdam criteria (Rotterdam SHRE-ASRM Sponsored Polycystic ovary syndrome consensus workshop group, 2004). * Diagnosed with hypovitaminosis D (serum 25(OH)D level < 20 ng/mL). * Inadequate dietary intake of vitamin D (<600 IU/day or <15μg/day). * Physical examination being assessed and accepted by the attending physician. * Systolic blood pressure within the normal range (90-140 mmHg). * Diastolic blood pressure within the normal range (60-90 mmHg). * Heart rate within the normal range (60-100 BPM). * Oral body temperature within the normal range (35.9 - 37.6 Cᵒ). * Normal complete blood count , Liver Function enzymes test , Aspartate Transaminase (AST) , Alanine Transaminase (ALT) and Kidney function tests , Blood Urea Nitrogen (BUN) and Serum Creatinine (SrCr). * Participant is willing and able to give informed consent for participation in the study. * Able and willing to comply with all study requirements. Exclusion Criteria: * Female participants who are pregnant, lactating or planning pregnancy during the course of the study. * Ethnic group: non Caucasian. * Females aged <18 or >49 years old. * Underweight, normal body weight ,Body Mass Index (BMI) < 25 kg\^m2 * Obese or morbidly obese (BMI > 30 kg/m2) * Diagnosis with type 1 or type 2 diabetes mellitus, hypothyroidism, hyperthyroidism, liver disease, renal dysfunction, cardiovascular diseases, androgen-secreting tumor, Cushing syndrome, congenital adrenal hyperplasia, hyperprolactinemia, and/or virilism. * Known history or presence of food allergies or intolerance (e.g dairy products or gluten-containing foods), or any known condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs. * History of drug or alcohol abuse, smoking of 10 cigarettes or more (or equivalent) per day. * Participants who took medications known to affect metabolic parameters, such as metformin and corticosteroid drugs, vitamin D and calcium. * Adequate dietary intake of vitamin D (600 IU/day or 15μg/day or more). * Participation in another clinical or bioequivalence study within 90 days prior to the start of this study period. * Participants with abnormal Electrocardiogram (ECG). * Participants with any abnormal laboratory results excluding \[ 25(OH)D, Creatinine (Cr), Calcium (Ca), phosphorus (PO4), C-reactive protein(CRP) , triglyceride , High Density Lipoprotien Cholesterol (HDL-C), Low Density Lipoprotien Cholesterol (LDL-C), total cholesterol (TC)/HDL-C ratio, fasting insulin , fasting blood glucose, oral glucose tolerance test, impaired glucose tolerance, Progesterone, total testosterone, sex hormone binding globulin, parathyroid hormone and free androgen index\].

Study Objectives To determined what dose of topotecan can be safely given with daily pazopanib. Conditions: Solid Tumours Intervention / Treatment: DRUG: topotecan, DRUG: pazopanib Location: United States, Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: SCREENING Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria - * signed, written informed consent. * at least 18 years of age. * ECOG performance status 0 or 1. * Subjects must have histologically or cytologically confirmed diagnosis of advanced cancer and a solid tumor malignancy that has relapsed or is refractory to standard therapy or for which there is no established therapy. * able to swallow and retain oral medications. * females are eligible to enter and participate in this study providing adequate established contraception is being practiced. Exclusion Criteria * had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) * received an investigational drug within 30 days or 5 half-lives (whichever is longer). * received prior treatment with pazopanib/investigational anti-angiogenic compounds. * presence of uncontrolled infection. * pregnant or lactating. * poorly controlled hypertension (SBP of ? 140 mmHg, or DBP of ? 90 mmHg. * Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.- * arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months. * any unresolved bowel obstruction or diarrhea ? Grade 1. * received an allogeneic bone marrow transplant. * known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan. * any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study. * psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. * clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.

Study Objectives The purposes of this study are: 1. To determine the efficacy of inter pleural analgesia 2. To determine the plasmatic concentration of ropivacaine by inter pleural road Conditions: Postoperative Pain, Cancer Intervention / Treatment: DRUG: Ropivacaine Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Thoracotomy for oncology thoracic surgery * Secondary or primary cancer * American Society of Anesthesiology (ASA) class 1 or 2 Exclusion Criteria: * Ropivacaine hypersensibility * Psychiatric disorders * Incapacity of using visual analog scale

Study Objectives This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib and combination chemotherapy works in treating patients with newly diagnosed stage II-IV anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether brentuximab vedotin and combination chemotherapy is more effective than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma. Conditions: Anaplastic Large Cell Lymphoma, ALK-Positive, Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma, Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma, Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma Intervention / Treatment: DRUG: Brentuximab Vedotin, DRUG: Crizotinib, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, DRUG: Etoposide, DRUG: Ifosfamide, DRUG: Methotrexate Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Newly diagnosed patients with histologically proven ALCL (International Classification of Diseases for Oncology \[ICD-0\] code: 9714/3) * Disease must be cluster of differentiation (CD)30 positive * Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local institutional standards) * Patients must have stage II, III, or IV disease * Patients must have a life expectancy of >= 8 weeks * Adequate Liver Function Defined As: * Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) * Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) < 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is 45 U/L (within 7 days prior to enrollment) * If the lab abnormality is thought to be due to the lymphoma the patient is eligible and dose adjustments should be made * Adequate Cardiac Function Defined As: * Shortening fraction of >= 27% by echocardiogram, or * Ejection fraction of >= 50% by radionuclide angiogram * Adequate Pulmonary Function Defined As: * Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air unless current dysfunction is due to the lymphoma in which case the patient is eligible Exclusion Criteria: * Patients with central nervous system (CNS) disease are not eligible * Patients with disease limited to the skin are not eligible, regardless of how wide-spread * Patients with stage I disease are not eligible * Patients who have received any prior cytotoxic chemotherapy for the current diagnosis of ALCL or any cancer diagnosed previously are not eligible * Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass; emergent steroid treatment and/or radiation treatment should stop once protocol therapy is initiated * Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL * Female patients who are pregnant are not eligible; pregnancy tests must be obtained in girls who are post menarchal * Lactating females are not eligible unless they have agreed not to breastfeed their infants * Sexually active patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of treatment and for 3 months after stopping treatment * Patients with Down syndrome are not eligible due to the amount of methotrexate and potential for side effects * Patients with an immunodeficiency that existed prior to diagnosis such as primary immunodeficiency syndromes or organ transplant recipients are not eligible * Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow therapeutic indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed * CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed * CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St. John's wort are not eligible; the topical use of these medications (if applicable) is allowed * Patients that are known to be positive for human immunodeficiency virus (HIV) are not eligible; note: inclusion of HIV positive patients will be considered at a later date * Patients who weigh < 10 kg are not eligible

Study Objectives The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy. Conditions: Lung Cancer Intervention / Treatment: PROCEDURE: T790M+ Testing, PROCEDURE: Baseline Visit Blood & Urine Testing, PROCEDURE: Baseline ECG, PROCEDURE: Visual Slit-Lamp Testing, DRUG: AZD9291 Dosing Location: Canada, Korea, Republic of, Italy, Brazil, Spain, United Kingdom, Denmark, Australia, Belgium, Ireland, Saudi Arabia, Austria, Taiwan, China, Argentina, Sweden Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures * Adults (according to each country regulations for age of majority) * Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation * Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment * World Health Organization (WHO) performance status 0-2 * Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline (please refer to IB for guidance) * ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6 * Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential * Male patients must be willing to use barrier contraception, i.e., condoms Exclusion Criteria: * Previous (within 6 months) or current treatment with AZD9291 * Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 * Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance. * Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration; * Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD * Any of the following cardiac criteria: 1. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula : 2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block) 3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events * Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment * History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291

Study Objectives This is a Phase II, open label, single arm, multi-centre study investigating the safety and efficacy of ofatumumab plus bendamustine in subjects with untreated or relapsed CLL. Each subject from the screening phase who is willing to participate in the study and is found eligible according to the inclusion and exclusion criteria will enter the treatment phase and will receive a maximum of 6 Cycles of study treatment (ofatumumab plus bendamustine). All subjects will receive 3 Cycles of study treatment (Cycles 1, 2 and 3). Eligibility to receive study treatment for Cycles 4, 5 and 6 will be assessed following the 3rd Cycle. Subjects who have achieved at least stable disease with acceptable toxicity following 3 Cycles of treatment will be eligible to continue to receive study treatments for a maximum of 3 further Cycles. In case of progressive disease, at, or at any time after the start of Cycle 4, subjects must discontinue further study treatment and move into the study's follow-up period. During the treatment phase, all eligible subjects will be allocated to receive the following study treatments: 1. Subjects with Untreated CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days) in combination with up to 6 Cycles of intravenously infused bendamustine (90 mg/m2, Days 1 and 2, every 28 Days). 2. Subjects with Relapsed CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days) in combination with up to 6 Cycles of intravenously infused bendamustine (70 mg/m2, Days 1 and 2, every 28 Days). The studies primary endpoint is overall response rate (ORR) as determined by Investigator evaluation. The ORR is the percentage of subjects achieving an objective response (i.e., partial response or better), using the IWCLL updated NCI-WG guidelines. Response assessments are planned at the following time-points: After 3 Cycles of ofatumumab plus bendamustine treatment, after 6 Cycles of ofatumumab plus bendamustine treatment and after the last dose, if not after 6 cycles, of ofatumumab plus bendamustine treatment. Follow-up assessments will be performed every 3 months following the last study treatment. The follow-up period will last for a maximum of 3 years. Response evaluation assessments to determine subject response or progression will be performed during the follow-up period, according to the IWCLL updated NCI-WG guidelines. Following progression, only survival status and details concerning the subject's next CLL therapy will be recorded. Conditions: Chronic Lymphocytic Leukemia (CLL), Leukaemia, Lymphocytic, Chronic Intervention / Treatment: BIOLOGICAL: Ofatumumab, DRUG: Bendamustine Location: Czech Republic, Italy, Spain, United States, Greece, Belgium, Russian Federation, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * A diagnosis of CLL defined by a circulating B-lymphocyte count of greater than or equal to 5,000/uL at study entry or at any time in the past and flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to first dose of study treatment. * Active disease and indication for treatment based on the IWCLL updated NCI-WG guidelines, defined by presence of at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development or worsening of anaemia and/or thrombocytopenia; Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly; Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy; Progressive lymphocytosis with an increase of more than 50% over a two-month period or a lymphocyte doubling time of less than 6 months. * A minimum of any one of the following disease-related symptoms must be present: a. Unintentional weight loss greater than or equal to 10% within the previous six months; b. Fevers greater than 100.5°F (38.0°C) for greater than or equal to 2 Weeks without evidence of infection; Or c. Night sweats for more than 1 month without evidence of infection. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. * Age greater than or equal to 18 years. * Signed written informed consent from either the subject, or their legally acceptable representative if the subject is incapable of giving their own consent, prior to performing any study-specific tests or procedures. * Subjects enrolled into the previously untreated subject cohort must also meet all of the following criteria: No prior treatment for CLL (prior corticosteroid immunosuppression treatment for autoimmune hemolytic anaemia and idiopathic thrombocytopenic purpura (ITP) is permitted); Be considered inappropriate for fludarabine-based therapy for reasons that include, but are not limited to, advanced age or presence of co-morbidities. * Subjects enrolled into the relapsed subject cohort must also meet the following criteria: Relapsed CLL: defined as a subject who has received at least one prior CLL therapy and previously achieved a complete or partial remission/response lasting at least 6 months. Exclusion Criteria: * Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of the last anti-CLL therapy. * Previous autologous or allogeneic stem cell transplantation. * Active autoimmune hemolytic anaemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) requiring corticosteroid therapy greater than 25 mg prednisone (or equivalent) or chemotherapy. * Known transformation of CLL (e.g. Richter's). * Known central nervous system involvement by CLL. Screening laboratory values: Platelets less than 100 x 109/L (unless due to CLL involvement of the bone marrow). Neutrophils less than 1.5 x 109/L (unless due to CLL involvement of the bone marrow). Serum creatinine greater than 1.5 times the upper limit of normal (ULN); subjects with a serum creatinine greater than 1.5 x ULN will be eligible if the calculated creatinine clearance \[Cockcroft, 1976\] is greater than or equal to 30 mL/min. Total bilirubin greater than 1.5 times ULN (unless due to liver involvement by CLL or Gilbert's disease). Transaminases greater than 2.5 times ULN. * Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known Human Immunodeficiency Virus (HIV) disease. All HIV-positive subjects are excluded from this study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy. * Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumour was successfully treated with curative intent at least 2 years prior to trial entry.\* * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to first study treatment, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.\* * History of significant cerebrovascular disease or event with significant symptoms or sequelae.\* * Glucocorticoid use, unless given in doses less than or equal to 25mg/Day prednisone (or equivalent) for less than 7 Days for exacerbations other than CLL (e.g. asthma).\* * Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but Hepatitis B core antibody (HBcAb) positive, a Hepatitis B Virus (HBV) DNA test will be performed and if positive the subject will be excluded. * Known or suspected hypersensitivity to ofatumumab or bendamustine that in the opinion of the investigator is a contraindication to their participation in the present study. * Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 Weeks prior to first study treatment dose, whichever is longer, or participation in any other interventional clinical study. * Known or suspected inability to comply with the study protocol. * Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last ofatumumab dose. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilisation if male partner is sole partner for that subject. For females in the USA, the use of a double barrier method is also considered adequate (condom or occlusive cap plus spermicidal agent). * Subjects can participate in the study if in the opinion of the investigator it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data.

Study Objectives The purpose of this study is to evaluate the 1-year treatment failure rate of two sequential chemotherapy regimens: weekly docetaxel plus cisplatin followed by gemcitabine; and gemcitabine plus cisplatin followed by weekly docetaxel。 Conditions: Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Docetaxel, Cisplatin, DRUG: Gemcitabine, Cisplatin Location: Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologic or cytologic diagnosis of stage IIIB/IV NSCLC, no prior chemotherapy * Age > 18 years and < 75 years * WHO PS: 0,1 * Unidimensional or bi-dimensional measurable disease * Neutrophils > 1.5 109/l, Platelets > 100 109/l, Hemoglobin > 10g/dl, Total bilirubin < 1.5 UNL, AST (SGOT) and ALT (SGPT) < 2.5 UNL, Alkaline phosphatases < 5 UNL; except in presence of only bone metastasis and in the absence of any liver disorders * Creatinine < 1 UNL, and creatinine clearance should be > 60 ml/min. * Life expectancy > 12 weeks Exclusion Criteria: * Pregnant, or lactating patients * Known clinical brain or leptomeningeal involvement * Pre-existing motor or sensory neurotoxicity of a severity > grade 1 by NCIC-CTG criteria * CHF, angina or arrhythmias * History of significant neurological or psychiatric disorders * Active uncontrolled infection * Contraindication for the use of corticosteroids * Concurrent treatment with other experimental drugs within 30 days prior to study entry * Concurrent treatment with any other anti-cancer therapy

Study Objectives This protocol investigates the effect of a high dose dexamethasone regimen in the treatment of postoperative pain following Transoral Robotic Surgery (TORS). The protocol consists of three substudies. 1. Randomized double-blinded clinical trial assigning half of the participants to a high-dose dexamethasone regimen while the other half will receive a low-dose dexamethasone dosage and placebo in the first postoperative period. 2. A investigation of "Why in hospital?" following TORS. From the first postoperative day until discharge reasons for continued hospitalization will be registered in order to identify clinical and organizational factors contributing to hospitalization 3. An assessment of "Days Alive and Out of Hospital" following TORS. From the day of surgery and the first 12 postoperative months all admissions to a hospital ward will be registered along with admission reasons. Any death during the first 12 months will be noted with a cause of death. Conditions: Analgesia, Surgery, Cancer of Head and Neck, Oropharyngeal Cancer, Carcinoma of Unknown Primary, Pain, Postoperative, Postoperative Pain Intervention / Treatment: DRUG: Dexamethasone, DRUG: Placebo Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * 18 years or older * Ability to provide a written informed consent * ECOG/WHO performance status 0-2 * Squamous cell carcinoma of unknown primary or obstructive sleep apnea * Booked for TORS based on radiologic and clinical assessment by an ENT surgeon oTORS for obstructive sleep apnea must be preceded by a Drug-induced sleep endoscopy (DISE) examination * Negative Urine HCG pregnancy test for women in the fertile age. Exclusion Criteria: * Serious medical comorbidities (ECOG/WHO performance status >2). Other contraindications to surgery * Distant metastasis * Active Herpes zoster * Previous head and neck cancer * Significant trismus, maximum inter-incisal opening 35mm * Insulin dependent diabetes * Allergy to glucocorticoids * Preoperative daily use of systemic glucocorticoids <90 days before the surgery Glucocorticoids administered to the patient's routine examination under general anesthesia with bilateral biopsies from base of the tongue, adenoidectomy and concurrent tonsillectomy are not a part of this exclusion criteria. Only systemic daily use <90 prior TORS is an exclusion criterion. * Preoperative use of biological anti-inflammatory medication <90 days before the surgery * Active gastric ulcer in the opinion of the investigator * Pregnancy/Breastfeeding

Study Objectives The purpose of this study is to evaluate the efficacy and toxicity of Rituximab combined with ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) in the patients with diffuse large B cell lymphoma (DLBCL). Conditions: Lymphoma Intervention / Treatment: DRUG: Rituximab combined with ESHAP Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age range 18-70 years old * Histological confirmed diffuse large B cell lymphoma * ECOG performance status no more than 2 * Life expectancy of more than 3 months * Relapse or refractory after the first-line chemotherapy of DLBCL * No evidence of bone marrow involvement * Normal laboratory values: hemoglobin > 8.0g/dl, neutrophil > 1.5×109/L, platelet > 80×109/L, serum creatine < 1× upper limitation of normal(ULN), serum bilirubin < 1× ULN, ALT and AST < 1.5× ULN Exclusion Criteria: * Pregnant or lactating women * Serious uncontrolled diseases and intercurrent infection * The evidence of CNS metastasis and bone marrow involvement * History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix * History of allergic reaction/hypersensitivity to rituximab

Study Objectives BBR 2778 is a novel aza-anthracenedione that has activity in experimental tumors and shows reduced potential for cardiotoxicity in animal models. This cytotoxic agent has structural similarities with mitoxantrone as well as general similarities with anthracyclines (such as the tricyclic central quinoid chromophore). Conditions: Lymphoma, Non-Hodgkin Intervention / Treatment: DRUG: pixantrone, cyclophosphamide, vincristine, rituximab, prednisone, DRUG: Vinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab Location: Hungary, Uruguay, United States, France, Poland, India, Italy, Peru, Ecuador, Ukraine, United Kingdom, Russian Federation, Bulgaria, Estonia, Mexico, Germany, Costa Rica, Romania, Argentina, Panama Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically confirmed aggressive \[de novo or transformed\] NHL according to REAL/WHO classification. * At least one objectively measurable lesion as demonstrated by CT, spiral CT, or MRI and plain radiograph of the chest (chest x-ray, for chest lesions only) that can be followed for response as target lesion. * Relapse after 2 or more prior regimens of chemotherapy * ECOG performance status of 0, 1, or 2 * Adequate hematologic, renal and hepatic function * LVEF ≥50% determined by MUGA scan Exclusion Criteria: * Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450 mg/m² * Prior allogenic stem cell transplant * Histological diagnosis of Burkitt lymphoma, lymphoblastic lymphoma or Mantle cell lymphoma * Active CNS lymphoma or HIV-related lymphoma. * Any chemotherapy, radiotherapy, or other anticancer treatment (including corticosteroid, 10 or more mg/day of prednisone or equivalent) within the 2 weeks before randomization * Pregnant women or nursing mothers

Study Objectives This is a prospective, single-center randomized trial with three arms, and an allocation ratio of 1:1:1. The study design is an efficacy study to evaluate the effect of metformin and coach-directed behavioral weight loss versus self-directed weight loss on insulin-like growth factor (IGF)-1 and IGF-1 to THE IGFBP-III ratio blood levels after 6 and 12 months of intervention. The coach-directed Behavioral Weight Loss arm is a web-based remote delivery and communication system that promotes healthy behavioral changes. The Metformin arm is a pharmaceutical intervention of oral metformin. This is a secondary prevention study for men and women who have survived solid malignant tumors Conditions: Breast Cancer, Prostate Cancer, Lung Cancer, Colon Cancer, Melanoma of Skin, Endometrial Cancer, Liver Cancer, Pancreatic Cancer, Rectal Cancer, Kidney Cancer, Other Solid Malignant Tumors Intervention / Treatment: DRUG: Metformin, BEHAVIORAL: Coach Directed Behavioral Weight Loss, BEHAVIORAL: Self-control weight loss Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Women and men ages 18 or older * Have been previously diagnosed with a malignant solid tumor, completed their required surgical, and/or chemotherapy and/or radiation curative intent therapy at least three months prior to enrollment, and have an anticipated treatment-free life span of 12 months or longer. Chemoprophylaxis with tamoxifen or aromatase inhibitors for breast cancer in women and anti- Luteinizing hormone-releasing hormone (LHRH) therapy for prostate cancer in men will be permitted. * Have a BMI of 25 kg/m\^2 or greater and weight <=400 lbs. * Willingness to accept randomization to each of the three arms * Willingness to change diet, physical activity, and weight * Regular access to computer with a reliable Internet connection * Ability to send and receive emails * Ability to complete online forms * Access to phone * Willingness to provide written informed consent Exclusion Criteria: * Women who are breastfeeding, pregnant, or planning pregnancy within the next year * Medication-treated diabetes * Fasting blood glucose >=200 mg/dL, or fasting blood glucose >=126 and <200 mg/dL and HbA1C >=7% * Current or prior regular use of metformin within the past 3 months * Uncontrolled concurrent medical condition likely to limit compliance with the study interventions * Received any chemotherapy (unless anti-hormonal therapy) and/or radiation three months or less prior to the proposed intervention date * Have a prior history of lactic acidosis by self-report * Prior or planned bariatric surgery * Have significant renal disease or dysfunction defined as Estimated glomerular filtration rate (eGFR)<45 * Have significant hepatic dysfunction \[Aspartate aminotransferase (AST)/Alanine transaminase (ALT) ≥ 2 x upper limit of normal (ULN) or reported liver disease\] * Self-reported average consumption of > 14 alcoholic drink per week * Currently enrolled or planned to enroll in weight loss program * Hemoglobin <9 g/dl * Platelet count <100 * White blood cell count (WBC) <2.5 * Plans to relocate from the area within one years * Use of prescription weight loss medication(s) (e.g., lorcaserin, topiramate/phentermine, phentermine, liraglutide, and bupropion/naltrexone), including off label use of drugs for weight loss or over-the-counter weigh loss medications such as Orlistat within the past 6 months.

Study Objectives The purpose of this study is to compare the 1-year adherence to upfront adjuvant AI for postmenopausal, early stage breast cancer in the two observational arms; Standard Treatment and Standard Treatment plus PSP arm after one year Conditions: Breast Cancer Location: China Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Provide signed and dated written Informed Consent * Have been taking upfront AI adjuvant therapy in line with current SmPC * Be capable of completing drug intake by herself * Be capable of understanding Chinese Exclusion Criteria: * Upfront adjuvant hormonal therapy by an AI to which upfront adjuvant indication has not been granted by SFDA * Upfront adjuvant AI medication which has exceeded over eight weeks * Previous adjuvant hormonal therapy for breast cancer lasting over 8 weeks other than AI * Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)

Study Objectives To assess and compare the pharmacokinetics of Melphalan HCL for Injection (Propylene Glycol-Free) versus Alkeran for Injection in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT). Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection, DRUG: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Patients with symptomatic MM requiring treatment at diagnosis or anytime thereafter. * Patients with MM who qualify for ASCT therapy who have received appropriate primary induction therapy for transplantation. * Adult patients (≥ 18 years old) who are 70 years of age or younger at time of transplant; patients greater than 70 years of age may qualify on a case-by-case basis if the patient meets local institutional criteria to receive a total melphalan dose of 200 mg/m2 as a conditioning regimen and if approved by the Medical Monitor. * Patients with an adequate autologous graft which is defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based upon patient weight. * Patients with adequate organ function as measured by: * Cardiac: Left ventricular ejection fraction at rest >40% (documented within 12 weeks prior to Day -3). * Hepatic: Bilirubin <2 × the upper limit of normal (ULN) and ALT/AST <3 × ULN. * Renal: Creatinine clearance >40 mL/minutes (measured or calculated/estimated). * Pulmonary: DLCO, FEV1, FVC >50% of predicted value (corrected for Hgb) or O2 saturation > 92% on room air (documented within 12 weeks prior to Day -3) Exclusion Criteria: * Patients who have never advanced beyond Stage 1 MM since diagnosis. * Patients who have previously received more than one autologous stem cell transplant. * Patients with plasma cell leukemia. * Patients with MM and systemic AL amyloidosis. * ECOG performance status ≥2. * Patients with uncontrolled hypertension. * Patients with an active bacterial, viral, or fungal infection. * Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent >5 years previously will be allowed. Cancer treated with curative intent <5 years previously will not be allowed unless approved by the medical monitor. * Female patients who are pregnant (positive ß-HCG) or breastfeeding. * Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 1 month following study treatment with Melphalan HCl for Injection (Propylene Glycol-Free). * Patients seropositive for HIV. * Patients who are unwilling to provide informed consent. * Patients receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 21 days prior to the ASCT, or planning to receive any of these treatments prior to study discharge. * Patients concurrently participating in any other clinical study. * Patients who are hypersensitive or intolerant to any component of the study drug formulation.

Study Objectives The goal of this clinical research study is to find the highest tolerable dose of vemurafenib that can be given in combination with either everolimus or temsirolimus. The safety of these drug combinations will also be studied. Vemurafenib is designed to block BRAF inside the cancer cells, which is a mutation that is involved in cancer cell growth. Temsirolimus and everolimus are designed to block the growth of cancer cells, which may cause cancer cells to die. Conditions: Advanced Cancer, Solid Tumor Intervention / Treatment: DRUG: Vemurafenib, DRUG: Everolimus, DRUG: Temsirolimus Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Confirmation of BRAF mutation-positive malignancy is required for selection of patients for vemurafenib therapy * Measurable or non-measurable disease by RECIST 1.1. * Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy available that improves survival by at least three months. * Patients must be at least 3 weeks past receiving cytotoxic therapy and at least 5 half-lives after their previous treatment or 3 weeks, whichever is shorter, after biologic therapy. Patients may receive palliative radiotherapy immediately or during treatment provided that not all target lesions are radiated. * ECOG performance status <= 2 (Karnofsky >= 60%; Lansky Score >= 50). * Patients must have normal organ and marrow function defined as: absolute neutrophil count >=1,000/mL; platelets >=50,000/mL; creatinine < 2.0; total bilirubin < 2.0; ALT(SGPT) <= 3 X ULN; Exception for patients with liver metastasis: ALT(SGPT) <= 5 X ULN. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection requiring hospitalization; psychiatric illness/social situations that would limit compliance with study requirements. * Exclusion of patients with creatinine >2.0 and bilirubin > 2.0. * Pregnant or lactating women. * Patients with a history of bone marrow transplant within the previous two years. * Patients with a known hypersensitivity to any of the components of the drug products. * Patients with major surgery within 30 days prior to entering the study. * Patients with a baseline QTc > 500 ms. * Patients who are unable to swallow pills.

Study Objectives RATIONALE: Drugs used in chemotherapy, such as Gliadel wafer and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy and temozolomide after surgery and Gliadel wafer may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying the side effects of fluorescence-guided surgery with 5-ALA given together with Gliadel wafer, followed by radiation therapy and temozolomide, in treating patients with primary glioblastoma. Conditions: Glioblastoma Intervention / Treatment: DRUG: 5-ALA, DRUG: Gliadel wafers, RADIATION: Radiotherapy as normal based on standard clinical protocols determined by the neuro-oncologist, DRUG: Concomitant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist, DRUG: Adjuvant chemotherapy as normal based on standard clinical protocols determined by the neuro-oncologist Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

INCLUSION CRITERIA i. The patient is reviewed at a specialist neuro-oncology multi-disciplinary team (MDT). ii. Stealth MRI (neuronavigation) will be performed prior to surgery. iii. Imaging is evaluated by a neuro-radiologist and judged to have typical appearances of a primary GBM iv. Radical resection is judged to be realistic by the neurosurgeons at the MDT (i.e. NICE criteria for the use of Carmustine wafers can be met) v. WHO performance status 0 or 1 vi. Age ≥18 vii. Patient judged by MDT to be fit for standard radical aggressive therapy for GBM (resection followed by RT with concomitant and adjuvant temozolomide) EXCLUSION CRITERIA i. GBM thought to be transformed low grade or secondary disease ii. The patient has not been seen by a specialist MDT. iii. There is uncertainty about the radiological diagnosis iv. 5-ALA or Carmustine wafers is contra-indicated (inc known or suspected allergies to 5-ALA or porphyrins, or acute or chronic types of porphyria) v. Pregnant or lactating women vi. Known or suspected HIV or other significant infection or comorbidity that would preclude radical aggressive therapy for GBM vii. Active liver disease (ALT or AST ≥5 x ULRR) viii. Concomitant anti-cancer therapy except steroids ix. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years x. Previous brain surgery (including biopsy) or cranial radiotherapy xi. Platelets <100 x109/L xii. Mini mental status score <15

Study Objectives The purpose of this study is to evaluate two different dosing regimens of LY2334737 in participants with cancer that is advanced and/or has spread to other parts of the body. Information about side effects will be collected. Conditions: Malignant Solid Tumor, Solid Tumor, Metastatic Tumor Intervention / Treatment: DRUG: LY2334737 Location: United States, France, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of advanced and/or metastatic cancer (including lymphoma) for which no treatment of higher priority exists * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Estimated life expectancy of more than 12 weeks * Have discontinued all previous therapies for cancer for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) and recovered from acute effects of therapy * Have discontinued radiotherapy more than one week before enrolling in the study and have recovered from the acute effects of therapy * Have adequate organ function * Follow your doctor's directions and live close enough to the study site so you can continue to go to the clinic for follow-up * Are willing and able to swallow capsules and follow study procedures * Have given written informed consent prior to any study-specific procedures * Males and females with reproductive potential should use medically approved contraceptive precautions during the study and for 6 months following the last dose of study drug * Females with child-bearing potential must have had a negative urine or serum pregnancy test 7 days prior to the first dose of study drug Exclusion Criteria: * Have gastrointestinal diseases or prior surgery that may interfere with the absorption of medication taken by mouth * Females who are pregnant or lactating * Symptomatic central nervous system malignancy or metastasis * Known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) * Liver cirrhosis or chronic hepatitis * Acute or chronic leukemia * Are currently receiving treatment with valproic acid (VPA) and its derivatives, or if you have a history of intolerance to VPA * Known hypersensitivity to gemcitabine

Study Objectives There is a direct association between cancer and thrombosis (blood clots). The purpose of this study is to determine the best dose of an antithrombotic (prevents blood clots) agent called fondaparinux in non-small cell lung cancer(NSCLC). Patients will also receive chemotherapy. Conditions: Non-Small Cell Lung Cancer, Venous Thromboembolism Intervention / Treatment: DRUG: Combination of Arixtra with chemotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic or cytologic diagnosis of Non-Small Cell Lung Cancer. * Stage IV Non-Small Cell Lung Cancer. * Measurable or assessable tumor parameters according to RECIST criteria. * ECOG Performance Status 0-2. * Age between 18 and 79 years (in the State of Alabama > 18). * Adequate hematologic, coagulation, liver and renal function, defined as: * Absolute neutrophil count (ANC) ≥ 1500/µL * Platelet count ≥ 100,000/µL * Serum Glutamic Oxaloacetic Transaminase(SGOT)/Serum Glutamic Pyruvic Transaminase(SGPT) ≤ 2.5 x upper limit of normal or ≤ 5 x upper limit of normal when liver metastases are present * Total bilirubin value ≤ 1.5 x upper limit of normal * Serum creatinine value ≤ 1.5 x upper limit of normal * Normal prothrombin time and partial thromboplastin time * Fully recovered from any previous surgery (at least 4 weeks since major surgery). * Must have recovered from prior radiation therapy (at least 3 weeks). * All participants must agree to practice approved methods of birth control (if applicable). A negative pregnancy test must be documented during the screening period for women of childbearing potential. * Must provide written informed consent and authorization to use and disclose health information. * No prior chemotherapy. Exclusion Criteria: * Active bleeding disorder. * Evidence of hemoptysis. Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24-hour period in the best estimate of the investigator. * Previous history of Venous Thromboembolism (VTE) within 12 months and requiring active anticoagulation therapy. * Concurrent cancer chemotherapy, biologic therapy or radiotherapy. * Administration of any investigational drug within 28 days prior to administration of the current therapy. * Symptomatic brain metastases; those patients should be treated first with either whole brain radiation therapy or radiosurgery and have stable disease. * Concurrent serious infection. * Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor, which is likely to compromise patient safety and affect the outcome of the study. * History of other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for a minimum of 2 years. * Any evidence or history of hypersensitivity or other contraindications for the drugs used in this trial. * Psychiatric disorder that prevents patients from providing informed consent or following protocol instructions. * Pregnant or lactating women. * Creatinine clearance < 30 mL/min. * Patient body weight < 50 kg.

Study Objectives The purpose of this study is to evaluate efficacy and safety of the combination regimen of bortezomib-bendamustine-dexamethasone in patients with relapsed or refractory multiple myeloma Conditions: Multiple Myeloma Intervention / Treatment: DRUG: bendamustine plus bortezomib plus dexamethasone Location: Czech Republic, Austria Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age min. 18 years at the time of signing the informed consent form * Life expectancy of at least 3 months * Able to adhere to the study visit schedule and other protocol requirements * Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements: Serum M-protein ≥ 10g/l; Urine light-chain (M-protein) of ≥ 200 mg/24 hours; Serum FLC assay: involved FLC level ≥10 mg/dl provided sFLC ratio is abnormal * Relapsed or refractory MM in stage II or III after autologous SCT or conventional chemotherapy (histologically or cytologically proven/ Salmon and Durie criteria) in need of therapy * All previous cancer therapy, including cytostatic therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study, except corticosteroid therapy (dosage 40 to max. 160mg). Localised radiation therapy is allowed, but the increased risk of leukocytopenia, erythrocytopenia and thrombocytopenia based on the combination of a polychemotherapy and radiation therapy has to be considered and a close monitoring of the patients has to be assured. * ECOG performance status of 0-2 at study entry * Laboratory test results within these ranges: * Absolute neutrophil count min. 1.5 x 109/L * Platelet count min. 75 x 109/L * Total bilirubin max. 1.5 mg/dL * AST (SGOT) and ALT (SGPT) max. 2 x ULN or max. 5 x ULN if hepatic lesions are present. * Disease free of prior malignancies for min. 5 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast * Fertile patients must use effective contraception during and for 6 months after study treatment No study treatment or any other procedure within the framework of the trial (except for screening) will be performed in any patient prior to receipt of written informed consent. Exclusion Criteria: * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form * Pregnant or breast feeding females * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by NCI CTCAE, version 3.0. * Use of any other experimental drug or therapy within 28 days of pre-study visit. * Known hypersensitivity to the study drugs * Any prior use of bortezomib or bendamustine in the last six months * Concurrent use of other anti-cancer agents or treatments other than those stated in this treatment plan * Known positive for HIV or infectious hepatitis, type A, B or C * Active, uncontrolled infections * Acute diffuse infiltrative pulmonary disease and pericardial disease.

Study Objectives The aim of this prospective, observational study is the evaluation of the effectiveness of a 14-day Specialist Palliative Care therapy in participants with advanced breast cancer carried out in a stationary palliative care unit in Poland. The length of the entire study will be 36 months. Conditions: Breast Cancer, Palliative Care, Quality of Life, Cancer, Breast Intervention / Treatment: PROCEDURE: Specialist Palliative Care Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: the patient's conscious consent for examination and the ability to fill in the form by the patient herself. * Exclusion Criteria: * patients with cognitive disturbances disabling credible answers in the questionnaire, deceased patients or those discharged from the ward before 14 days of hospitalisation.

Study Objectives A distinctive subtype of gastric adenocarcinoma with extensive bone marrow metastasis and DIC has been described. Few patients have been treated properly due to the lack of standard care. We designed this phase II study to evaluate a dose-dense regimen for this kind of highly aggressive gastric cancer (HAGC). Conditions: Gastric Cancer, Bone Marrow Metastasis, Disseminated Intravascular Coagulation Intervention / Treatment: DRUG: 5-fluorouracil, DRUG: Docetaxel Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * ECOG PS 0-3; * Pathologically confirmed adenocarcinoma in stomach or esophagogastric junction; * Bone marrow metastasis confirmed by aspiration, biopsy or PET/CT scan; * overt DIC according to the International Society on Thrombosis and Haemostasis (ISTH) criteria; * Treatment-naive after the diagnosis of metastasis; * Platelet ≤ 50 \* 10E9/L; * ALT≤5×ULN, AST≤5×ULN, Bilirubin≤5×ULN, Creatinine≤3×ULN; * Written informed consent. Exclusion Criteria: * Concurrent aggressive malignancy; * Docetaxel containing perioperative treatment within 6 months; * Allergic to the study drugs; * Serious medical conditions, including severe heart disease, severe cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled infection,etc. * HIV positive; * MSI-H; * Her-2 gene overexpression; * Inadequate contraceptive measures.

Study Objectives This phase II trial studies the side effects of giving intensity-modulated radiation therapy together with cisplatin and bevacizumab followed by carboplatin and cisplatin and to see how well they work in treating patients who have undergone surgery for high-risk endometrial cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving intensity-modulated radiation therapy together with chemotherapy and bevacizumab after surgery may kill any tumor cells that remain after surgery. Conditions: Endometrial Adenocarcinoma, Endometrial Adenosquamous Carcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Stage IA Uterine Corpus Cancer AJCC v7, Stage IB Uterine Corpus Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7, Stage IIIA Uterine Corpus Cancer AJCC v7, Stage IIIB Uterine Corpus Cancer AJCC v7, Stage IIIC Uterine Corpus Cancer AJCC v7, Stage IVA Uterine Corpus Cancer AJCC v7, Stage IVB Uterine Corpus Cancer AJCC v7 Intervention / Treatment: BIOLOGICAL: Bevacizumab, DRUG: Carboplatin, DRUG: Cisplatin, RADIATION: Intensity-Modulated Radiation Therapy, DRUG: Paclitaxel Location: United States, Hong Kong, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed endometrial cancer, including 1 of the following cellular types: * Endometrioid endometrial adenocarcinoma * Clear cell carcinoma * Papillary serous adenocarcinoma * Adenosquamous cell carcinoma * Other adenocarcinoma variant * No carcinosarcoma * Meets 1 of the following criteria: * Grade 3 carcinoma with > 50% myometrial invasion (stage IC or IIA) (all papillary serous or clear cell carcinoma will be considered grade 3) * Grade 2 or 3 carcinoma with any cervical stromal invasion (stage IIB) * Known extra-uterine disease confined to the pelvis (stage III or IVA) * Patients with stage III or IVA disease must have undergone computed tomography (CT) scan or positron emission tomography (PET)/CT scan of the abdomen and pelvis within the past 56 days * Has undergone hysterectomy (i.e., total abdominal, vaginal, robotic-assisted, radical, or laparoscopic-assisted vaginal hysterectomy) and bilateral salpingo-oophorectomy within the past 56 days * No positive common iliac or positive para-aortic nodal disease (defined as lymph nodes ? 2 cm in any dimension on CT scan or biopsy) or positive peritoneal cytology * No evidence of metastatic extrauterine disease, gross or residual disease (not including pelvic nodal disease), or distant metastases * Zubrod performance status 0-1 * Absolute neutrophil count (ANC) ? 1,500/mm\^3 (without growth factor support) * Platelet count ? 100,000/mm\^3 * Hemoglobin ? 10 g/dL (transfusion allowed) * Total bilirubin ? 1.5 times upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2 times ULN * Serum creatinine ? 1.5 mg/dL * Urine protein:creatinine ratio ? 0.5 OR urine protein < 1,000 mg on 24-hour urine collection * International normalized ratio (INR) < 1.5 (for patients treated with warfarin within the past 14 days) * Not nursing * No neuropathy ? Common Terminology Criteria for Adverse Events (CTCAE) grade 1 * No ototoxicity > CTCAE grade 2 * No serious, active comorbidity, including any of the following: * Unstable angina and/or New York Heart Association (NYHA) class II-IV congestive heart failure requiring hospitalization within the past 12 months * Transmural myocardial infarction within the past 12 months * Acute bacterial or fungal infection requiring IV antibiotics * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition (human immunodeficiency virus \[HIV\] testing is not required) * Active gastrointestinal (GI) ulcers, GI bleeding, inflammatory bowel disease, or GI obstruction * Inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications * Significant vascular disease, including aortic aneurysm, aortic dissection, or arteriovenous malformation within the past 12 months * Serious cardiac arrhythmia on medication (well-controlled atrial fibrillation on medication allowed) * Serious non-healing wound, ulcer, or bone fracture * No history of hypertensive crisis or hypertensive encephalopathy * No stroke/cerebrovascular event within the past 12 months * No arterial thromboembolic events, including transient ischemic attack or clinically symptomatic peripheral artery disease within the past 12 months * No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 6 months * No other invasive malignancies within the past 3 years other than nonmelanomatous skin cancer * No significant trauma within the past 28 days * No mental status changes or bladder problems that would preclude the ability to comply with bladder-filling instructions * No mental or psychiatric illness that would preclude giving informed consent * No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies * No prior allergic reaction to bevacizumab, cisplatin, carboplatin, or paclitaxel * No concurrent erythropoietin, St. John's wort, therapeutic anticoagulants, aminoglycoside antibiotics, or amifostine * No prior organ transplantation * No prior external-beam radiotherapy to the pelvis resulting in overlapping of radiotherapy fields * No prior systemic chemotherapy for uterine cancer * Prior chemotherapy for a different cancer is allowed * No prior therapy with anti-vascular endothelial growth factor (VEGF) compounds * More than 28 days since prior major surgical procedure requiring open biopsy incision * No concurrent surgery (except for vascular access device placement or procedures that do not require significant incision) * No concurrent warfarin at doses > 1 mg/day * Concurrent prophylactic low molecular weight heparin allowed

Study Objectives The purpose of this first-in-man study is to evaluate safety, tolerability and pharmacokinetics of ODM-204 in patients with metastatic castration-resistant prostate cancer. Conditions: Prostate Cancer Intervention / Treatment: DRUG: ODM-204, DRUG: Prednisone Location: United Kingdom, Finland, Latvia, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Written informed consent (IC) obtained. * Male aged ≥ 18 years. * Histologically or cytologically confirmed adenocarcinoma of prostate. * Ongoing GnRH agonist or antagonist therapy, or after bilateral orchiectomy. * Progressive metastatic disease * Adequate bone marrow, hepatic, and renal function * Acceptable and regular bowel movements without any GI disorder or procedure which may interfere with absorption of study treatment * Ability to swallow study treatments Exclusion Criteria: * History of pituitary or adrenal dysfunction. * Known brain metastases. * Active infection or other medical condition that would make prednisone (corticosteroid) contraindicated. * Uncontrolled hypertension * Clinically significant heart disease * Prolonged QTc interval

Study Objectives This phase I trial studies the side effects and best dose of ipilimumab and imatinib mesylate in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ipilimumab and imatinib mesylate may work better in treating patients with solid tumors. Conditions: Advanced Malignant Solid Neoplasm, C-KIT Tyrosine Kinase Protein Overexpression, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Gastrointestinal Stromal Tumor, Metastatic Malignant Solid Neoplasm, Metastatic Melanoma, Pathologic Stage IV Cutaneous Melanoma AJCC v8, Unresectable Melanoma, Unresectable Solid Neoplasm Intervention / Treatment: DRUG: Imatinib Mesylate, BIOLOGICAL: Ipilimumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * For dose escalation study, patients must have histological confirmation of solid tumors that is metastatic or unresectable. For expansion cohorts, patients must have metastatic or unresectable gastrointestinal stromal tumor (GIST), melanoma, or uncategorized tumors with tumor biopsies that are positive for c-KIT mutations by polymerase chain reaction (PCR) or immunohistochemistry (IHC). For patients enrolled in the melanoma expansion cohort, only select KIT mutations will be eligible. Patients with mutations in exon 13 V654X, 14 T6701, 17 D816X and all exon 18 mutations will not be eligible for enrollment. * Patients who have completed previous therapies 4-weeks prior to (or within 5 drug half lives) enrollment on study. Radiation therapy wash out period will be 2 weeks. This includes an exception of patients with metastatic GIST tumors who are taking maintenance imatinib mesylate therapy. These patients are allowed to remain on imatinib mesylate therapy up to enrollment in this study. * Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%). * Leukocytes > 3,000/mcL * Absolute neutrophil count > 1,500/mcL * Platelets > 100,000/mcL * Total bilirubin < or = 2.0 mg/dL. (Does NOT apply to patients with Gilbert's syndrome) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) < 2.5 X institutional upper limit of normal (patients with liver involvement will be allowed < or = 5.0 X institutional upper normal limit) * Serum creatinine < 2.0 mg/dL * Patients MUST have recovered from all treatment related toxicities to grade 1 National Center Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version \[v\] 4.0) in severity. * Patients must be willing and able to review, understand, and provide written consent before starting therapy. * Patients with histologically proven intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma will be eligible. Patients must have shown unequivocal radiographic evidence for tumor progression by magnetic resonance imaging (MRI) scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required. * Patients in the expansion cohort must also agree to participate in the biomarker study. However, patients in the melanoma KIT positive mutant subgroup, patients must agree to participate in the biomarker study and biopsies. * Patients must be willing to stay within 2 hours drive of MD Anderson Cancer Center whilst receiving Ipilimumab therapy. Patient must also agree to present to MD Anderson emergency center while on Ipilimumab therapy. Exclusion Criteria: * Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus or autoimmune vasculitis \[e.g., Wegener's granulomatosis\] are excluded from this study. * History of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation. * Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs): e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. * Any non-oncology live vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab). * Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (when used in the management of cancers other than intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma, or when used to treat non-cancer-related illnesses). * Patients who do not agree to practice appropriate birth control methods while on therapy. * Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician.

Study Objectives Study A536-05 is an open-label extension study for patients previously enrolled in study A536-03 (ClinicalTrials.gov Identifier NCT01749514), to evaluate the long-term safety and tolerability of ACE-536 in patients with low or intermediate-1 risk MDS. Conditions: Myelodysplastic Syndromes Intervention / Treatment: DRUG: ACE-536 Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Completion of the treatment period in the base study A536-03 (ClinicalTrials.gov Identifier: NCT01749514) * Adequate birth control measures * Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements. * Patient understands and is able to provide written informed consent. In addition, patients with treatment interruption (defined as patients who complete their end-of-study visit in A536-03 and cannot directly roll over to A536-05) must also meet the following criteria: * Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) criteria 2 (white blood count (WBC) < 13,000/μL) that meets International Prognostic Scoring System (IPSS) classification (Appendix 2) of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening; * Anemia defined as: * Mean hemoglobin concentration < 10.0 g/dL of 2 measurements (one performed within one day prior to Cycle 1 Day 1 and the other performed 7-28 days prior to Cycle 1 Day 1), for non-transfusion dependent (NTD) patients (defined as having received ˂ 4 units of red blood cells (RBCs) within 8 weeks prior to Cycle 1 Day 1), OR * Transfusion Dependent (TD), defined as having received ≥ 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1. * Platelet count ≥ 30 x 109/L * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia) * Adequate renal (creatinine ≤ 2.0 x upper limit of normal \[ULN\]) and hepatic (total bilirubin < 2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN) function Exclusion Criteria: * Discontinuation/withdrawal from the base study A536-03 (due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication \[e.g. azacitidine\], medical reason or adverse event (AE), hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up) prior to completion of the treatment period * Prior treatment with azacitidine or decitabine * Treatment within 28 days prior to Cycle 1 Day 1 with: * an erythropoiesis-stimulating agent (ESA), * Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF), * Lenalidomide * Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1 * Treatment with another investigational drug (including sotatercept \[ACE-011\]) or device, or approved therapy for investigational use ≤ 28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer * Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1 * Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV) * Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg * Pregnant or lactating females * History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug * Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study

Study Objectives The purpose of this study is to determine if CNTO 888 is safe and to determine how long CNTO 888 stays in the body and what effects it might have on cancer tumors. Conditions: Cancer Intervention / Treatment: DRUG: CNTO 888 Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with solid tumors that have progressed on or after all available standard therapy * Histological or cytological documentation of specific tumor type * Evidence of measurable or evaluable metastatic disease * Anticipated life expectancy is >= 12 weeks Exclusion Criteria: * Treatment with systemic cancer therapy or local radiotherapy within 4 weeks * Received any investigational drug/agent within 4 weeks * Major surgery within 4 weeks of first dose of study agent * Serious concurrent illness (medical or psychiatric), altered mental status (eg, dementia) or any uncontrolled medical condition (eg, uncontrolled diabetes).

Study Objectives The investigators will be retrospectively review the case note of patients registered in the EAP of Nivolumab. A standard anonymous data collection form will be used to collect data and to analyze it. Patients with advanced Non-Small Cell Lung Cancer previously treated and included in the SPANISH expanded access programme of nivolumab. Conditions: Non Small Cell Lung Cancer Intervention / Treatment: DRUG: Nivolumab 10 MG/ML Location: Spain Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Squamous or Non-Squamous, non small cell lung cancer (NSCLC), Stage IIIb/IV (histologically or cytologically confirmed), relapsed after 1 prior platinum-based systemic treatment and who received treatment within the SPANISH expanded access programme of nivolumab (EAP) * Alive patients must have signed and dated an IRB/IEC-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care Exclusion Criteria: * Alive patients who do not want to sign and date an IRB/IEC-approved written informed consent form * Patients who were accepted in the EAP but do not receive treatment

Study Objectives To determine the maximum tolerated dose of a densified regimen of the association of docetaxel (DTX) and epirubicin (EPI), supported by the concomitant administration of hematopoietic growth factors in patients with metastatic breast cancer in first-line, optimizing in each patient the administration schedule using a formal procedure based on mathematical models in order to manage the severity of induced neutropenia. The models used in this project allow: * an optimal administration schedule of the planned total dose per cycle (number of infusions and calculating their rates and durations) * an individualization of the administration schedule from the second cycle (based on observations from the first cycle), and * an assessment of the risk of a dose-limiting toxicity event combining several severe non-hematological toxicities (conditioning the decision for dose escalation). Using formal mathematical models the investigators expect controlling the hematological and non-hematological toxicities in order to realize the full series of six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient. For each patient, chemotherapy is considered feasible if it is possible, in the absence of tumor progression, to consider 6 cycles of treatment without observing any serious adverse events and without: * patient death that may be related to the treatments; * decision of the patient to interrupt treatment for physical or psychological tolerance reasons; * decision of the investigator to discontinue treatment, in the absence of disease progression. Conditions: Metastatic Breast Cancer Intervention / Treatment: DRUG: Combination of Docetaxel (DTX) and Epirubicin (EPI) Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age ≥ 18 years, * ECOG performance status ≤ 2 * Diagnosed with metastatic HER2-negative hormone-resistant chemotherapy-naive breast cancers, previous adjuvant chemotherapy treatment are allowed. * Histologically or cytologically proven breast cancer metastases or associated with CA 15-3 levels 50% above the normal value * Hormone resistance defined by the presence of negative hormone receptors or disease progression within 6 months of the initiation of hormone therapy. * Adequate renal and liver function (ASAT and ALAT < twice the upper limit normal value (ULN) if no liver metastases, or < 4×ULN if liver metastases; total bilirubin < 2×ULN), * Adequate cardiac function (left ventricular ejection fraction (LVEF) > 50%), * Neutrophils ≥ 1200/mm3 * Platelets ≥ 105/mm3 Exclusion Criteria: * Cerebral metastases and meningeal involvement, * Other malignant diseases, * Significant comorbidities, * Previous chemotherapy for metastatic disease, or previous chemotherapy with a total cumulative dose greater than 600 mg/m² for EPI or greater than 450 mg/m² for DTX

Study Objectives This is a non-randomized, open-label, multi-site study to collect safety and efficacy data on an intraoperative imaging system, the LUM Imaging System (LUM015 imaging agent in conjunction with the LUM imaging device), in identifying residual cancer in the tumor bed of female breast cancer patients. During the study, study physicians and clinical staff will complete hands-on training in anticipation of the upcoming pivotal study. Site-specific or user-specific issues related to the use of the device will be identified and addressed. Additionally, the data collected in the study will be used to continue training the tumor detection algorithm of the device. In this study, patients will be injected with LUM015 prior to surgery. The study physicians will perform lumpectomy procedures according to his or her institution's standard of care practice. After the main specimen removal is completed, the study physician will use the LUM Imaging Device to image the tumor bed. Therapeutic shaves will be removed based on the recommendation of the LUM Imaging System. Patients will be followed until their first standard of care post-operative follow-up visit. Conditions: Breast Cancer Intervention / Treatment: COMBINATION_PRODUCT: LUM Imaging System Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: OTHER Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Subjects must have histologically or cytologically confirmed primary invasive breast cancer, ductal carcinoma in situ (DCIS) or a combination of invasive breast cancer and DCIS. The protocol accepted methods for obtaining the histological samples are diagnostic core needle biopsies or fine needle biopsies. * Female, age of 18 years or older. Because no dosing or adverse event data are currently available on the use of LUM015 in subjects <18 years of age, children are excluded from this study. * Subjects must be scheduled for a lumpectomy for a breast malignancy. * Subjects must be able and willing to follow study procedures and instructions. * Subjects must have received and signed an informed consent form. * Subjects must have no uncontrolled serious medical problems except for the diagnosis of cancer, as per the exclusion criteria listed below. * Subjects must have normal organ and marrow function within limits as defined below: * Leukocytes > 3,000/mcL * Platelets > 75,000/mcL * total bilirubin within normal institutional limits * AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal * Creatinine ≤ 1.5 mg/dL or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. Exclusion criteria: * Subjects who are treated for bilateral breast cancer resection procedure. * Subjects who are pregnant at the time of diagnosis of their breast cancer; this exclusion is necessary because the teratogenic properties of LUM015 are unknown. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with LUM015, breastfeeding should be discontinued if the mother is treated with LUM015. * Subjects who are sexually active and not willing/able to use medically acceptable forms of contraception (hormonal or barrier method of birth control, abstinence) upon entering the study and for 60 days after injection of LUM015. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Breast cancer patients are routinely advised against becoming pregnant during treatment, so this requirement does not differ from standard of care. * Subjects who have taken an investigational drug within 30 days of enrollment. * Subjects with prolonged QTc interval defined as greater than 480 ms. * Subjects who will have administration of methylene blue or any dye for sentinel lymph node mapping on the day of the surgery prior to imaging the lumpectomy cavity with the LUM Imaging Device. * Subjects who have not recovered from adverse events due to other pharmaceutical or diagnostic agents. * Subjects with uncontrolled hypertension defined as persistent systolic blood pressure > 180 mm Hg, or diastolic blood pressure > 110 mm Hg; those subjects with known HTN should be stable within these ranges while under pharmaceutical therapy. * History of allergic reaction attributed to drugs containing polyethylene glycol (PEG). * History of allergic reaction to any oral or intravenous contrast agents. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, COPD or asthma requiring hospitalization within the past 12 months, or psychiatric illness/social situations that would limit compliance with study requirements. * HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with LUM015. * Any subject for whom the investigator feels participation is not in the best interest of the subject. * Subjects undergoing a second lumpectomy procedure because of positive margins in a previous surgery prior to entering this study. * Subjects with prior ipsilateral breast cancer surgeries, mastectomies, breast reconstructions or implants. * Subjects who have undergone a surgical biopsy for any reason in the ipsilateral breast performed less than 2 years prior to enrollment of this study. * Subjects with prior ipsilateral reduction mammoplasties (breast reductions) performed less than 2 years prior to enrollment to this study. * Subjects previously treated with systemic therapies to treat the cancer to be removed during this clinical investigation, such as neo-adjuvant chemotherapy or hormonal therapy. * Subjects undergoing breast conserving surgery whose resected specimen will be evaluated with frozen section.