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Study Objectives The purpose of this study is to determine whether Vitamin D supplementation reduces the symptoms of muscle stiffness and joint tenderness that some patients may develop after starting therapy with Anastrozole for breast cancer. Conditions: Breast Neoplasms Intervention / Treatment: DIETARY_SUPPLEMENT: Vitamin D, DIETARY_SUPPLEMENT: Calcium carbonate, DRUG: Vitamin D, OTHER: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: FACTORIAL Masking: TRIPLE

Inclusion Criteria * Women with a diagnosis of hormone receptor positive invasive breast cancer (Stage I-IIIB) or ductal carcinoma in situ (DCIS) * Postmenopausal status * Completed at least 8 weeks of anastrozole as adjuvant therapy prior to study entry * Completed systemic chemotherapy and radiation treatments when indicated * Serum Calcium <= 10.3 mg/dL * Patients with marginal 25 OH Vitamin D level (between 10 and 29 ng/ml) will be in the Randomized Group or Low 25 OH Vitamin D level (less than 10 ng/ml) will be in Observational Group * 24-hour urine Calcium excretion <= 250 mg/g (calculated by dividing 24 hour calcium by 24 hour creatinine) * A history of generalized musculoskeletal pain with or without localized regions or discomfort that has developed or worsened since starting adjuvant aromatase inhibitor therapy Exclusion Criteria * Known metastatic disease * History of kidney stones * History of active primary hyperparathyroidism * History of Paget's disease of the bone * History of severe arthritis, rheumatoid arthritis, or severe neuropathy * Normal 25 OH Vitamin D level (>= 30 ng/ml) * Medical or psychiatric condition which may preclude protocol compliance

Study Objectives The purpose of this study is to determine if vitamin D will improve insulin resistance, inflammation, and overall well-being in women with PCOS. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DIETARY_SUPPLEMENT: Vitamin D, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Diagnosis of PCOS based on: * Eight or fewer menstrual periods per year or spontaneous intermenstrual periods of greater than or equal to 45 days, and * Elevated testosterone levels Exclusion Criteria: * Current Pregnancy or Nursing * Elevated calcium * Kidney Stones or kidney disease * Current use of vitamin D (other than a multivitamin) * Use of metformin or other insulin sensitizing drugs in the last 3 months * Elevated prolactin or untreated thyroid disease * Diabetes, Liver disease, Heart disease, or other serious medical condition

Study Objectives The goal of the study is to learn about patients' knowledge of their medications in an outpatient acute care setting (such as the M. D. Anderson Emergency Center) and to learn about any clinical factors that affect patients' knowledge of their medications. Conditions: Advanced Cancer Intervention / Treatment: BEHAVIORAL: PMKT Questionnaire Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients admitted to the Emergency Center * Patients must be able to read and write English * Patients must agree to participate and sign informed consent * Patients 16 years or above. (Age limit explained below) * Patients must be able to complete the survey tool. They may have help from a caregiver in transcribing the information but the caregiver can not fill the tool independent of the patient. A research assistant will be trained to discriminate whether a caregiver is acting as a scriber or independently completing the tool. If the caregiver completes the tool independently, the patient will be excluded from the study. Exclusion Criteria: * Patients with altered mental status and those with an acute, emergent illness and hemodynamic instability (Examples: status epileptics, sepsis, and cardiac arrest) * Employees of the institution with work-related injuries * Visitors who are non-cancer patients * Patients transferred directly from another hospital * Patients will be excluded after their first enrollment during the study period. (Can only be enrolled once though may have multiple Emergency Center visits during study time frame). * Patients will be excluded if all prescribed medications are filled at an external pharmacy and this pharmacy is not accessible.

Study Objectives The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. This approach is biologically directed to overall target the cancer cell at multiple levels, and potentially preventing chemotherapy and EGFR-therapy resistance. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: Irinotecan, BIOLOGICAL: Cetuximab, BIOLOGICAL: RAD001 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Histological or cytological proof of colon or rectal adenocarcinoma * Measurable site of disease according to RECIST that has not been previously irradiated * Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab * Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 *28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.) * A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer * Prior radiation therapy allowed to < 25% of the bone marrow * Age >= 18 years at the time of consent * Written informed consent and HIPAA authorization for release of personal health information * Females of childbearing potential and males must be willing to use an effective method of contraception * Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy Exclusion Criteria: * No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy * No prior treatment with cetuximab * No prior treatment with an mTOR inhibitor * No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients * No treatment with any investigational agent within 28 days prior to being registered for protocol therapy * No symptomatic brain metastasis * No uncontrolled diabetes as defined by a fasting serum glucose >1.5 x ULN * No chronic treatment with systemic steroids or another immuno-suppressive agent * No serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy * No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis * No active bleeding or a pathological condition that is associated with a high risk of bleeding * No uncontrolled systemic disease including active infections or uncontrolled hypertension * No known history of HIV seropositivity * No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy * No planned immunization with attenuated live viruses during the study period * Females must not be breastfeeding

Study Objectives A study to determine the safety of CSC/ HTS-based combination drug therapy in subjects who have GBM that has recurred or progressed following prior radiation therapy and TMZ. Conditions: Glioblastoma Multiforme Intervention / Treatment: DRUG: Combination Drug Therapy 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: Determined at pre-screening: * A histological diagnosis of GBM [WHO grade IV]. * Subjects >=18 years * Signed informed consent for tumor collection prior to initiation of any study-specific procedure. The patient or the patient's legal authorized representative must be able to provide written informed consent (ICF) and understand the potential risks and benefits from study enrollment and treatment * Patients must have a life expectancy of >12 weeks Determined at or around surgery, and prior to performing HTS: * Patients must have a surgically accessible tumor with the intent for a gross or near total resection of the tumor mass (GBM, WHO grade IV) * Collection of sufficient tumor material for processing CSCs Determined at or around tumor recurrence, and after completion of HTS: * Disease progression following radiation and TMZ therapy (as defined by RANO criteria (45); Appendix 3). Unlimited relapses are allowed, provided the functional status and other eligibility criteria for enrollment are met Determined at baseline: * Signed informed consent for CSC/HTS based therapy prior to initiation of any study-specific procedure or treatment. The patient or the patient's legal authorized representative must be able to provide written informed consent (ICF) and understand the potential risks and benefits from study enrollment and treatment * Patients must have a KPS rating of >=70 (see Appendix 4: Karnofsky Performance Scale) * Patients must have recovered from the toxic effects of prior therapy to < Grade 2 toxicity per NCI CTCAE version 4 (Appendix 6) prior to Day 1 of Cycle 1. The minimum duration required between prior therapy and initiation of study drug treatment is as follows: * At least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence (such as histological confirmation) in which case at least 4 weeks from completion of radiation will suffice * 4 weeks from prior cytotoxic chemotherapy * 4 weeks from prior experimental drug * 6 weeks from nitrosoureas * 3 weeks from procarbazine * 1 week for non-cytotoxic agents. * Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria: * Hemoglobin (Hgb)> 8 g/dL * Absolute Neutrophil Count (ANC) > 1,000/mm3 * Platelet count > 100,000/mm3 * Creatinine < 2 mg/dL * Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3x upper limit of normal (ULN) * Patients of childbearing potential must agree to use an adequate method of contraception for the duration of the study, and for 90 days following discontinuation of study drugs * Females of childbearing potential must have a negative pregnancy test * Patients must be negative for HIV, Hepatitis B and C * Patients are cooperative and able to complete all the assessment procedures. Exclusion Criteria: * Any condition, including the presence of clinically significant laboratory abnormalities, which places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study * Active infection, (including known Acquired Immunodeficiency Syndrome (AIDS) and Hepatitis C) within 3 days prior to the study enrollment * Diseases or conditions that obscure toxicity or dangerously alter drug metabolism * Serious intercurrent medical illness (e.g., symptomatic congestive heart failure) * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent unless they have a legal authorized representative that can consent on their behalf * Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 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 6 months * History of stroke or transient ischemic attack within 6 months * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months * History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month. * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). * Grade 2 or higher peripheral neuropathy per NCI CTCAE version 4 * History of abdominal fistula or gastrointestinal (GI) perforation within 6 months. * Serious, non-healing wound, active ulcer, or untreated bone fracture * Allergies to reagents used in this study * Women of child bearing age not willing to use a reliable form of contraception * Pregnancy (positive pregnancy test) or lactation * Patient is positive for HIV, Hepatitis B or C * Concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) Patients must discontinue an EIAED at least two weeks prior to starting study drug * Concurrent use of herbal medications * Patient is simultaneously participating in another clinical trial during the Phase 1 (treatment phase) of this study. Patients may enroll/consent in the Phase 0 portion of this study for tissue collection and HTS while being treated with standard of care or clinical trial for newly diagnosed GBM prior to recurrence. Inability or unwilling to comply with protocol or study procedures.

Study Objectives The main objective of the trial is to document the efficacy of NGR-hTNF administered at low dose weekly in advanced Malignant Pleural Mesothelioma patients previously treated with a pemetrexed-based chemotherapy regimen. Conditions: Malignant Pleural Mesothelioma Intervention / Treatment: DRUG: NGR-hTNF plus Best Investigator's Choice (BIC), DRUG: Placebo plus Best Investigator's Choice (BIC) Location: Egypt, Netherlands, Spain, United Kingdom, Poland, Canada, Ireland, United States, Sweden, Belgium, France, Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Age >= 18 years * Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatoid, mixed, or unknown * Prior treatment with no more than one systemic pemetrexed-based chemotherapy regimen administered for advanced or metastatic disease. Prior use of a biological agent in combination with a pemetrexed-based regimen and prior administration of intrapleural cytotoxic agents are allowed. Patients who have previously received anthracyclines should not receive doxorubicin * ECOG Performance Status 0 - 2 * Life expectancy of >= 12 weeks * Adequate baseline bone marrow, hepatic and renal function, defined as follows: 1. Neutrophils >= 1.5 x 109/L; platelets >= 100 x 109/L; hemoglobin >= 9 g/dL 2. Bilirubin <= 1.5 x ULN 3. AST and/or ALT <= 2.5 x ULN in absence of liver metastasis or <= 5 x ULN in presence of liver metastasis 4. Serum creatinine < 1.5 x ULN * Measurable or non-measurable disease according to MPM-modified RECIST criteria * Patients may have had prior therapy providing the following conditions are met: 1. Surgery: wash-out period of 14 days 2. Systemic and radiation anti-tumor therapy: wash-out period of 28 days * Patients must give written informed consent to participate in the study Exclusion Criteria: * Patients must not receive any other investigational agents while on study * Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication * Uncontrolled hypertension * QTc interval (congenital or acquired) > 450 ms * History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke) * Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol * Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol * Pregnancy or lactation

Study Objectives This is an open-label, multicenter, Phase 1/2 study of the CTLA-4 antibody, tremelimumab, and the PD-L1 antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator poly-ICLC, a TLR3 agonist, in subjects with advanced, measurable, biopsy-accessible cancers. Conditions: Head and Neck Squamous Cell Carcinoma, Breast Cancer, Sarcoma, Merkel Cell Carcinoma, Cutaneous T-Cell Lymphoma, Melanoma, Renal Cancer, Bladder Cancer, Prostate Cancer, Testicular Cancer, Solid Tumor Intervention / Treatment: DRUG: Durvalumab, DRUG: Tremelimumab, DRUG: Poly-ICLC Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Subjects must have histologic confirmation of advanced, biopsy-accessible, measurable cancers of the following histologies: * Non-viral-associated head and neck squamous cell carcinoma (HNSCC) or human papillomavirus (HPV)-associated HNSCC after failure of prior therapy * Locally recurrent or metastatic breast cancer * Sarcoma * Merkel Cell Carcinoma (MCC) * Cutaneous T cell Lymphoma (CTCL) * Melanoma after failure of available therapies * Genitourinary (GU) cancers with accessible metastases (e.g., bladder, renal) * Any solid tumors with masses that are accessible * Subjects with measurable disease, must have at least 2 lesions (1 measurable lesion and 1 biopsy/injectable lesion, which does not need to be measurable). * Any number of prior systemic therapies. * Eastern Cooperative Oncology Group (ECOG) performance status 0 <= age <= 1. * Laboratory parameters for vital functions should be in the normal range or not clinically significant. Exclusion Criteria: * Prior treatment with combination CTLA-4 and PD-1/PD-L1 blockade, with the exception of subjects with melanoma. * Participants may not have been treated intratumorally with poly-ICLC. * Subjects with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any active brain metastases, or, within 6 months of the first date of treatment on this study, history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage. * Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease or clinically uncontrolled hypertension. * History of pneumonitis or interstitial lung disease or any unresolved immune-related adverse events following prior biological therapy. * Other malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only (e.g., localized low-grade cervical or prostate cancers). * Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition. * Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may be allowed. * History of severe allergic reactions to any unknown allergens or any components of the study drugs. * Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders). * History of allogeneic organ transplant.

Study Objectives Pazopanib (Votrient) is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg once daily (OD) regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of \~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A reduced dose taken with food could be a possible approach to reduce these side effects. Therefore the investigators initially want to determine the equivalent reduced dose of pazopanib when taken with a continental breakfast. Thereafter the investigators want to investigate whether the intake with food reduces the frequently reported side effects nausea and diarrhea. Conditions: Cancer Intervention / Treatment: DRUG: pazopanib, OTHER: continental breakfast Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up. Note: informed consent may be obtained prior to start of the specified screening window. Note: procedures conducted as part of the subject's routine clinical management (e.g. blood count) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol. * >= 18 year old men and women who use pazopanib * Eastern Cooperative Oncology Group (ECOG) performance status of 0 <= age <= 2. * Adequate organ system function Exclusion Criteria: * Poorly controlled hypertension; systolic blood pressure (SBP) >= 40 mm Hg or diastolic blood pressure (DBP) >= 90 mm Hg. Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study. * Corrected QT interval (QTc) > 480msecs. * History of any one or more of the following cardiovascular conditions within the past 6 months: * Cardiac angioplasty or stenting * Myocardial infarction * Unstable angina * Coronary artery bypass graft surgery * Symptomatic peripheral vascular disease * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: * Active peptic ulcer disease * Known intraluminal metastatic lesion/s with risk of bleeding * Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation. * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. * Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: * Malabsorption syndrome. * Major resection of the stomach or small bowel. * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. * Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery). * Evidence of active bleeding or bleeding diathesis. * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. Note: Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessel is acceptable (CT with contrast is strongly recommended to evaluate such lesions). * Recent hemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug). * Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. * Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of day 1 and for the duration of the study. * Concurrent use of other substances known or likely to interfere with the pharmacokinetics of pazopanib. Patients, who are adjusted to proton pump inhibitors and had no dose modifications for over two weeks, are allowed to participate * Women of childbearing potential without adequate contraception, pregnant or breastfeeding women.

Study Objectives This randomized, Phase III, double-blind, placebo-controlled study will evaluate the safety and efficacy of MetMAb (onartuzumab) in combination with Tarceva (erlotinib) compared with treatment with Tarceva alone in patients with incurable Met-positive non-small cell lung cancer (NSCLC). Patients will be randomized in a 2:1 ratio to receive either MetMAb + Tarceva or placebo + Tarceva. Tarceva (150 mg) will be given orally once daily, and MetMAb (15 mg/kg) will be given intravenously every 3 weeks. Treatment will continue until disease progression, unacceptable toxicity, a decision to discontinue, or death occurs. Total study length is expected to be around 36 months. Conditions: Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: erlotinib [Tarceva], DRUG: Placebo, DRUG: Onartuzumab [MetMAb] Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Male or female, >= 18 years. * Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 <= age <= 1. * Histologically confirmed incurable Stage IIIB/IV NSCLC tumor. * Met-positive status and results of epidermal growth factor receptor (EGFR)-activating mutation testing. * Available tumor tissue sample or agreement to take such a sample. * Radiographic evidence of disease. Lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has occurred at that site since radiation. * Prior treatment with at least one platinum-based line of treatment for locally advanced, unresectable/inoperable disease or metastatic disease, and no more than one additional line of chemotherapy treatment, defined as follows: * Adjuvant/neoadjuvant chemotherapy or chemoradiation counts as a line of therapy if < 12 months have elapsed between the last dose and the date of recurrence. Combined treatment with chemotherapy and radiation constitutes a single regimen; surgery is not considered a regimen. * Cytotoxic maintenance therapy that differs from first-line therapy is considered an additional line of therapy. However, changes in treatment due to intolerance or excessive toxicity are not considered an additional regimen. * The last dose of prior chemotherapy must have been given >= 21 days prior to Day 1 (>= 14 days for vinorelbine or other vinca alkaloids or gemcitabine). * Anti-cancer agents used for pleurodesis are not counted as a line of therapy. * Prior radiation therapy is allowed provided the patient has recovered from any toxic effects and >= 7 days have elapsed between the last session and randomization. * Patients must use effective contraception throughout the trial and until 3 months after the last dose. Exclusion Criteria: * More than 30 days expsoure to an EGFR inhibitor or a known EGFR-toxicity resulting in dose modifications. * Prior exposure to agents targeting either the HGF or MET pathway, including but not limited to crizotinib, cabozantinib, ficlatuzumab, rilotumumab, and tivantinib. * Pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently. * Brain metastases or spinal cord compression that were not definitively treated with surgery and/or radiation or that were previously diagnosed and treated without evidence of clinically stable disease for >= 14 days. Patients with treated central nervous system (CNS) metastases who are asymptomatic and on a stable dose of corticosteroid for >= 14 days prior to randomization are eligible. * History of another cancer in the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin cancer, stage I uterine cancer, or other cancers that are curable. * Life expectancy < 12 weeks. * Radiographically visible interstitial lung disease (ILD) or a history of it. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * Inadequate hematologic, biological, or organ function. * Significant history of cardiac disease. * Serious active infection at the time of randomization or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment, including positive HIV or active hepatitis B or C infections, significant gastrointestinal abnormalities, uncontrolled diabetes. * Any inflammatory changes to the surface of the eye. * Inability to take oral medication, need for intravenous alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. * Pregnant or breast-feeding women. * Any major surgery within 2 weeks prior to randomization. * Inability to understand the language(s) in which the HRQOL questionnaires are available.

Study Objectives Raltitrexed is a potent thymidylate synthase (TS) inhibitor. Conversely to 5-fluorouracil (5FU), raltitrexed can be administered safely in patients with cardiovascular disease, as well as in patients with dihydropyrimidine dehydrogenase deficit. Since raltitrexed is administered in 15-minutes infusion, complications related to continuous infusion can be avoided, and it becomes a potential good candidate for locoregional treatments as hepatic intra-arterial or intra-peritoneal infusion. Despite these potential benefits over 5FU, clinical trials failed in their temptation to replace the 5FU in colorectal cancer patients, mainly due to raltitrexed toxicity at 3mg/m2 every 3 weeks. Oxaliplatin has demonstrated a synergic effect when combined with TS inhibitors, and its association with raltitrexed was evaluated at 130mg/m2 of oxaliplatin and 3mg/m2 of raltitrexed, every 3 weeks. Actually, one of the first-line standard regimens in metastatic colorectal cancer patients is the biweekly FOLFOX (85mg/m2 of oxaliplatin, and infusional 5FU) plus bevacizumab regimen, since a significant progression-free survival (PFS) benefit was observed over FOLFOX plus placebo. Biweekly administration of raltitrexed at 2mg/m2 demonstrated a favorable toxicity profile even in patients aged \>65 years. Besides, the association of raltitrexed, oxaliplatin and bevacizumab seems safe. Then, the investigators decided to perform a randomized pharmacokinetic comparative study between biweekly TOMOX (raltitrexed 2 mg/m2 and oxaliplatin 85mg/m2) and triweekly TOMOX (raltitrexed 3 mg/m2 and oxaliplatin 130mg/m2) regimens in metastatic colorectal cancer patients, in a "ping-pong" crossover strategy to reduce the intra-individual variability. Bevacizumab was allowed at the dose of 5mg/kg or 7.5mg/kg, in biweekly and triweekly schedules, respectively. The secondary end-points were, objective response rate evaluated by RECIST 1.1 criteria, PFS, overall survival (OS), toxicity, and the comparison of toxicity between two arms for the first 2 cycles. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: TOMOX, DRUG: Bevacizumab Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * performance status (ECOG-PS) of 0 or 1 * patient with histologically proven colorectal cancer with distant metastases * measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * life expectancy > 12 months * signed written informed consent Exclusion Criteria: * prior chemotherapy at metastatic stage * presence of brain or meningeal metastases * other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix and squamous or basal cell carcinoma of the skin * preexisting peripheral neuropathy * known hypersensitivity to any component of the study treatment * any psychiatric condition compromising the understanding of information or conduct of the study * pregnancy, breast-feeding or absence of adequate contraception for fertile patients * patient under guardianship, curator or under the protection of justice

Study Objectives To compare the difference between the ARIMIDEX group and the tamoxifen group in the incidence of abnormal endometrial histological findings arising after treatment has commenced. Conditions: Breast Cancer Intervention / Treatment: DRUG: Anastrozole (Arimidex), DRUG: Tamoxifen (Nolvadex), DRUG: Nolvadex placebo, DRUG: Arimidex placebo Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients eligible for entry into the main ATAC trial (1033IL/0029) * Not received any previous tamoxifen, for whatever reason * Not undergone a hysterectomy and do not have a hysterectomy planned within the next 6 years * No previous endometrial ablation Exclusion Criteria: * Excluded from entry into the main ATAC trial (1033IL/0029). As detailed in Section 4.4 of the main ATAC trial (1033IL/0029)

Study Objectives This phase II trial is studying how well sunitinib works in treating patients with recurrent or persistent leiomyosarcoma of the uterus. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Conditions: Recurrent Uterine Sarcoma, Uterine Leiomyosarcoma Intervention / Treatment: DRUG: sunitinib malate 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: * Histologically confirmed leiomyosarcoma of the uterus * Recurrent or persistent disease * Refractory to curative therapy or established treatments * Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan * Ascites and pleural effusions are not considered measurable disease * Must have >= 1 target lesion to assess response * Tumors in a previously irradiated field are considered non-target lesions unless there is documented progression or biopsy-confirmed persistence >= 90 days after completion of radiotherapy * Received at least 1 but no more than 2 prior cytotoxic regimens * Initial treatment may have included high-dose chemotherapy, consolidation, or extended therapy administered after surgery or nonsurgical assessment * Cytotoxic regimens may have included any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa * Not a candidate for a higher priority GOG protocol * No known brain metastases * GOG performance status 0 <= age <= 2 (for patients who have received 1 prior regimen) OR GOG 0 <= age <= 1 (for patients who have received 2 prior regimens) * Absolute neutrophil count >= 1,500/mm³ * Platelet count >= 100,000/mm³ * Hemoglobin >= 9 g/dL * Creatinine <= 1.5 times upper limit of normal (ULN) * Bilirubin <= 1.5 times ULN * SGOT <= 2.5 times ULN * Alkaline phosphatase <= 1.5 times ULN * QTc < 500 msec * LVEF normal by echocardiogram * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for >= 1 month after completion of study treatment * Patients with a pre-existing thyroid abnormality unable to maintain normal thyroid function with medication are not eligible * No significant EKG abnormalities (i.e., no history of serious ventricular arrhythmia OR EKG with ventricular tachycardia or ventricular fibrillation >= 3 beats in a row) * No sensory or motor neuropathy > grade 1 * No NYHA class III-IV congestive heart failure * NYHA class II cardiac dysfunction allowed * History of NYHA class II heart failure that is asymptomatic on treatment allowed * No active infection requiring antibiotics * No other invasive malignancies within the past 5 years except for nonmelanoma skin cancer * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate * No poorly controlled hypertension (i.e., systolic blood pressure [BP] >= 140 mm Hg or diastolic BP >= 90 mm Hg) * No gastrointestinal tract disease resulting in an inability to take oral medication * No requirement for IV alimentation * No active peptic ulcer disease * No other condition that would impair ability to swallow and retain study drug * No serious or nonhealing wound, ulcer, or bone fracture * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days * No cerebrovascular accident or transient ischemic attack within the past year * No myocardial infarction, cardiac arrhythmia, stable or unstable angina, or symptomatic congestive heart failure within the past year * No pulmonary embolism within the past year * No uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infections * Psychiatric illness or social situations that would preclude study compliance * Recovered from prior surgery, chemotherapy, or radiotherapy * Prior anthracycline exposure and central thoracic radiation that included the heart allowed provided patient has New York Heart Association (NYHA) class II cardiac function * At least 1 week since prior hormonal therapy * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) or radiotherapy * At least 4 weeks since prior major surgery * At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and no recurrent or metastatic disease * At least 3 years since prior adjuvant chemotherapy for localized cancer of the breast and no recurrent or metastatic disease * No prior radiotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma * No prior chemotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma * No prior noncytotoxic chemotherapy for recurrent or persistent disease * No prior surgical procedures affecting absorption * No coronary or peripheral artery bypass graft or stenting within the past year * No other prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or vascular endothelial growth factor [VEGF] Trap) * No other prior cancer treatment that would preclude study treatment * At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following: * Azole fungals (e.g., ketoconazole or itraconazole) * Clarithromycin * Erythromycin * Diltiazem * Verapamil * HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir) * Delavirdine * At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: * Rifampin * Rifabutin * Carbamazepine * Phenobarbital * Phenytoin * Hypericum perforatum (St. John's wort) * Efavirenz * Tipranavir * No concurrent proarrhythmic potential agent, including any of the following: * Terfenadine * Quinidine * Procainamide * Disopyramide * Sotalol * Probucol * Bepridil * Haloperidol * Risperidone * Indapamide * Flecainide * No concurrent therapeutic coumarin-derivative anticoagulants, such as warfarin * Doses <= 2 mg daily allowed for prophylaxis of thrombosis * Low molecular weight heparin allowed provided PT INR <= 1.5 * No concurrent amifostine or other protective agents * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No other concurrent anticancer agents or therapies

Study Objectives The purpose of this study is to evaluate the efficacy of treatment with azacitidine (an FDA approved drug for the treatment of MDS) and high dose ascorbic acid in patients with TET2 mutations. This approach is intended to enhance the enzymatic activity of TET2 protein, which in term may help to improve counts and symptoms, related to Myelodysplastic Syndromes and Acute Myeloid Leukemia. This combination is specific to individuals who carry this mutation. Conditions: Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Acute Myeloid Leukemia Intervention / Treatment: DRUG: Azacitidine, DRUG: Ascorbic acid 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 must have a confirmed heterozygous TET2 mutations identified by next generation targeted deep sequencing. * Patients must have MDS, or MDS/MPN overlap defined by 2016 World Health Organization (WHO) criteria. Both newly diagnosed or previously treated MDS or MDS/MPN patients are eligible as long as the patient has never received prior treatment with azacitidine or decitabine. * Patients with Leukemic/blast phase transformation MPN. * Patient with AML according to 2016 WHO criteria. * Newly diagnosed patients who are ineligible or declined to receive intensive chemotherapy after discussion of risks and benefits of that approach or patients with primary refractory/relapsed AML. * Patients with active central nervous system (CNS) leukemia eligible at the discretion of treating physician. * Relapse/Refractory is defined as at least 1 course of treatment for AML excluding any patients treated with azacitidine or decitabine. * Patients should be off any prior treatment or line of therapy for 2 weeks prior to start study with the exception of hydrea (Hydroxyurea). * Prior therapy with hydroxyurea, biological or targeted therapy (e.g. flt3 inhibitors, other kinase inhibitors) or hematopoietic growth factors is allowed. * Eastern Cooperative Oncology Group (ECOG) performance status <= 3. * Patients must have normal organ and marrow function as defined at the discretion of the treating physician and PI. * Women of childbearing potential must have a negative serum or urine pregnancy test within 10 <= age <= 14 days prior to enrollment. * Patients must have the ability to understand and the willingness to sign a written informed consent document. * Patient must be willing to comply with all aspects of the protocol including completing the drug diary. * Patient must discontinue any and all use of multivitamin and/or vitamin c medication 24 hours before first dose of Ascorbic Acid. Exclusion Criteria: * Any prior treatment with azacitidine or decitabine. * Patients diagnosed with acute promyelocytic leukemia (APL), AML-M3. * Patients receiving other active treatment for their myeloid malignancy including investigational agents with the exception of hydrea for white blood cell control. * Nursing or pregnant women. * History of allergic reactions to either azacitidine or ascorbic acid. * Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with higher risk of bleeding (deemed by the treating physician) or on anticoagulation. * Patients who are unwilling or unable to comply with all study requirements.

Study Objectives 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly referred to as the statins, have proven therapeutic and preventative effects in cardiovascular diseases. Recently, there are emerging interests in their use as anticancer agents based on preclinical evidence of their antiproliferative, proapoptotic, anti-invasive, and radiosensitizing properties. Inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by the statins interferes with the rate-limiting step of the mevalonate pathway, leading to reduced levels of mevalonate and its downstream products, many of which play important roles in critical cellular functions such as membrane integrity, cell signaling, protein synthesis, and cell cycle progression. Perturbations of these processes in neoplastic cells by the statins may therefore result in control of tumor initiation, growth, and metastasis. The statins have demonstrated growth inhibitory activity in cancer cell lines and preclinical tumor models in animals. Simvastatin, a member of the statin family, profoundly impaired basal and growth factor-stimulated SCLC cell growth in vitro and induced apoptosis. SCLC cells treated with simvastatin were sensitized to the effects of the chemotherapeutic agent etoposide. Moreover, SCLC tumour growth in vivo was inhibited by simvastatin. Therefore, the investigators will conduct this phase II trial to evaluate the efficacy \& toxicity of irinotecan/cisplatin plus simvastatin in patients with chemo-naïve ED-SCLC. Conditions: Small Cell Lung Cancer Intervention / Treatment: DRUG: Irinotecan, DRUG: Cisplatin, DRUG: Simvastatin Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic or cytologic diagnosis of SCLC * Extensive-stage disease, defined as disease extending beyond one hemithorax or involving contralateral mediastinal, hilar or supraclavicular lymph nodes, and/or pleural effusion. * No prior chemotherapy, immunotherapy, or radiotherapy * Performance status of 0, 1, 2 on the ECOG criteria. * At least one unidimensional measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST. 2000). * Patient compliance that allow adequate follow-up. * Adequate hematologic (WBC count >= 4,000/mm3, platelet count >= 150,000/mm3), hepatic (bilirubin level <= 1.5 mg/dL, AST/ALT <= 80 IU/L), and renal (creatinine concentration <= 1.5 mg/dL) function. * Informed consent from patient or patient's relative. * Males or females at least 18 years. * If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative HCG test within 7 days prior to the study enrollment. * No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole. * Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs Exclusion Criteria: * Inability to comply with protocol or study procedures. * A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study. * A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV. * Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. * Concurrent administration of any other antitumor therapy. * Pregnant or breast-feeding.

Study Objectives This open-label single arm study will evaluate the efficacy and safety of Avastin added to XELOX or FOLFOX in patients with metastatic colorectal cancer and disease progression on 1st line therapy with FOLFIRI plus Avastin. Patients will receive either Avastin (7.5mg/kg iv infusion every 3 weeks) and standard XELOX (Xeloda \[capecitabine\] plus oxaliplatin) chemotherapy or Avastin (5 mg/kg iv infusion every 2 weeks) and standard FOLFOX (5-FU and leucovorin plus oxaliplatin) chemotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100 individuals. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: fluorouracil (5FU), DRUG: leucovorin, DRUG: bevacizumab [Avastin], DRUG: capecitabine [Xeloda], DRUG: oxaliplatin Location: Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * adult patients >=18 years * metastatic colorectal cancer * at least 1 measurable lesion according to RECIST v. 1.1 * patients with disease progression with prior FOLFIRI + Avastin therapy who are not candidates for primary metastasectomy * disease progression <= 8 weeks after last dose of Avastin * ECOG <=2 * No more than 8 weeks between 1st-line treatment with FOLFIRI + Avastin and 2nd-line treatment with XELOX or FOLFOX + Avastin Exclusion Criteria: * disease progression > 8 weeks after last Avastin administration * clinically significant cardiovascular disease * CNS disease except for treated brain metastasis * history of other malignancies within 2 years prior to start of study treatment (with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix) * major surgery, open biopsy, or significant traumatic injury within 28 days prior to start of study treatment

Study Objectives The purpose of this study is to determine the effectiveness and safety of PROCRIT (Epoetin alfa) at a starting dose of 60,000 Units (U) once every week (QW) to a target hemoglobin (Hb) of 12 g/dL (Initiation Phase), followed by a dose of 80,000 Units once every three weeks (Q3W) to maintain a Hb range of 11.5 to 12.5 g/dL (Maintenance Phase) in cancer patients receiving chemotherapy. Conditions: Cancer, Anemia Intervention / Treatment: DRUG: Epoetin alfa Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed diagnosis of non-myeloid malignancy and receiving chemotherapy * Baseline Hb of <= 11 g/dL * Planned chemotherapy for a minimum of 15 weeks to be administered every 3 weeks * Female patients with reproductive potential must have a negative serum pregnancy test at screening. Exclusion Criteria: * No uncontrolled hypertension or recent history (within 6 months) of uncontrolled cardiac arrhythmias * No pulmonary embolism * or thrombosis * No transfusion of white blood cells or packed red blood cells within 28 days of Epoetin alfa treatment * No prior treatment with Epoetin alfa or any other erythropoetic agent within the previous three months

Study Objectives This study will evaluate the efficacy and safety of treatment with oral capecitabine or intravenous (IV) 5-fluorouracil (5-FU), in combination with epirubicin and cyclophosphamide, prior to surgery in participants with breast cancer. The participants will receive 4 cycles of neoadjuvant Capecitabine + Epirubicin + Cyclophosphamide (CEX) or 5-FU + Epirubicin + Cyclophosphamide (FEC 100) chemotherapy during first treatment period (Period 1, Days 1-85). After 4-6 weeks of the fourth cycle of neoadjuvant chemotherapy (Day 120 +/- 7 days), breast surgery with regional lymph node dissection will be performed, followed within a maximum of 6 weeks by the second treatment period (Period 2, Days 1 to 85) when participants in both study arms will receive 4 cycles of adjuvant docetaxel 100 milligrams per meter square (mg/m\^2) by IV infusion on Day 1 of each 21-day cycle. Upon completion of the second treatment period, participants will enter the post-treatment follow-up period which will last for 5 years from the initial date of participant randomization. During this period participants will be evaluated once a year on the anniversary date of randomization. Conditions: Breast Cancer Intervention / Treatment: DRUG: 5-Fluorouracil, DRUG: Capecitabine, DRUG: Cyclophosphamide, DRUG: Docetaxel, DRUG: Epirubicin Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Females with a unilateral, non-inflammatory, non-multicentric, non-metastatic breast adenocarcinoma, not considered candidates for conservative management, and whose diagnosis had been histologically confirmed as T2 <= age <= 3, N0 <= age <= 1, M0 according to the tumor-nodes-metastasis (TNM) classification * Clinically or radiologically measurable lesion (in 2 dimensions) * Eastern Cooperative Oncology Group (ECOG) performance Status less than equal to (<=) 1 Exclusion Criteria: * Females presenting with brain metastases or a neurological or psychiatric disorder which could interfere with proper treatment compliance * Previous radiotherapy, chemotherapy, or hormonal therapy for breast cancer * Previous history of a malignancy in last 5 years other than cutaneous basal cell carcinoma or carcinoma in situ of the uterine cervix * Serious concomitant infection * Pregnant or lactating females

Study Objectives Immune checkpoint inhibitors(ICIs) combined with angiogenesis inhibitors may is synergistic in elderly patients with advanced non-small cell lung cancer(NSCLC), however its true efficacy is still unclear. The investigators retrospectively compared clinical efficacy and safety of driver-negative elderly patients with advanced NSCLC treated with ICIs with(or without)angiogenesis inhibitors in the Cancer Center of the Affiliated Suzhou Hospital of Nanjing Medical University. Conditions: NSCLC Intervention / Treatment: DRUG: Immune checkpoint inhibitors plus angiogenesis inhibitors, DRUG: Immune checkpoint inhibitors without angiogenesis inhibitors Location: China Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age >=65 years. * Stage IV according to the AJCC Cancer grading manual (8th edition). * Histologically confirmed NSCLC. * No driver mutations. * Received at least 2 courses of immunotherapy. * Expected survival time > 3 months. * No concurrent malignancy. * Not participating in a clinical trial. * The functions of important organs were basically normal. * Sign informed consent.

Study Objectives The aim of this study is the safety and efficacy of cryosurgery plus NK immunotherapy to recurrent pharyngeal cancer. Conditions: Recurrent Pharyngeal Cancer Intervention / Treatment: DEVICE: Cryosurgery, BIOLOGICAL: NK immunotherapy Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * All standard therapies have failed according to NCCN guidelines or the patient refuses standard therapies after cancer recurrence * Body tumor 1 <= age <= 6, the maximum tumor length < 5 cm * KPS >= 70, lifespan > 6 months * Platelet count >= 80×109/L，white blood cell count >= 3×109/L, neutrophil count >= 2×109/L, hemoglobin >= 80 g/L Exclusion Criteria: * Patients with cardiac pacemaker * Patients with brain metastasis * Patients with grade 3 hypertension or diabetic complication, severe cardiac and pulmonary dysfunction

Study Objectives This multi-center, open-label, pharmacokinetic study will evaluate the bioequivalence (BE) or relative bioavailability (rBA) of three new idasanutlin-tablet variants compared to the reference tablet formulation following oral administration of a 300 milligrams (mg) dose in participants with solid tumors for whom no further treatment options are available. Following the four administrations of idasanutlin in the BE/rBA cycle of the study (Cycle 1), participants who have no clinically defined progressive disease and who recover from any prior treatment toxicity to Grade less than or equal to (\</=) 1 may enter the optional treatment extension phase. This extension phase will continue for additional 28-day cycles or until disease progression or unacceptable toxicity is observed. Conditions: Solid Tumors Intervention / Treatment: DRUG: Idasanutlin Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Participant must have histologically or cytologically confirmed advanced malignancies, except all forms of leukemia and lymphoma, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the participant * Measureable or evaluable disease by RECIST v1.1 for solid tumors prior to the administration of study drug * Ability to understand and willingness to sign a written informed consent form and comply with all study requirements * Life expectancy of greater than or equal to (>=)12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * New York Heart Association (NYHA) status of less than or equal to (<=)1 * Women of childbearing potential and men should remain abstinent or agree to use an effective form of contraception and to continue its use for the duration of study treatment and for a period of time after the last dose of study treatment * Adequate bone marrow function, hepatic function, and renal function Exclusion Criteria: * Participants with prostate cancer who are unable to interrupt treatment with ketoconazole; ketoconazole treatment must be discontinued 2 weeks prior to first dose of study medication and is not allowed during Cycle 1, but may be used in the optional extension phase. * Administration of investigational agents or investigational drugs <=4 weeks or less than (<)5 times the terminal half-life prior to study treatment start, whichever is longer * Active gastrointestinal (GI) conditions and uncontrolled irritable bowel disease or pre-existing GI disorders that may interfere with proper absorption of the study drug * History of allergic reactions attributed to components of the formulated product * History of seizure disorders or unstable central nervous system metastases * Presence of any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study * Evidence of electrolyte imbalance * Pregnant or breast feeding * Known coagulopathy, platelet disorder or history of non-drug-induced thrombocytopenia * Current treatment with oral or parenteral anti-coagulants/antiplatelet agents * Acute toxicities from any prior anti-tumor therapy, surgery, or radiotherapy that has not resolved to Grade <=2, except alopecia * Last dose of prior anti-tumor therapy <21 days prior to the first administration of idasanutlin or <5 times terminal half-life of that therapy, whichever is shorter * Refusal to potentially receive blood products and/or have a hypersensitivity to blood products * Known bone marrow disorders which may interfere with bone marrow recovery or participants with delayed recovery from prior chemoradiotherapy * Planned procedure or surgery during the study * History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C * Blood transfusion within 4 weeks prior to screening * History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias * Current treatment with medications that are well known to prolong the QT interval

Study Objectives Background: Patients with the genetic disorder neurofibromatosis Type 1 (NF1) are at increased risk of developing tumors of the central and peripheral nervous system. These include plexiform neurofibromas. The conventional treatment of these internal plexiform neurofibromas is surgery. This surgery can be possible on a single and limited tumor. On the other hand these tumors are often surgically intractable due to their multiplicity and their infiltrating characteristics Increased activity of mammalian target of rapamycin(mTOR) protein is seen in neurofibromas. mTOR inhibitor rapamycin , or its derivatives such as everolimus may slow or stop tumor growth in patients with NF1. Objectives: Primary objectives To determine whether everolimus has an effect on the volume of surgically intractable and life-threatening internal plexiform neurofibromas in patients with neurofibromatosis 1. Secondary objectives To determine whether everolimus has an effect on the number and the volume of cutaneous neurofibromas; to determine whether everolimus modify the signaling pathways in cutaneous neurofibromas. Eligibility: - Adults with neurofibromatosis type 1 with at least one internal plexiform neurofibroma, life-threatening or causing significant morbidity through compression of organs. This or these internal plexiform neurofibroma(s) should be intractable by surgery. Design: An open-label, single arm, non-randomized, single stage phase IIa study. Baseline phase: Baseline evaluations will be performed within 2 weeks, and up to a maximum of 4 weeks for specific exams, before the first dose of study drug. Treatment phase/duration of treatment: All patients will be treated with RAD001 10 mg p.o daily dose for one year except in case of unacceptable toxicity, death, or discontinuation from the study for any other reason. Follow-up phase: All patients will have two follow-up visits scheduled at 18 and 24 months after the first dose of the study drug to follow for adverse events (AEs) and serious adverse events (SAEs) that may have occurred after discontinuation from the study and for internal plexiform neurofibromas assessment. Radiological review: All Magnetic Resonance Imaging (MRIs) obtained at baseline, during the treatment period and the follow-up period will be reviewed by the Neuroradiologist of the study. Conditions: Neurofibromatosis Type 1, Plexiform Neurofibroma, Neurofibromatoses Intervention / Treatment: DRUG: RAD001: Everolimus Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Clinical diagnosis of NF1, according to NIH criteria, with internal plexiform neurofibroma (PN) and at least 1 of criteria for NF1: 6 or more café-au-lait spots Freckling in the axilla or groin Optic glioma 2 or more Lisch nodules Distinctive bony lesion 1-degree relative with NF1 * At least 1 inoperable PN(s) that has/have the potential to cause significant morbidity: Paravertebral lesions that could compromise the spinal cord Head and neck lesions that could compromise the airway or great vessels Brachial or lumbar plexus lesions that could cause nerve compression and loss of function Lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems Lesions of the extremity that cause limb hypertrophy or loss of function Painful lesions * Complete resection of a PN with acceptable morbidity is not feasible OR patient refuses surgery OR the number of PNs leads to not feasible surgery according to the steering committee's site * Measurable PN amenable to volumetric MRI analysis using fusion of images * Measurable lesion (at least 3 cm in one dimension) * Karnofsky >70% * 18<= Age <=60 * absolute neutrophil count (ANC) >=1.5x109/L, Platelets >=100x109/L, Hb >9g/dL * bilirubin: <=1.5xULN, ALT and AST <=2.5xULN unless evident Gilbert disease (amendment n°2). For patients with known liver metastases: AST and ALT <= 5xULN * Creatinine <= 1.5xULN * Life expectancy >= 2 years * Cholesterol <=300 mg/dL or <=7.75 mmol/L and triglycerides <= 2.5x ULN * Women of childbearing potential must have had a negative serum pregnancy test within 7 days and a negative urine pregnancy test within 72 hours prior to the administration of RAD001 start and must use an effective birth control method. * Men should use condoms and their partner(s) use an effective birth control method * A written informed consent obtained Exclusion Criteria: Patients who/with: * have previously received mTOR inhibitors * a known hypersensitivity to RAD001 or other rapamycin or to its excipients * receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent. (Dose equivalent to 10 mg/day of methylprednisone), topical steroids or organotherapy for bilateral adrenalectomy are acceptable * a known history of HIV seropositivity * acute viral hepatitis * autoimmune hepatitis * with an active, bleeding diathesis. Patients may use coumadin or heparin preparations * have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation * have a history of another primary malignancy <=3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix * 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. Oral contraceptives are not acceptable alone * a contraindication to MRI * are using other investigational agents or who had received investigational drugs <= 4 weeks prior to study treatment start * unwilling or unable to comply with the protocol * not affiliated to health system

Study Objectives The purpose of this study is to assess pharmacodynamics and safety of JNJ-212082 in order to select the recommended dose of JNJ-212082 for patients with castration resistant prostate cancer. Conditions: Prostatic Neoplasms Intervention / Treatment: DRUG: JNJ-212082 Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the prostate, but not with neuroendocrine differentiation or of small cell histology * No Prior cytotoxic chemotherapy (including estramustine) for the treatment of prostate cancer * Surgically or medically castrated, with testosterone levels of < 0.5 ng/mL * PSA level of at least 2 ng/ml at Screening * PSA progression according to PCWG2 eligibility criteria or objective progression by RECIST criteria for patients with measurable disease after androgen deprivation Exclusion Criteria: * Surgery or local prostatic intervention within 4 weeks of the first dose. In addition, any clinically relevant sequelae from the surgery have not resolved prior to initial treatment * Radiotherapy, or immunotherapy within 4 weeks, or single fraction of palliative radiotherapy within 2 weeks of administration prior to initial treatment * Known brain metastasis * Uncontrolled hypertension (systolic BP greater than 160 mmHg or diastolic BP greater than 95 mmHg) * Active or symptomatic viral hepatitis or chronic liver disease

Study Objectives THe primary objective is to estimate the response rate at 6 months to Gleevec® in patients with plexiform neurofibromas Conditions: Neurofibromatosis Intervention / Treatment: DRUG: Gleevec 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 3 <= age <= 65 years. * Diagnosis of neurofibromatosis (NF1), as outpatients. * Presence of clinically significant plexiform neurofibromas (biopsy proven if possible with tissue blocks available); that is tumors that are potentially life threatening or are impinging on vital structures or significantly impair the quality of life from pain or other symptoms. * Patients must have measurable disease by magnetic resonance imaging (MRI). Patients must have a Karnofsky or Lansky Performance score of > 80% and a life expectancy of > 2 months. * Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC > 1.5 x 109/L, platelets > 100 x 109/L. * Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. * Written, voluntary informed consent. Exclusion criteria: * Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing. * Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed. * Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study) * Female patients who are pregnant or breast-feeding. * Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection). * Patient has a known brain metastasis. Non-specific CNS changes on MRI/CT characteristic of NF1 are allowed, but not known CNS malignancies. * Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis). * Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. * Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry, unless the disease is rapidly progressing. * Patient previously received radiotherapy to greater than 25 % of the bone marrow * Patient had a major surgery within 2 weeks prior to study entry. * Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Study Objectives The purpose of this study is to determine whether using FOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) prior to surgery in patients with pancreatic cancer is safe and well tolerated. This study will obtain preliminary data on the response of the cancer to this therapy by Magnetic Resonance Imaging (MRI) and by studying the cancer after it is resected surgically. In addition, the investigators will perform biochemical studies on the tumor tissue obtained from your tissue biopsy as well as from the tumor removed by the surgeon in order to measure the effect of treatment with FOLFIRINOX and SBRT on several proteins that may be important in the behavior of pancreatic cancer cells. The data obtained from this trial will be extremely valuable to help improve the approach to treating pancreatic cancer in the future. If you do not undergo surgery after completion of FOLFIRINOX + SBRT, the investigators will request a second biopsy of the tumor under computer tomography (CT) -guidance in order to measure the effect of treatment on your tumor. Conditions: Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms Intervention / Treatment: DRUG: Modified FOLFIRINOX, RADIATION: Stereotactic Body Radiotherapy (SBRT) 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: Patients eligible must have: * Histologic or cytologic diagnosis of pancreatic adenocarcinoma. * Radiographically resectable or borderline resectable disease as reviewed by an experienced surgical oncologist at Emory. * Age >= 21 years. * Not received prior chemotherapy or radiation for pancreatic cancer. * ECOG performance status of 0 <= age <= 1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Adequate bone marrow function: absolute neutrophil count > 1,500/cmm, platelet count > 100,000/cmm. * Understanding and be informed of the investigational nature of this study and must give written informed consent prior to the receiving of treatment per this protocol. Exclusion Criteria: Patients who are not eligible have * Histologies including endocrine tumors or lymphoma of the pancreas. * A tumor which is less than 3 mm from the duodenum as measured by either CT or MRI. * History of central nervous system (CNS) metastases. * Liver dysfunction, including total bilirubin > 1.5 mg/dL; aspartate transaminase (AST) and alanine amino transferase (ALT) > 5 times upper limit of the institutional normal. * Creatinine >= 1.5 mg/dL. * Albumin <= 2.5 g/dL. * International Normalized Ratio (INR) >= 1.5 (in the absence of ongoing treatment with warfarin). * Breast feeding. * Serious active infection. * Serious concurrent systemic disorders incompatible with participating in the study (at the discretion of the investigator). * An active second primary malignancy (except in situ carcinoma of the cervix, or adequately treated basal cell carcinoma of the skin) within less than one year of enrollment into this study. * Clinical evidence of distant metastatic disease.

Study Objectives To monitor the safety profile and efficacy of GIOTRIF® (afatinib dimaleate, q.d) in Korean patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: GIOTRIF 20mg, DRUG: GIOTRIF 40mg, DRUG: GIOTRIF 30mg Location: Korea, Republic of Study Design and Phases Study Type: OBSERVATIONAL

Inclusion criteria: * Patients who have been started on GIOTRIF® in accordance with the approved label in Korea * Age = 19 years at enrolment * Patients who have signed on the data release consent form Exclusion criteria: * Known hypersensitivity to afatinib or any of its excipients * Patients with rare hereditary conditions of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption * Patients for whom GIOTRIF® is contraindicated according to the local label

Study Objectives The purpose of the study is to determine whether CEP-701 given in sequence with induction chemotherapy increases the proportion of patients with relapsed acute myeloid leukemia (AML) who achieve a second complete remission (CR). Conditions: Acute Myeloid Leukemia Intervention / Treatment: DRUG: CEP-701, DRUG: high-dose cytarabine, DRUG: Mitozantrone, Etoposide, Cytarabine (combination Chemotherapy) Location: Spain, Romania, Russian Federation, Australia, New Zealand, Poland, Canada, Ukraine, United States, Sweden, Israel, Germany, Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion criteria: * cytological confirmation of AML; * relapsed disease following first CR of 1 month(30days)to 24 months(730days). The time from first relapse to study entry (start of first course of induction chemotherapy) must be no longer than 30days; * confirmation of FLT-3 activating mutation positive status after point of initial relapse; * aged >= 18 years; * written informed consent; * ability to understand and comply with study restrictions; * no comorbid conditions that would limit life expectancy to less than 3 months; * ECOG Performance Score of 0, 1,or 2; * women must be neither pregnant nor lactating, and either of non-childbearing potential or using adequate contraception with a negative pregnancy test at study entry Exclusion criteria: * bilirubin > 2x ULN; * ALT/AST > 3x ULN; * serum creatinine > 1.5 mg/dL; * resting ejection fraction of left ventricle l < 45%(applies only to patients scheduled to receive mitoxantrone, etoposide, and cytarabine [MEC]; * untreated or progressive infection; * any physical or psychiatric cdtn that may compromise participation in the study; * known CNS involvement with AML; * any previous treatment with a FLT-3 inhibitor; * requires current treatment for HIV with protease inhibitors; * active GI ulceration or bleeding; * use of an investigational drug that is not expected to be cleared by the start of CEP-701 treatment

Study Objectives The objective of this study is to evaluate the efficacy and safety of imiquimod cream versus placebo cream when used after cryosurgery in the treatment of actinic keratoses (AKs). Conditions: Actinic Keratosis Intervention / Treatment: DRUG: imiquimod cream, DRUG: placebo cream Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * In good general health * Negative urine pregnancy test (for women of child-bearing potential) and agree to use an approved method of birth control while enrolled in the study. * Prior to cryosurgery, have >= 10 clinically typical (visible or palpable) AKs in an area that exceeds 25 cm2 on the face. * Must have had cryosurgery on 5 to 14 AKs on the face after giving informed consent and prior to receiving study medication. Lesions previously treated with cryosurgery must be healed sufficiently prior to randomization to study cream. * Following cryosurgery, have >= 5 clinically typical (visible or palpable) AKs in an area that exceeds 25 cm2 on the face that are suitable for treatment with the study cream. Exclusion Criteria: * Women who are pregnant, lactating, or planning to become pregnant during the study * Had a medical event within 90 days of the visit (e.g., stroke, heart attack, etc.). * Have any skin condition in the treatment area that may be made worse by treatment with imiquimod (e.g., rosacea, psoriasis, atopic dermatitis, eczema). * Have received specific treatments/medications in the treatment area within the designated time period prior to study treatment initiation

Study Objectives Vaccines made from peptides that are found on leukemia cells may make the body build an immune response and kill cancer cells. Combining vaccine therapy with the immune adjuvant Montanide ISA-51 may be a more effective treatment for chronic myeloid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. This phase I/II trial is studying the side effects and best dose of vaccine therapy when given with Montanide ISA-51 and to see how well they work in treating patients with chronic myeloid leukemia, acute myeloid leukemia, or myelodysplastic syndrome Conditions: Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Myeloid Leukemia in Remission, Chronic Phase Chronic Myelogenous Leukemia, Previously Treated Myelodysplastic Syndromes, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Relapsing Chronic Myelogenous Leukemia Intervention / Treatment: BIOLOGICAL: PR1 leukemia peptide vaccine, DRUG: Montanide ISA 51 VG, BIOLOGICAL: sargramostim, OTHER: laboratory biomarker analysis 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: * Patients must be HLA-A2 positive at one allele * Patients with CML in chronic phase or early accelerated phase, who are not eligible for BMT or interferon, or have failed standard therapy, or have relapsed after BMT * Patients with MDS (FAB subtypes RAEB, and RAEBt) or AML in second or subsequent remission, or AML with a smoldering presentation and who are not candidates for chemotherapy, and who are believed to have a life expectancy of at least 9 weeks * ECOG performance status < 3 * Life expectancy is not severely limited by concomitant illness * Serum bilirubin < 3 mg/dl * Serum creatinine < 2 mg/dl * ALT < 3 x the upper limit of normal * No serologic antibody against proteinase 3 * No known history of Wegener's granulomatosis or other vasculitis * FEV, FVC, and DLCO > 50% of predicted, and no symptomatic pulmonary disease * Not pregnant; all female patients will have a serum pregnancy test, and only those that test negative will be allowed on study * HIV negative * No known allergic reaction to Montanide ISA 51 or Montanide ISA 51 VG adjuvant * No active uncontrolled infection * Patient or representative able to understand the study and consent * Patient is not receiving steroids, cyclosporine, or FK-506 for at least 1 month prior to study entry and during study period * No concomitant use of interferon or chemotherapy during study period other than hydroxyurea to control cell counts * Patients who relapsed within one year of completing the initial vaccination could be retreated with up to 6 additional vaccinations if they remain eligible for treatment according to the original criteria

Study Objectives This 2 arm study will assess the efficacy and safety of intermittent oral Xeloda, or iv fluorouracil/leucovorin, in combination with intravenous Eloxatin (oxaliplatin) in patients previously treated for metastatic colorectal cancer. Patients will be randomized to receive either 1)XELOX (Xeloda 1000mg/m2 po bid on days 1-15 + oxaliplatin) in 3 week cycles or 2) FOLFOX-4 (oxaliplatin + leucovorin + 5-FU in 2 week cycles. The anticipated time on study treatment is until disease progression, and the target sample size is 500+ individuals. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: 5 FU, DRUG: Leucovorin, DRUG: Oxaliplatin, DRUG: Oxaliplatin, DRUG: capecitabine [Xeloda] Location: Spain, Taiwan, South Africa, Poland, United States, Belgium, France, Croatia, Finland, United Kingdom, Canada, Slovakia, Slovenia, Puerto Rico, Serbia, Korea, Republic of, Greece, Israel, Germany, Italy 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; * metastatic colorectal cancer; * >=1 target lesion; * failed first-line chemotherapy with 5-fluorouracil and irinotecan. Exclusion Criteria: * previous treatment with oxaliplatin; * progressive or recurrent disease during or within 6 months of completion of first-line chemotherapy; * >=1 previous chemotherapeutic agent or systemic anticancer regimen for metastatic disease.

Study Objectives Stage IIIA non-small cell lung cancers comprising a mediastinal ganglionic invasion N2 account for 20 to 30% of the NSCLCs. They are almost always potentially resectable, but the results obtained by surgery alone or surgery followed by chemotherapy (CT) and/or radiotherapy (RT) are insufficient. The neoadjuvant approach was tested, in randomized tests of exclusive CT, or in noncomparative tests of RT-CT. Conditions: Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Cisplatin-Gemzar, DRUG: Cisplatin-Navelbine-Radiotherapy, DRUG: Carboplatin-Taxol-Radiotherapy Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Operable and resectable stage IIIA (T1 <= age <= 3, N2) NSCLC * World Health Organization (WHO) performance status of 1 or less Exclusion Criteria: * Severe cardiac, respiratory, renal or hepatic failure

Study Objectives This is a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy and safety of rechallenge chemotherapy in the third or later-line treatment in patients with advanced colorectal cancer. The primary end point is progression free survival (PFS). A total of 42 patients who failed with oxaliplatin, irinotecan and fluorouracil in previous treatment and could not receive the target therapy presently are planned for recruitment. For patients with metastatic colorectal cancer who met admission criteria, oxaliplatin- or irinotecan-based chemo regimen could be used and evaluation was repeated every 6 weeks. The treatment continues until the disease progression or the untolerable adverse reaction. Conditions: Metastatic Colorectal Cancer, Chemotherapy Effect Intervention / Treatment: DRUG: the rechallenge regimen 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 * Patients age between 18 and 80 years * Histologically confirmed metastatic colorectal cancer (mCRC) * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Treatment failure to at least two lines of chemotherapy (regimens should include oxaliplatin, fluorouracil and irinotecan); progression free survival (PFS) of prior oxaliplatin or irinotecan-based chemotherapy should be at least four months without any unrecoverable toxicity. Prior target therapy was acceptable * For those who received other anti-tumor treatment, the toxicity should have been restored, with the time interval from last dose of cytotoxic drugs, radiation or surgery (the wound should be healed completely) >=3 weeks * Life expectancy>=12 weeks * At least one measurable lesion as defined by RECIST 1.1 * Acceptable hematologic, hepatic, and renal function within 7 days from screening: the blood ANC count>=1.5*10^9/L; hemoglobin>=9.0 g/dl, the blood platelet count>=80 x 10^9/L, total bilirubin<1.5*upper limits of normal(ULN), ALT and AST<2.5*ULN(< 5 *ULN for patients with live metastasis), endogenous creatinine clearance rate>50ml/min * Targeted drugs are currently not suitable or affordable Exclusion Criteria * Receiving other systemic anti-cancer treatment within 3 weeks * Prior radiation therapy of target measurable lesion * Presence of Grade III or IV chemo-related toxicity in previous treatment without recovery to Grade II or less * With other malignant tumor in 5 years; except for cured cervical carcinoma in situ or basal cell carcinoma * Symptomatic intracranial or meningeal metastasis * History of uncontrolled seizures, central nervous system dysfunction or mental disorder * Uncontrolled pleural or peritoneal effusion * Severe life-threatening concomitant disease that might impair the safety of patients or affect the completion of treatment, according to the researcher's judgment

Study Objectives The investigators will look for the presence of the fusion gene in all patients operated on for glioma. This search will be limited to all gliomas that show no IDH1 mutation, the latter being sought in both routine and anomalies never co-existing. The hypothesis is that the rate of progression-free survival in grade IV gliomas and III without IDH1 mutation, with the usual chemotherapy, only 15% at 6 months (ie, 85% of patients relapse before 6 months of treatment), must be with this new treatment 35% (primary endpoint). The main objective is the evaluation of disease-free survival at 6 months. Conditions: Recurrent IDHwt Gliomas With FGFR3-TACC3 Fusion, Recurrent IDHwt Gliomas With FGFR1-TACC1 Fusion Intervention / Treatment: DRUG: AZD4547 Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Recurrent glioma after standard treatment, expressing the FGFR3-TACC3 or FGFR1-TACC1 fusion gene as confirmed by RT-PCR sequencing. * First recurrence occurring more than three months from the end of the radiotherapy or occurring outside the irradiated volume. * World Health Organisation performance status 0 <= age <= 2 (KPS>50) with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks. * Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses. If a patient declines to participate in any voluntary exploratory research component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study * Aged at least 18 years. * Patients should be using adequate contraceptive measures which should be maintained during the whole duration of AZD4547 treatment and at least 7 days after treatment suspension. Females should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation Exclusion criteria: * Treatment with any of the following: * Nitrosourea within 6 weeks before the first dose of study treatment * Any investigational agents or study drugs from a previous clinical study within 30 days before the first dose of study treatment * Any other chemotherapy, anticancer immunotherapy or anticancer agents within 4 weeks before the first dose of study treatment, except hormonal therapy. * Potent inhibitors or inducers of CYP3A4 or 2D6 or substrates of CYP3A4 within the required washout period as specified in the section 7.3 * Prior treatment in this or another AZD4547 study, or prior randomisation in a study in which AZD4547 is/was under investigation. Prior treatment with any FGFR inhibitor. * Major surgery (excluding placement of vascular access) within 14 days before the first dose of study treatment * With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment * As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required * Any of the following cardiac criteria: * Mean QT interval corrected for heart rate (QTc) >=470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correction.Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years or any concomitant medication known to prolong the QT interval * History of myocardial infarction, unstable angina, stroke or transient ischemic attack within the last 6 months * Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: * Absolute neutrophile count <1.5 x 109/L * Platelet count <100 x 109/L * Haemoglobin <90 g/L * Alanine aminotransferase >2.5 times the upper limit of normal (ULN) * Aspartate aminotransferase >2.5 times ULN Total bilirubin >1.5 times ULN * Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN * Corrected calcium >ULN * Phosphate >ULN * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD4547 * History of hypersensitivity to active or inactive excipients of AZD4547 or drugs with a similar chemical structure or class to AZD4547 * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements * Any of the following ophthalmological criteria: * Current evidence or previous history of retinal pigmented epithelium detachment (RPED) * Previous laser treatment or intra-ocular injection for treatment of macular degeneration * Current evidence or previous history of dry or wet age-related macular degeneration * Current evidence or previous history of retinal vein occlusion (RVO) * Current evidence or previous history of retinal degenerative diseases (eg, hereditary) * Current evidence or previous history of any other clinically relevant chorioretinal defect * Contraindications to MRI

Study Objectives Evaluation of the potential perpetrator effect of BAY1841788 (ODM-201) on rosuvastatin pharmacokinetics. PK of BAY1841788 (ODM-201) after single and repeated administration in male and female subjects. Conditions: Healthy Volunteers, Pharmacokinetics, Drug Interaction Intervention / Treatment: DRUG: Rosuvastatin, DRUG: BAY1841788 (ODM-201) Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Healthy subject - as determined by medical history, physical examination and all procedures required by this protocol. * Age: 45 <= age <= 65 at the screening visit. * Race: White. * Body mass index (BMI): >=18.0 and <=29.9 kg/m*2. * Adequate venous access (frequent blood sampling). * Ability to understand and follow study-related instructions. * Females have to be in postmenopausal state, revealed by: Medical history, if applicable (natural menopause at least 12 months prior to first study drug administration; or surgical menopause by bilateral ovariectomy at least 3 months prior to first study drugadministration) and follicle stimulating hormone (FSH) >40 IU/L at screening examination. * Male subjects must agree to use condoms as an effective contraception barrier method during the whole study (starting after informed consent) and for 3 months after the end of treatment with BAY1841788 (ODM-201). In addition, participants must agree to utilize a second reliable method of contraception simultaneously. The second method which has to be used by a female partner of childbearing potential can be one of the following methods: diaphragm or cervical cap with spermicide or intra-uterine device or hormone-based contraception. Exclusion Criteria: * Medical and surgical history * Subjects with clinically relevant findings in medical history e.g. history or currently existing relevant diseases of vital organs, central nervous system (for example seizures) or other organs (e.g. diabetes mellitus). * Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal. * Febrile illness within 1 week before the first study drug administration. * A medical history of risk factors for Torsades de Pointes (e.g. family history of Long QT interval in electrocardiogram Syndrome) or other arrhythmias. * History of myopathia after treatment with statins. * History of rhabdomyolysis or myopathia. * Medical history of any type of psychiatric disorder, especially mood disorders including medical history with suicidal ideation and/or suicide attempts. * History of thyroid disorders, especially hypothyreosis. * History of respiratory disorder (excluding history of bronchitis or pneumonia). * History of myasthenia. * History of muscle pain or muscle ache, muscle soreness of unknown origin or on frequent occasions although an origin might have been found. * History of any clinically significant hypoglycemia or hyperglycemia. * Relevant hepatic disorders like a history of viral hepatitis, cholestasis, disturbances of bilirubin metabolism, any progressive liver disease. * Relevant renal disorders like recurrent glomerulonephritis, renal injury, and renal insufficiency. However, a history of a single episode of uncomplicated nephrolithiasis will not prevent participation.

Study Objectives Patients with metastatic breast cancer considered HER2 negative are screened for HER2-amplified circulating tumor cells. If at least HER2-amplified circulating tumor cell is detected, patients are treated by Trastuzumab - Emtansine (T-DM1) in a single arm phase II with an adaptive design. Conditions: Metastatic Breast Cancer, HER2 Negative Primary Tumor Intervention / Treatment: DRUG: Trastuzumab - Emtansine Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Inclusion criteria for screening: * Breast adenocarcinoma considered HER2-negative on the primary tumour or unknown status HER2 * A least one metastatic site and/or inoperable loco-regional relapse * Measurable disease (RECIST v1.1) * Age from 18 <= age <= 75 * Performance status of 0 <= age <= 2 * Efficient contraceptive in non-menopause women Inclusion criteria for treatment : * At least 1 (Cohort " L ") or 3 (cohort " H ") HER2 amplified CTC * Performance status of 0 <= age <= 2 * Adequate cardiac function * Adequate hematological and biochemical blood tests Exclusion Criteria: * Life expectancy of less than 3 months * Previous history of any other stage III or IV invasive cancer * Male breast cancer * Uncontrolled brain metastases * Significant cumulated exposure to anthracyclines * Current or previous significant history of cardio-vascular/pulmonary disease * Previous use of trastuzumab

Study Objectives The purpose of this study is to evaluate the tolerability of oral azacitidine in the treatment of patients with Myelodysplastic Syndromes (MDS). Conditions: Myelodysplastic Syndromes Intervention / Treatment: DRUG: Oral azacitidine Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Patients must satisfy the following criteria to be enrolled in the study: * Have a documented diagnosis of myelodysplastic syndromes (MDS) according to World Health Organization (WHO) 2008 classification * Age >= 20 years; * Written informed consent; * Eastern Cooperative Oncology Group (ECOG) performance status of 0 <= age <= 2; * Resolution of any toxic effects of prior anti-cancer therapy; and * Negative urine or serum pregnancy test on females of childbearing potential. Exclusion Criteria: The presence of any of the following will exclude a patient from enrollment: * Treatment with chemotherapy, radiotherapy, or surgery within 4 weeks of study registration; * Pregnant or breast-feeding females; * Previous or concomitant malignancy other than MDS; * Significant active cardiac disease within the previous 6 months; * Uncontrolled systemic infection or * Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

Study Objectives The purpose of this study is to find the safest and most effective dose of the drugs bevacizumab and everolimus given in combination for the treatment of metastatic colorectal cancer. Bevacizumab (also called Avastin™) is a drug that is given intravenously (through a vein). Everolimus (also called RAD001) is a tablet that is taken by mouth. Bevacizumab is a protein that is thought to prevent the formation of blood vessels tumors need to grow. RAD001 has multiple capabilities, like bevacizumab it may prevent the formation of blood vessels needed by tumors and it also may stop tumor growth. This study will try to find the safest dose of these drugs that can be tolerated when taken in combination. The study will look at how the drugs work in the body, and will see if there is any effect on metastatic colorectal cancer. Conditions: Colorectal Adenocarcinoma Intervention / Treatment: DRUG: Bevacizumab, DRUG: Everolimus Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have histologically confirmed adenocarcinoma of the colon or rectum that has progressed on, or patient could not tolerate, fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab and/or panitumumab chemotherapy. Disease must be measurable or evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria * Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Patients must not have had major surgery within the 28 days prior to study day 1 or minor surgical procedures within the 7 days prior to study day 1. * Age >18 years. * Karnofsky performance status > 70 percent * Life expectancy of at least 3 months. * Patients must have normal organ and marrow function as defined in the protocol * The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto- toxic. 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 she or her partner are participating in this study, she should inform her treating physician and study PI immediately. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Patients who are pregnant and/or lactating are excluded from this study. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study. * Patients who have received any other investigational agents within the 28 days prior to day 1 of the study. * Patients with known central nervous system (CNS) metastases. * Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg). Initiation of antihypertensive is permitted provided adequate control is documented over at least 1 week before starting treatment. * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device, within 7 days prior to expected start of treatment. * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Serious, non-healing wound, ulcer, or bone fracture * Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio greater than or equal to 1.0 at screening * Any prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix G) * History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment * History of stroke or transient ischemic attack within 6 months prior to study enrollment * History of intolerance or hypersensitivity to prior treatment with bevacizumab or RAD001. * Chronic treatment with systemic steroids or another immunosuppressive agent, though steroids may be used on an as-needed basis - ie - for treatment of nausea. Treatment with megace or low dose glucocorticoids is permitted for treatment of anorexia. * Other concurrent severe and/or uncontrolled medical disease which could compromise safety of treatment as so judged by treating physician * A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection) * Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except coumadin). No history of active GI bleeding or other major bleeding within previous 6 months. * Patients unwilling to or unable to comply with the protocol * Medical need for the continuous administration of any drugs which affect Cytochrome P450, family 3, subfamily A (CYP3A), though the use of low dose glucocorticoids for anorexia and /or nausea is permitted. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results. * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan.

Study Objectives The main purpose of REVLIMID® DUE (Drug Use Examination) is to collect and evaluate the safety information of Korean Multiple Myeloma patients treated with REVLIMID® according to the approved package insert, after approval of marketing authorization for new drug in Korea. In addition, the efficacy information of REVLIMID® in clinical practice is collected and evaluated. This DUE is a multi-centre, observational and non-interventional post-marketing surveillance. The patients can be recruited through both Drug Use Examination after the initiation of Post Marketing Surveillance(contract with institution) and Patient Access Program(PAP) that was performed before REVLIMID® reimbursement. Total 624 patient has enrolled in PMS by 07Sep2016. Validation process for eligibility for safety assessment has been conducted by site monitoring process by 07Dec2016. REVLIMID® DUE is to investigate frequency and change of Adverse Events(AEs) /Adverse Drug Reactions(ADRs), Serious Adverse Events(SAEs)/Serious Adverse Drug Reactions(SADRs), unexpected AE/ADR and unexpected SAE/SADR, and to scrutinize factors influencing safety \& efficacy of the drug. It is necessary to examine patients' demographics and baseline characteristics, medical history, status of REVLIMID® treatment, concomitant medication and evaluation of safety and final efficacy (best response) assessment. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: REVLIMID®, DRUG: Dexamethasone Location: Korea, Republic of Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Korean male or female who are diagnosed with Multiple Myeloma * In-patients or out patients during the REVLIMID® Drug Use Examination period who are intended to be treated with REVLIMID ® * Patients who are registered for Risk Management Program of Celgene Exclusion Criteria: * There's no exclusion criteria

Study Objectives The goal of this clinical research study is to learn if minocycline can reduce the symptoms reported by patients with oropharynx cancer, nasopharynx cancer, or unknown primary cancer of head and neck, who receive treatment with radiation therapy. Conditions: Oropharynx Cancer Intervention / Treatment: DRUG: Minocycline, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: DOUBLE

Inclusion Criteria: * Patients with a pathologically proven diagnosis of oropharyngeal cancer, nasopharyngeal cancer, or unknown primary cancer of head and neck in MDACC receiving radiation therapy with or without induction chemotherapy. * Patients > = 18 years. * Patients with the above cancers, T0, TX, T1 to T3, N any, M0 receiving IMRT (to unilateral or bilateral neck) at least 64 <= age <= 72 Gy in 6 <= age <= 7 weeks as definitive treatment. * Patients must have normal renal function test and no prior renal disease: The screening cut off for serum creatinine < upper limit of normal. * Patients must have normal hepatic function test and no prior liver disease: The screening results for total bilirubin must be < 1.5 times the upper limit of normal. The screening results for the following must be < 2 times the upper limit of normal for patients to be eligible: Alkaline phosphatase (ALP) and Alanine aminotransferase (ALT). The screening results for Aspartate aminotransferase (AST) must be < 2 times the upper limit of normal if available. * Patients who speak English (due to the novel research and its complexity, we are only accruing English speaking patients to the protocol). * Patients must be willing to discontinue taking dong quai and/or St John's wort. * Patients must be willing and able to review, understand, and provide written consent. Exclusion Criteria: * Patients receiving concurrent chemotherapy or concurrent biologic agent. * Patients who are taking medications or have conditions that potentially preclude use of any study medications or interventions as determined by the treating physician. * Patients who are enrolled in another symptom management trial or receiving active treatment under another clinical trial. * Bile duct obstruction or cholelithiasis. * History of clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies or drug reaction. * Pre-existing psychosis or bipolar disorder. * Hypersensitivity to any tetracyclines. * Patients on anticoagulants (ie warfarin/heparin). * Patients with INR > 1.5. * Patients taking any tetracycline within the last 15 days. * Patients that are pregnant. * Patients treated with upfront radical surgery at the primary site (other than diagnostic tonsillectomy or excision).

Study Objectives The goal of this clinical research study is to find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Researchers also want to find out if combining busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine will improve the treatment, compared with the previous standard method using busulfan and fludarabine alone. Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndrome, Chronic Myeloid Leukemia Intervention / Treatment: DRUG: Clofarabine, DRUG: Busulfan, DRUG: Fludarabine, OTHER: Stem Cell Infusion, DRUG: Thymoglobulin (ATG), DRUG: Filgrastim Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score (IPSS scores) (16), and having failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome positive and having failed / being resistant to therapy based on Gleevec or other tyrosine kinase inhibitors. * Patient has not been administered intensive systemic chemotherapeutic drugs within 21 days prior to trial enrollment (bone marrow transplant (BMT) Day -9). Gleevec, alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at least one week prior to admission for this treatment. * No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is resolved on appropriate antibiotics therapy. * age <= 60 * A related or unrelated donor who is HLA-matched or mismatched in 1 HLA, A, B, C, DR or DQ locus is acceptable (i.e. at least a 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current standard for the BMT program). * ZUBROD performance status <2 * Life expectancy is not severely limited by concomitant illness. * Left ventricular ejection fraction >=45% No uncontrolled arrhythmias or symptomatic cardiac disease. * Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) >= 50% of expected corrected for hemoglobin. In patients <= 7 years pulmonary function will be assessed per pediatric BMT routine * Serum creatinine <= 1.5 mg%. * Serum glutamic pyruvic transaminase (SGPT) <= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and perform liver biopsy pror to determining study eligibility. * Female patient is not pregnant (negative human chorionic gonadotropin (hCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine). * Patient or patient's legal representative, parent(s) or guardian able to sign informed consent. Exclusion Criteria: * Effusion or ascites estimated to be >1L prior to drainage. * HIV-positive. * Hepatitis C or HBsAg positive * Prior stem cell transplant after a myeloablative conditioning program (such as busulfan-based using a total dose of >= 12 mg/kg given by mouth or >= 10 mg/kg IV, or a total-body irradiation-based program. * Active or prior Central Nervous System (CNS) leukemia * Biphenotypic acute leukemia.

Study Objectives To confirm the efficacy of CPX-351 compared to 7+3 as first line therapy in elderly patients (60-75 yrs) with high risk (secondary) Acute Myeloid Leukemia. The primary efficacy endpoint will be overall survival. Conditions: High Risk Acute Myeloid Leukemia Intervention / Treatment: DRUG: CPX-351, DRUG: 7+3 (cytarabine and daunorubicin) Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Ability to understand and voluntarily give informed consent * Age 60 <= age <= 75 years at the time of diagnosis of AML * Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow) * Confirmation of: * Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease * AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS * AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL * De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO. * Eastern Cooperative Oncology Group (ECOG) performance status 0 <= age <= 2 * Able to adhere to the study visit schedule and other protocol requirements * Laboratory values fulfilling the following: * Serum creatinine < 2.0 mg/dL * Serum total bilirubin < 2.0 mg/dL, patients with Gilbert's Syndrome should contact the medical monitor * Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN Note: If elevated liver enzymes, above the ULN, are related to disease; contact medical monitor to discuss. * Cardiac ejection fraction >= 50% by echocardiography or MUGA * Patients with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible. Exclusion Criteria: * Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible. * Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization. * Clinical evidence of active CNS leukemia * Patients with active (uncontrolled, metastatic) second malignancies are excluded. * Prior treatment intended for induction therapy of AML; only hydroxyurea is permitted for control of blood counts. For example, a patient with MDS that changes HMA dose and schedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabine alone (>1g/m2/day) or cytarabine plus an anthracycline as well as prior HSCT are also excluded. * Administration of any therapy for MDS (conventional or investigational) must be completed by 2 weeks prior to of the first dose of study drug; in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment. Toxicities associated with prior MDS therapy must have recovered to grade 1 or less prior to start of treatment. * Any major surgery or radiation therapy within four weeks. * Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent). * Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent * Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging) * Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for >=72 hrs. * Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values) * Hypersensitivity to cytarabine, daunorubicin or liposomal products * History of Wilson's disease or other copper-metabolism disorder

Study Objectives Trastuzumab for injection is a biosimilar of Herceptin ® produced by Chia Tai Tianqing Biotechnology Co., LTD, which is a humanized IgG1 monoclonal antibody produced by chinese hamster ovary (CHO) cells. A randomized, double-blind, single-dose, parallel phase I study comparing trastuzumab for injection with Herceptin ® in healthy male volunteers was conducted to evaluate the similarities in pharmacokinetics, tolerability, safety and immunogenicity of Trastuzumab for injection and Herceptin®. Conditions: Metastatic Breast Cancer, Metastatic Gastric Cancer Intervention / Treatment: DRUG: Trastuzumab for injection, DRUG: Herceptin Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Fully understand the purpose of the trial, and have a basic understanding of the pharmacological effects and possible adverse reactions of the drug under study; Voluntary written informed consent in accordance with the Helsinki Declaration; * Healthy male subjects aged >= 18 years and <= 65 years; * Body weight >= 50 kg <= 90 kg, body mass index >= 18 <= 28kg/m2; * The system examination indicators were within the normal range, or the examination results were abnormal but the researchers judged that there was no clinical significance; * Subjects agree to use reliable contraceptive methods for both themselves and their partners during the study period and for 6 months after the study drug infusion. Exclusion Criteria: * History of hypertension or abnormal blood pressure at screening/baseline measurement; * A history of albuminuria or albuminuria as assessed by the investigator as clinically significant; * Received any antibody or protein targeting Vascular Endothelial Cell Growth Factor (VEGF) or VEGF receptors in the previous 1 year; * Study the use of any biological product or live virus vaccine within 3 months prior to drug infusion, or the use of any monoclonal antibody within 12 months; * Have an inherited tendency to bleed or have coagulation dysfunction, or have a history of thrombosis or bleeding; * History of digestive tract perforation or digestive tract fistula; * Unhealed wound ulcers or fractures, or major surgery within 2 months prior to randomization or expected to be performed during the study period or within 2 months after study completion; * Use of a prescription or over-the-counter drug or nutritional supplement within the 5 half-life of the drug or nutritional supplement or within 2 weeks prior to the study drug use; * Positive virology test; * Known allergy to trastuzumab; * Known history of allergic diseases or allergic constitution; * Study the history of blood donation 3 months before drug infusion; * Received any other investigational drug therapy or participated in another interventional clinical trial within 2 months prior to screening * A history of alcohol or drug abuse in the 12 months prior to screening; * A history of mental illness; * Subjects whose spouses plan to become pregnant; * The study cannot be completed according to protocol requirements during the study period; * Conditions considered unsuitable for inclusion by other researchers.

Study Objectives This is a clinical research study of a new investigational treatment for cancer called "DTI-015" to be given by intratumoral injection. Intratumoral injection is when drug is injected directly into the tumor. This study will help doctors find out what is the best dose level for DTI-015 and if this treatment can shrink tumors without causing severe side effects. The effects of the drug on the patient's quality of life (how the patient feels and what the patient can do) and their mental functions (reasoning and thinking abilities) will also be studied. Conditions: Glioma, Brain Neoplasms Intervention / Treatment: DRUG: DTI-015 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: * Histologic proof of recurrent previously irradiated supratentorial malignant gliomas including anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, or anaplastic ependymoma. * It must be judged that gross total resection of the patient's tumor is not possible or the patient must refuse open resection of tumor. The decision that the tumor cannot be totally resected will be made by and mutually agreed upon by the physician investigators in the study. * There must be a tumor volume of each tumor component greater than or equal to 0.5 and less than or equal to 15 cubic centimeters. * The patient must be undergoing a stereotactic biopsy for other clinical reasons than the injection of DTI-015. * The patient must have a Karnofsky functional status rating greater than or equal to 60. * The patient must be fully recovered from the acute effects of any prior chemotherapy or radiotherapy. * The patient must be able to read and fully understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital. * The patient must be willing and able to comply with the protocol. * For a female patient of childbearing potential, the patient must not be pregnant as evidenced by a menses in the last 8 weeks or by a negative urine HCG pregnancy test. Exclusion Criteria: * Any radiotherapy or chemotherapy during four weeks prior to entering the study. * Nitrosoureas or mitomycin C during six weeks prior to entering the study. * Patients with active uncontrolled infection. * Serious liver or bone marrow disorder - specifically serum bilirubin >2.0 mg%, SGOT >2.5 times normal, SGPT >2.5 times normal, absolute neutrophil count <1500/mm3, platelet count <100,000/mm3. * Evidence of renal failure (blood creatinine >2.0 mg%, BUN >30 mg/dl or creatinine clearance >40 ml/min * Evidence of a bleeding diathesis or use of anticoagulant medications. * Unstable or severe intercurrent medical conditions. * For females: risk of pregnancy (i.e., unwillingness to use adequate protection to prevent pregnancy), breast feeding a baby during the study period, or lactation. * Tumors shaped into 3 or more components are excluded. Ovoid-shaped or spherical tumors are allowed. Central necrosis and/or central cystic areas are allowed as long as there is an enhancing rim with a thickness >5 mm. * Patients who have undergone a partial resection of tumor and who have a cavity inside the residual tumor are excluded. * Patients with tumors located in the following areas of the brain will be excluded: brainstem (pons or medulla), midbrain (mesencephalon), primary sensorimotor cortex in the dominant hemisphere, or within 1.5 cm of the optic chiasm, either optic nerve, or any other cranial nerve. * Patients with tumors extending into the ventricular system will also be excluded.

Study Objectives The main objective of the trial is to document the safety of the combination (escalation doses of NGR-hTNF, from 0.2 mcg/sqm to 1.6 mcg/sqm , with a fixed dose of cisplatin, 80 mg/sqm). Safety will be established by clinical and laboratory assessment according to National Cancer Institute Common Toxicity Criteria (NCI-CTC ). Conditions: Solid Tumors Intervention / Treatment: DRUG: NGR-hTNF, DRUG: Cisplatin Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients >=18 years with advanced or metastatic solid tumor not amenable to any clinical improvement by current standard treatments and suitable for a treatment with cisplatin * Life expectancy more than 3 months * ECOG Performance status 0 <= age <= 1 * Absence of any conditions in which hypervolemia and its consequences (e.g. increased stroke volume, elevated blood pressure) may represent a risk for the patient * Adequate baseline bone marrow, hepatic and renal function, defined as follows: * Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L * Bilirubin < 1.5 x ULN * AST and/or ALT < 2.5 x ULN in absence of liver metastasis * AST and/or ALT < 5 x ULN in presence of liver metastasis * Serum creatinine < 1.5 x ULN * Creatinine clearance (estimated according to Cockcroft-Gault formula) >= 50 ml/min * Patients may have had prior therapy providing the following conditions are met: * Chemotherapy, radiation therapy, hormonal therapy or immunotherapy: wash-out period of 28 days * Corticosteroid therapy wash out period of 14 days * Surgery: wash-out period of 14 days * Patients must give written informed consent to participate in the study Exclusion Criteria: * Previous signs of severe toxicity platinum related * Patients must not receive any other investigational agents while on study * New York Heart Association class III or IV cardiac disease * Unstable angina * Patients with myocardial infarction within the last six (6) months * Patient with significant peripheral vascular disease * Clinical signs of CNS involvement * Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol * Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol * Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Study Objectives The main objective of this study is to assess safety, tolerability, and pharmacokinetics (PK) of ABBV-368 plus tilsotolimod; ABBV-368 plus tilsotolimod and nab-paclitaxel; and ABBV-368 plus tilsotolimod, nab-paclitaxel, and ABBV-181 in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Conditions: Advanced Solid Tumors Cancer Intervention / Treatment: DRUG: ABBV-368, DRUG: Tilsotolimod, DRUG: Nab-paclitaxel, DRUG: ABBV-181 Location: Spain, Netherlands, United States, France, Israel, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Participants should weigh at least 35 kg. * Eastern Cooperative Oncology Group performance status of 0 or 1 and a life expectancy of >= 3 months. * Participant have >= 1 lesion accessible for intratumoral injection. * Histologically or cytologically confirmed R/M HNSCC (of the following 4 subsites: oral cavity, oropharynx, larynx, and hypopharynx) who previously progressed either during or after <= 3 prior treatment regimens administered in the recurrent or metastatic setting. * Must have received 1 immunotherapy regimen which included a PD-(L)1 inhibitor. * Must have received platinum-based therapy, or be considered ineligible for platinum-based therapy by the investigator. Exclusion Criteria: * Uncontrolled metastases to the central nervous system (CNS). * Participants with brain metastases are eligible provided that evidence of clinical and radiographic stable disease for at least 4 weeks after definitive therapy is given and participants have not used prohibited levels of steroids for at least 4 weeks prior to first dose of the study. * Received prior treatment with OX40 or toll-like receptor (TLR) agonists (excluding topical agents).

Study Objectives To assess if targeting activating EGFR and HER2 mutations in Non-Small Cell Lung Cancer (NSCLC) is more effective when these mutations are truncal dominant mutations (≥50%), as opposed to non-dominant (≥5 to \<50%) or low frequency mutations (\<5%). This trial will be available to patients registered to the TRACERx study (NCT01888601), or non-TRACERx patients who have two archival tissue/DNA samples who are willing to have a biopsy of their relapsed disease. Conditions: Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Afatinib 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: * Subjects must be willing to have a biopsy of relapsed disease. Consent will be obtained through the TRACERx study or with the 'trial entry tissue collection' consent form(non-TRACERx patients). Procurement of the biopsy sample is not necessary at the time of trial registration. However, patients must undergo a biopsy prior to commencement of afatinib. * Patients must have tumours harbouring a sensitising EGFR mutation or HER2 mutation in at least one biopsy at recurrence, or region of the primary sample. * Non-TRACERx patients must have at least two archival tissue/DNA samples of their disease available. * Written informed consent for DARWIN1. * ECOG performance status 0 <= age <= 3 * No previous exposure to an EGFR TKI (other than afatinib) or HER2 targeted therapy * Measurable disease by RECIST v1.1. Patients without measurable disease may be eligible following discussion with the CI and UCL CTC but will not count towards the primary PFS endpoint. * At least 18 years. * Anticipated life expectancy of at least three months. * Adequate organ function as defined by the following baseline values: * Absolute neutrophil count (ANC) >=1.5x109/L * Platelets >=100x109/L * Serum bilirubin <=1.5 x upper limit of normal (ULN). In patients with known Gilbert's syndrome, total bilirubin <=3xULN with direct bilirubin <=1.5xULN * Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) <=3xULN or <=5x ULN if liver metastases are present * Creatinine clearance must be >=30mL/min * Women with child-bearing potential, or men who are able to father a child, must be willing to practice highly effective methods of contraception during the trial and for 1 month after the end of treatment. * Women of childbearing potential must have a negative pregnancy test within 14 days before the first dose of trial medication. Exclusion Criteria: * Currently suitable for radical radiotherapy. * Requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption or any medical comorbidity affecting gastrointestinal absorption. * Patients with current or pre-existing interstitial lung disease. * Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption, or CTCAE v4.03 Grade >=3 diarrhoea of any etiology at baseline. * Known hypersensitivity to afatinib or to any of the excipients. * Patients with rare hereditary conditions of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption * Women of childbearing potential, or men who are able to father a child, unwilling to use a highly effective method of contraception during the trial. * Anti-cancer therapy including chemotherapy, immunotherapy, biologic therapy, or major surgery within 14 days prior to start of trial therapy. * Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or syphilis infection. Subjects with evidence of hepatitis B virus clearance may be enrolled. * History of other malignancy; Exception: (a) Subjects who have been successfully treated and are disease-free for 3 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal therapy with histologically confirmed tumor lesions that can be clearly differentiated from lung cancer target and non-target lesions are eligible. * The following cardiac abnormalities: * Corrected QT (QTc) interval >=480 msecs * History of acute coronary syndromes (including unstable angina) within the past 24 weeks * Coronary angioplasty, or stenting within the past 24 weeks * Class III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system * History of known arrhythmias (except sinus arrhythmia) within the past 24 weeks * Myocardial infarction within the last 6 months * Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension etc), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to comply with the requirements of the trial, trial protocol or to provide informed consent. * Pregnant, lactating or actively breastfeeding females.

Study Objectives The purpose of this study is to find out what effects an experimental drug, called interleukin 21 or rIL-21, will have on malignant melanoma and whether these effects look promising compared to dacarbazine. In addition, this study will look at the side effects of rIL-21, and some special blood tests will be done to check the level of rIL-21 in the blood. This study will also look at previously removed melanoma tissue to determine which patients might benefit most from this treatment. This research is being done because currently there is no effective treatment for this type of cancer. Conditions: Melanoma Intervention / Treatment: DRUG: rIL-21, DRUG: Dacarbazine Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically documented cutaneous malignant melanoma which is recurrent or metastatic and is not curable by surgical or other means. * Patients must have tumour tissue from their primary and/or metastatic tumour available to assess putative molecular markers of response (paraffin block or 12 unstained slides). * Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows: Chest X-ray > 20 mm, CT scan (with slice thickness of < 5 mm) >10 mm (longest diameter), Physical exam (using calipers) > 10 mm, Lymph nodes by CT scan > 15 mm measured in short axis. All radiology studies must be performed within 21 days prior to randomization (Exception: Within 28 days if negative). * Patients must have either maximum tumour lesion size of <= 50 mm OR if tumour lesion is > 50 mm, LDH must be <= 2.5 x ULN. * Patients must have a life expectancy of at least 12 weeks. * Age > 18 years. * ECOG performance status of 0 <= age <= 1. * Previous Therapy: Immunotherapy: Prior adjuvant immunotherapy for melanoma is permitted if completed >= 1 month prior to study entry. No immunotherapy for metastatic disease is permitted. rIL-21 or dacarbazine must be the first systemic therapy for metastatic disease. Chemotherapy: Patients must not have received any prior chemotherapy (including regional therapy). rIL-21 or dacarbazine must be the first systemic therapy for metastatic disease (except for RAF and MEK-Inhibitors). Surgery: Previous surgery is permissible. Patient must be > 4 weeks since any major surgery. Radiation Therapy: Previous radiation therapy is permitted with exception of radiation therapy for brain metastases. Patients must be > 4 weeks since the last treatment with radiation. Exceptions may be made, however, for low dose, non-myelosuppressive radiotherapy. Patients must have recovered from the toxic effects of radiation. * Laboratory Requirements: (must be done within 7 days prior to randomization) Hematology: Absolute granulocytes (AGC) >= 1.5 x 109/L, Platelets >= 100 x 109/L Chemistry: Serum creatinine <= 1.5 x UNL, Bilirubin <= UNL AST and ALT <= 2.5 x UNL, LDH <= 2.5 x UNL. * Female patients of child-bearing potential must have a negative serum or urine pregnancy test within 7 days of enrollment. * Sexually active patients must agree to use a medically accepted form of contraception while receiving study therapy. * Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is given in Appendix VII. A copy of the initial REB approval and approved consent form must be sent to the central office. The patient must sign the consent form prior to randomization. Please note that the consent form for this study must contain a statement which gives permission for qualified representatives of the NCIC CTG, BMS, ZymoGenetics, the company collaborator, and regulatory authorities to review patient records (see section 16 for further details) and a statement which gives permission for NCIC CTG to access and study tissue for biomarker assessments. * Patients must be accessible for treatment and follow-up. Patients randomized on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 2 hour's driving distance) placed on patients being considered for this trial. * In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient randomization. Exclusion Criteria: * Patients with known HIV, Hepatitis B or Hepatitis C infection. * History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 5 years. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, other interventional cardiac procedure within the past 12 months, autoimmune conditions requiring chronic immunosuppressive therapy, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients may not have received any other investigational agents within 28 days of study entry, and may not receive concurrent treatment with other anti-cancer therapy or investigational agents while on protocol therapy. * Patients with known brain metastases or history of CNS metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. A head CT or MRI is required on all patients to rule out brain metastases. * Pregnant or lactating women. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with rIL-21 or dacarbazine, breastfeeding should be discontinued if the mother is treated with protocol therapy. * Prohibited Medications: Long Term (> 7 days) Systemic Corticosteroids (e.g. prednisone, dexamethasone, etc.) because these may counteract the stimulatory effects of rIL-21 on lymphocytes. (Note: Topical steroids are allowed).

Study Objectives The purpose of this study is to: 1) identify the palliative care needs of Emergency Department patients with advanced cancer, and determine if these needs can be rapidly assessed in the ED; 2) determine whether early palliative care consultation improves survival, quality of life and other burdensome symptoms and decreases utilization as compared to usual care. Conditions: Advanced Cancer, Metastatic Cancer Intervention / Treatment: OTHER: Early palliative care consultation, OTHER: Care as usual Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: HEALTH_SERVICES_RESEARCH Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * >= 18 years age * Speak English or Spanish * ED patient with an advanced solid malignancy Exclusion Criteria: * Have already been seen by palliative care team * Cognitive deficits * Children or adolescents * No confirmed history of active cancer * Do not speak English or Spanish * Reside outside the US

Study Objectives The purpose of this study is to determine the safety of multiple intravenous infusions of MORAb-004. Conditions: Solid Tumor Intervention / Treatment: DRUG: MORAb-004 (monoclonal antibody to TEM1) 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: * Subjects >=18 years. * Subjects with any malignant solid tumor without intracranial involvement or metastases diagnosed by standard pathology criteria that has failed standard chemotherapy. * Subject must have disease, as defined by RECIST or evaluable by clinical signs/symptoms (e.g., ascites, pleural effusion, or lesions of less than 2 cm) supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry. * Karnofsky performance status >=70%. * Female subjects of childbearing potential and all male subjects must consent to use a medically acceptable method of contraception throughout the study period and for 30 days after MORAb-004 administration. A barrier method of contraception must be included. * Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows: Absolute neutrophil count (ANC) >=1.5 x 109/L; Platelet count >=100 x 109/L; Hemoglobin >=10 g/dL; Serum bilirubin <=2.0 mg/dL; Aspartate transaminase (AST) <=2.5 x ULN; or <=5 x ULN if liver metastases are present; Alanine transaminase (ALT) <=2.5 x ULN; or <=5 x ULN if liver metastases are present; Serum creatinine <=2.0 mg/dL; prothrombin time (PT) and aPTT within institutional limits of normal. * Subject must be willing and able to provide written informed consent. * In Part 2 (expansion cohorts) ONLY, subjects must have a histological diagnosis of either CRC or STS (and subtypes, excluding bone sarcomas). Exclusion Criteria: * Known central nervous system (CNS) tumor involvement or metastases. * Evidence of other active malignancy. * Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months). * Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal SVT, are eligible). * Presence of severe lung disease (In the absence of clinically apparent severe lung disease, no formal testing is necessary. In the presence of clinically severe lung disease, FEV1 must be >60% in order for the subject to be eligible.) * Active serious systemic disease, including active bacterial or fungal infection. * Chronic inflammatory disorder, e.g., inflammatory bowel disease, active vasculitis. * Chemotherapy, biologic therapy, or immunotherapy within 3 weeks prior to enrollment. * Breast-feeding, pregnant, or likely to become pregnant during the study. * Active hepatitis or human immunodeficiency virus (HIV) infection. * Subjects who have received a previous monoclonal antibody therapy and have evidence of an immune or allergic reaction, or previously documented human anti-human antibody (HAHA). * Subjects with large ascites or pleural effusion (>=500 cc) based on results of most recent CT scan). * Chronic systemic anticoagulation therapy with warfarin or heparin

Study Objectives The purpose of this interventional study is to determine the feasibility to combine standard chemotherapy (Carbo/Caelyx or doxorubicin) for recurrent ovarian cancer with immunotherapy (Tocilizumab and Peg-Intron). This study combines standard chemotherapy Carboplatin-Caelyx or doxorubicin with a monoclonal antibody against IL-6R (tocilizumab). High IL-6 levels correlate with poor prognosis and chemoresistance in ovarian cancer patients. In cases of chemoresistant ovarian cancer, therefore, modulation of the IL-6 pathway, by blocking the IL-6 receptor, may represent a promising strategy to both abolish drug resistance and amplify host immunity in patients with recurrent ovarian cancer. Blockade of the IL-6/IL-6R pathway may enhance immunogenic cell death and restore local normal DC maturation. In addition, the use of interferon-alpha (Peg-Intron) allows the full maturation of DC, thereby enhancing the anti-tumor response. Conditions: Recurrent Ovarian Cancer Intervention / Treatment: DRUG: tocilizumab and interferon alpha 2-b, DRUG: Carboplatin and Caelyx or doxorubicin Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically proven epithelial ovarian cancer * Progression of disease or relapse after previous therapy with platinum * Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper normal limit (UNL) within 3 months and confirmed * Age >=18 years * WHO performance status 0 <= age <= 2 * Adequate bone marrow function: WBC >=3.0 x 109/l, neutrophils >=1.5 x 109/l, platelets >=100 x 109/l * Adequate liver function: bilirubin <=1.5 x UNL range, ALAT and/or ASAT * 2.5 x UNL (<5x UNL in case of liver metastases), Alkaline Phosphatase <=5 x UNL * Adequate renal function: the calculated creatinine clearance should be * 50 mL/min * Survival expectation > 3 months * Patients must be accessible for treatment and follow-up * Written informed consent according to the local Ethics Committee requirements Exclusion Criteria: * Chemotherapy within past 3 months * 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 * Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias * Known hypersensitivity reaction to any of the components of the treatment * Pregnancy or lactating * Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent * Infection with tuberculosis and hepatitis B or C

Study Objectives This is a non-randomised study assessing the technique of using indocyanine green as a fluorescent dye to highlight the thoracic duct during oesophectomy. Conditions: Chylothorax, Esophageal Cancer, Thoracic Duct Intra-Operative Injury Intervention / Treatment: DRUG: Indocyanine Green Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: OTHER Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the study. * Male or Female, aged 18 years or above. * Undergoing elective oesophagectomy Exclusion Criteria: * Known allergy to iodine or ICG * Female patient who is pregnant, planning pregnancy or breastfeeding * Patient has a lactose intolerance (excluded only from receiving cream method) * Known significant liver failure

Study Objectives To estimate the real-world rates of recurrent Venous thromboembolism (VTE), major bleeding and all-cause mortality in patients with Cancer-associated thrombosis (CAT) treated with rivaroxaban Conditions: Venous Thromboembolism Intervention / Treatment: DRUG: Rivaroxaban (Xarelto, BAY59-7939) Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Adult patients (>=18 years-of-age) with active cancer * Patient with at least one index venous thromboembolism (VTE ) * >=6-months of continuous eligibility prior to the index VTE event (baseline period). * Newly initiated on rivaroxaban Exclusion Criteria: * Patients with any medical claim for Deep vein thrombosis (DVT) or Pulmonary embolism (PE) during the 6 months pre-index date * Patients with prescription claim for anticoagulation therapy during the 6-month pre-index VTE period

Study Objectives Despite significant progress in overall survival and event-free survival in Pediatric Hematopoietic Stem Cell Transplant (HSCT), therapeutic options for graft-versus-host disease control remain limited, particularly in steroid-refractory patients. Several strategies have been proposed in the last 20 years but so far, the results have been inconclusive, complicated by the small population afflicted, inconsistent treatment schedules, different disease classifications and diagnosis methods. The number of studies concerning pediatric patients are even smaller. First line therapy for acute graft-versus-host disease (aGVHD) is steroid treatment that achieve partial or complete remission of the disease in a variable percentage of cases (40-60%), depending mainly to severity of GVHD and number of organ involvement, with hepatic and gastrointestinal GVHD particularly refractory to steroid treatment. For second line therapy there is no a standardized strategy with a great variety of immunosuppressive treatment without a real superiority of a drug in comparison to another. Steroid refractory acute GVHD is therefore one of the most important challenges in HSCT field. One of the more promising routes, based on published data and clinical experience, is the off-label use of Infliximab, an anti-Tumor Necrosis Factor α drug (already approved for many rheumatologic and autoimmune diseases) administered as a second line treatment in patients with steroid-refractory aGVHD at the standardized dosage of 10 mg/kg, although limited evidence has been published to validate this subscription. Biological pattern that could explain susceptibly of GVHD to infliximab treatment could lie in physiopathology of acute gastrointestinal GVHD that may resemble ulcerative rectocolitis. In this case, relation to Therapeutic Drug Monitoring (TDM) and Tumor Necrosis Factor α (TNFα) levels could be critical in monitoring the efficacy of the drug and need of further doses. Limited published data and clinical experience show that Infliximab may be able to further control symptoms and inflammatory response in a promising percentage of treated patients, although some have no benefit from the treatment. The aim of this study is to analyze the role of TNFα concentration in aGVHD, its levels fluctuation and clinical response of GVHD to Infliximab treatment in steroid-refractory pediatric patients. Conditions: Acute Graft-versus-host Disease Location: Italy Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age of the patients between 0 and 18; * Allogeneic HSCT recipient; * Onset of clinical signs of acute skin, gastrointestinal or hepatic GVHD according to the Glucksberg classification; * At least five days of steroid treatment (minimum 1 mg/kg of methylprednisone or equivalent) for systemic aGVHD without clinical or laboratory signs of response or no steroid treatment for onset of grade I-II hepatic/gastroesophageal/intestinal isolated aGVHD; * Patients who consent for the off-label use of infliximab and data processing for research purposes; * At least one dose of infliximab received during aGVHD management; * Minimum follow-up after infliximab administration of 6 months Exclusion Criteria: * Active fungal or bacterial infection with life-threatening clinical condition (shock or respiratory distress needing mechanical ventilation)

Study Objectives The purpose of this study is to define the Maximum tolerated dose of SU14813 when administered as single agent in patients with solid tumors. Conditions: Neoplasms, Solid Tumors Intervention / Treatment: DRUG: SU014813 Location: Germany, Netherlands 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 a histologically proven advanced solid malignancy for which no recognized therapy was available or for which standard therapy had failed * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Serum albumin >=3.0 g/dL and adequate haemopoietic, renal and liver function Exclusion Criteria: * Chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy or an investigational agent within 4 weeks before the start of study treatment * Subjects had to have recovered from all prior treatment toxicities, except alopecia, and from any major surgery.

Study Objectives The primary objective of this study is aimed at analyzing the ICU triage practices of clinicians at a cancer hospital with and without the use of an algorithm-based triage tool, and to assess whether or not the triage tool improves the consensus amongst practioners on the prioritization of patients for ICU admission. Secondary objectives include assessment of whether or not triage practices based on guidelines correlate with what is done in actual practice. Conditions: Intensive Care Units, Triage Intervention / Treatment: BEHAVIORAL: Survey, BEHAVIORAL: Algorithm-based Triage Tool Location: Ecuador, United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: 1) Study participant must be a health care provider who frequently refers or accepts oncologic patients to the ICU Exclusion Criteria: 1) none

Study Objectives Despite these initial positive signals in recent statistics, breast cancer continues to claim a substantial number of lives approximately 500,000 deaths worldwide in 2005 Thus the current treatment paradigm - surgery, radiation and systemic chemo and or hormonal therapy and biological therapies -still fails to cure a significant number of women with early breast cancer and new treatment strategies are needed to improve current results both in early and advance disease. Recurrent or metastatic breast cancer is an incurable malignancy with a median survival of 20-24 months \[Hortobagyi , 1998\] and this has not changed significantly over the last decade with fewer than 20% of patients still alive at 5 years after a diagnosis of recurrence. Although there have been small improvements in survival with the new therapies, metastatic breast cancer remains an incurable and, ultimately, fatal disease. The introduction of novel combination therapies have the potential to target different pathways in the cancer cell, leading to improved efficacy. Further studies to optimize combination therapy, while ameliorating AEs, are critically important to patients with metastatic breast cancer. Lapatinib is an oral tyrosine kinase inhibitor which potently inhibits both EGFR and HER2\[Spector, 2005\]. Lapatinib in combination with capecitabine is approved in more than 20 countries for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2. All patients in the study leading to the lapatinib approval had received prior therapy including an anthracycline, a taxane, and trastuzumab. The relevance of the HER2/neu target in breast cancer, combined with the promising preclinical and clinical data regarding the use of lapatinib, provide the rationale for a formal evaluation of this agent combined with other non taxane agents as gemcitabine or vinorelbine after progression on taxanes and trastuzumab based therapies in metastatic disease setting as these chemotherapy options are used in daily practice in this subset of patients. This is a randomized phase II, open label,multicentric , international, 3 arms treatment study in patients with confirmed HER2+ metastatic breast cancer after taxane progression . The main objective is to investigate the (CBR) and safety in 3 different combinations of Lapatinib therapy (plus capecitabine or gemcitabine or vinorelbine) and to determine whether either, or both, of Lapatinib /Vinorelbine or Lapatinib/Gemcitabine can be considered a reasonable alternative to the established Lapatinib/Capecitabine standard combination . The decision as to whether to study either of the new combinations further will be based on both the toxicity and the efficacy profiles. Conditions: BRMS1, Performance Status Zero to Two for Beginning the Study, Patient With a Maximum of One Chemotherapy, Patient With Progression After Taxanes Intervention / Treatment: DRUG: Lapatinib Vinorelbine, DRUG: Lapatinib Capecitabine, DRUG: Gemcitabine Lapatinib Location: Brazil, Peru, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed informed consent must be obtained according to local ethical committee requirements. * Subjects must be older than 18 years. * Histologically confirmed invasive adenocarcinoma of the breast which is stage IIIb, stage IIIc with T4 lesion, or stage IV disease [according to AJCC 6th edition] * Documented progression after taxane based treatment for ErbB2 positive patients for 1st line metastatic breast cancer or documented progression after taxane based regimens as adjuvant or neo-adjuvant therapy. Patients may have had a maximum of one prior treatment with a chemotherapy regimen for metastatic disease. * Patients must have at least 1 measurable lesion defined by RECIST as follows: * X-ray, physical exam > 20 mm. * Conventional CT scan > 20 mm. * Spiral CT scan > 10 mm. * Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease. * Local laboratory confirmed HER2/neu over expressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by at least one of the following based local results: * 3+ overexpression by IHC (> 30% of invasive tumour cells). * 2+ or 3+ (in 30% or < % of neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification. * HER2 gene amplification by FISH or CISH. (> 6 HER2 gene copies per nucleus, or a FISH ratio (HER2 gene copies to chromosome 17 signals) of > than 2.2. * Prior therapy must have included a taxane regimen. Patients must have received either: * Prior adjuvant treatments with taxanes-containing chemotherapy regimens providing that at least 6 months has elapsed from the last dose of adjuvant or neoadjuvant chemotherapy and all treatment related adverse events are < grade 1 at the time of randomization; OR * Prior treatment with taxane based chemotherapeutic regimens for first line metastatic breast cancer or prior taxane based neoadjuvant regimens for locally advanced disease providing that at least 4 weeks has elapsed since the last dose of therapy for metastatic disease and all treatment related adverse events are < grade 1 at the time of randomization. * In regions where trastuzumab is available with no barriers to access, patients must have also received prior trastuzumab alone or in combination with chemotherapy in order to be eligible as follows: * Prior treatment with Trastuzumab includes only first line metastatic setting; OR * Prior trastuzumab treatment in neoadjuvant / adjuvant setting provided that at least 6 months has elapsed from last dose of adjuvant / neoadjuvant Trastuzumab , and all treatment related adverse events are < grade 1 at the time of randomization. * Prior treatment with anthracyclines in the adjuvant or first line metastatic setting are permitted provided that therapy has been discontinued before randomization, and all treatment related adverse events are < grade 1 at the time of randomization. * Prior treatment with endocrine therapy in the adjuvant or metastatic setting are permitted provided that therapy has been discontinued before randomization, and all treatment related adverse events are < grade 1 at the time of randomization. * Prior treatments with radiation therapy for palliative management of metastatic disease , to a limited area (e.g., palliative treatment for painful disease) other than the sole site of measurable and assessable disease is allowed however, subjects must have completed treatment at least 4 weeks of the last dose of radiotherapy prior to starting study drugs, and must have recovered from all treatment-related toxicities prior to Day 1. * Life expectancy of at least 6 months. * ECOG PS 0 <= age <= 2. * Patients must have normal organ and marrow function measured within 14 days prior to randomization as defined below: * System Laboratory Values * Hematologic * Absolute neutrophil count (ANC) > 1.5 X 109/L * Hemoglobin1 > 9 g/dL * Platelets > 100 X 109/L * Hepatic * Albumin > 2.5 gr /dl * Total bilirubin > 1.5 X upper limit of normal (ULN) * AST and ALT > 2.5 X ULN * Renal * Serum Creatinine > 1.5 mg/dL o 132.6 micromol/L * Or, if serum creatinine > 1.5 mg/dL, Calculated creatinine clearance > 50 mL/min * Patients may not have had a transfusion within 7 days of screening assessment 14. CT head/MRI within 4 weeks prior to randomization. 15. Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to registration. 16. Patients must have at least 1 measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, Therasse, 2000). Measurable lesions may be in the field of prior adjuvant irradiation. However, there must be at least a 4 week period between the last radiation treatment and the baseline scan documenting disease status. Documented progression of the irradiated lesion is also required for the lesion to be considered measurable. 17. Subjects must have a cardiac ejection fraction within the institutional range of normal as measured by ECHO (echocardiogram) or alternatively by MUGA (Multigated Acquisition) scan. Cardiac ejection fraction > 50% and within the institutional range of normal as demonstrated by echocardiogram or alternatively by MUGA scan within 4 weeks of randomization Subjects with known uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are NOT eligible; 18. Subjects must complete all screening assessments as outlined in the protocol. Exclusion Criteria: * Pregnant or lactating women. * Prior therapy with other anti Erbb1 or antiErbB2 targeted agent rather than Trastuzumab only limited to 1st line treatment of metastatic disease OR as adjuvant/neoadjuvant therapy. * Prior exposure to gemcitabine , vinorelbine and capecitabine for 1st line treatment of recurrent-metastatic disease OR as adjuvant / neoadjuvant therapy. * Treatment in the 14 days prior to randomization with anti-cancer therapy (tumor embolization, chemotherapy , immunotherapy, biological therapy, or hormonal therapy) or treatment with mitomycin within 6 weeks prior to randomization. Such treatment may not be resumed or begun after study entry. Note: Patients receiving bisphosphonate therapy prior to randomization may continue for the duration of study participation, however bisphosphonates should not be initiated following study entry. Prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for the treatment of osteoporosis. * Active CNS metastases. * Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious non-healing wound/ulcer/bone fracture, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis). * Have current active hepatic or biliary disease(with exception of patients with Gilbert syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) * History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. * Concurrent treatment with an investigational agent or participation in another clinical trial. * Used an investigational drug within 30 days or 3 half-lives, whichever is longer, preceding the first dose of therapy. * History of immediate or delayed hypersensitivity or idiosyncrasy to drugs chemically parented to Lapatinib or navelbine or capecitabine or gemcitabine and its excipients.

Study Objectives This study will evaluate the efficacy and safety of nilotinib in gastrointestinal stromal tumors patients who failed imatinib and sunitinib therapy. Conditions: Gastrointestinal Stromal Tumors Intervention / Treatment: DRUG: AMN107 Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Documented disease progression during imatinib and sunitinib therapy OR intolerance to imatinib and/or sunitinib * At least one measurable site of disease on CT/MRI scan * PS<=2 * Normal organ, electrolyte, and bone marrow function Exclusion Criteria: * Previous treatment with nilotinib or any other drug in this class or other targeted therapy * Treatment with any cytotoxic and/or investigational drug <= 4 weeks prior to study entry * Impaired cardiac function * Use of coumarin derivatives (i.e. warfarin) * Women who are pregnant or lactating Other protocol-defined inclusion/exclusion criteria may apply.

Study Objectives This study is single-arm, none randomized, open label, two-dose-cohorts, single center clinical trial for evaluation of the safety and efficacy of Oshadi D and Oshadi R in patients with BCC. Patients will receive Oshadi D and Oshadi R for 60 -90 days until the planned surgical excision of the lesion. Conditions: BCC Intervention / Treatment: DRUG: Oshadi D & Oshadi R Location: Israel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age > 21 years with tissue confirmed diagnosis of local BCC. * Patient is candidate for surgical excision of the BCC in few months. * BCC lesion >=10mm in its longest diameter. * Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception during therapy and 3 months after the last dose of the study drugs. * Female patients of childbearing potential must have a negative pregnancy test at screening. * Patient must understand and be willing to give written informed consent prior to any study procedures or evaluations and be willing to adhere to all study schedules and requirements. Exclusion Criteria: * Uncontrolled Intercurrent illness or any history of significant cardiac, renal, neurologic, metabolic, pulmonary, gastrointestinal, hematologic abnormality, chronic hepatic disease or any other disease which in the judgment of the investigator would interfere with the study or confound the results. * Other active cancer disease. * Serum creatinine > 1.5 mg/dL for males and >1.4 mg/dL for females. * Female patient who are breastfeeding or have a positive pregnancy test at screening or at any time during the study. * Any acute cardiovascular event during the last 6 months prior to inclusion. * Symptomatic congestive heart failure with ejection fraction < 30%. * Patient has prothrombin time/International Normalization Ration (PT/INR) or partial thromboplastin time (PTT) test results > 1.3 UNL. * Hemoglobin <= 11 g/dL * Platelets < 150,000 per microliter * White blood cell count<3,000 x109/L and/or absolute neutrophils count <1.5 x 109/L * Significant swallowing disorders. * History of small bowel surgery. * Any history of pelvic or abdominal radiation. * Pre-existing mal-absorption syndrome, irritable bowel syndrome or other clinical situation which could affect oral absorption. * Mental disorders. * Inability to give written informed consent.

Study Objectives The purpose of this research study is to determine the safest and most effective dose of 5-FU that can be given with docetaxel (Taxotere), Cisplatin and cetuximab to patients with newly diagnosed locally advanced squamous cell carcinoma of the head and neck. We will also be studying the toxicity of this regimen of 4 drugs and the tumor response. Conditions: Head and Neck Neoplasms Intervention / Treatment: DRUG: Cetuximab, DRUG: Docetaxel, DRUG: Cisplatin, DRUG: 5-Fluorouracil 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: * Histologically or cytologically proven squamous cell carcinoma of the head and neck. * Primary tumor sites eligible: oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Unknown primary SCC will also be eligible. * Stage 3 or 4 disease without evidence of distant metastases verified by chest x-ray, abdominal ultrasound or CAT scan. * At lease one uni- or bi-dimensionally measurable lesion by RECIST criteria. * 18 years or older * ECOG performance status of 0 <= age <= 1 * Adequate bone marrow, hepatic and renal functions as outlined in the protocol. Exclusion Criteria: * Pregnant or breast feeding women * Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years. * Symptomatic peripheral neuropathy greater or equal to grade 2 * Symptomatic altered hearing > grade 2 by CIT-CTC criteria * Unstable cardiac disease despite treatment, myocardial infarction within 6 months * History of significant neurologic or psychiatric disorders including dementia or seizures * Active clinically significant uncontrolled infection * Active peptic ulcer disease defined as unhealed or clinically active * Hypercalcemia * Active drug addiction, including alcohol, cocaine or intravenous drugs use * Chronic Obstructive Pulmonary Disease * Autoimmune disease requiring therapy, prior organ transplant, or HIV infection * Interstitial lung disease * Involuntary weight loss of more than 25% of their body weight in the 2 months preceding study entry * Concurrent treatment with any other cancer drug * Prior EGFR therapy * Prior severe infusion reaction to antibody therapy * Participation in an investigational trial within 30 days of study entry

Study Objectives In the First-in-Human, JWAA trial, the LY2780301 displayed a favourable safety profile, a high pharmacokinetic exposure and the ability to decrease pS6. LY2780301 has shown synergistic activity in combination with targeted agents or chemotherapy including gemcitabine. We propose herein to combine LY2780301 with gemcitabine and to treat different tumor types with molecular alterations. This may validate the anti-tumor activity of the LY2780301 and it will increase our knowledge regarding molecular predictors of its efficacy. Conditions: Solid Tumors and Non-Hodgkin's Lymphoma Intervention / Treatment: DRUG: LY2780301, DRUG: Gemcitabine Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) with selected molecular alterations and for which no proven effective therapy exists. ; * Dose Confirmation portion (Part 2): have histological or cytological evidence of cancer (solid tumor or Non-Hodgkin's Lymphoma) that is advanced and/or metastatic disease: * Cohort A: Up to 20 patients of any histological type (solid tumor or Non-Hodgkin's Lymphoma) with selected molecular alterations * Cohort B: Up to 12 patients with ovarian cancer and with selected molecular alterations 1.1 (Appendix 4) for solid tumors or by the Revised Response Criteria for Malignant Lymphoma Dose Confirmation portion: * Measurable disease as defined by RECIST 1.1 for solid tumors (Appendix 4) except ovarian cancer or * Response Criteria for Patients with Ovarian Cancer Who Have Evaluable but Non-Measurable Disease (Appendix 5) or * Revised Response Criteria for Non-Hodgkins Lymphoma (Appendix 6) [4] Are >=18 years ; [5] Written informed consent ; [6] Have adequate organ function including: * Hematologic: absolute neutrophil count (ANC) >=1.5 x 109/L, platelets >=100 x 109/L, and hemoglobin >=9 g/dL. * Hepatic: bilirubin <=1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and AST <=2.5 x ULN. (<=5 x ULN if the liver has tumor involvement). * Renal: Serum creatinine <=1.5 x ULN or calculated creatinine clearance >45 ml/min (MDRD) [7] ECOG performance status <= 1 ; [8] Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrolment and all prior treatment related toxicities must be CTCAE (Version 4.0) <= Grade 1 (except alopecia) at the time of enrolment. Patients with prostate cancers progressing under LHRH agonist therapy, may have that treatment continued while receiving study drug ; [9] Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug ; [10] Females with childbearing potential must have had a negative serum pregnancy test <= 14 days prior to the first dose of study drug ; [11] Have an estimated life expectancy >=12 weeks ; [12] Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels ; Exclusion Criteria: [13] Any serious and/or unstable pre-existing medical conditions, psychiatric disorder, or other conditions that could, in the opinion of the investigator, interfere with subject's safety, obtaining informed consent or compliance to the study procedures ; [14] Have symptomatic CNS malignancy or symptomatic brain metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable and asymptomatic and they are not currently receiving corticosteroids. Screening of asymptomatic patients without history of CNS metastasis is not required ; [15] Have pre-existing not controlled cardiovascular disease (including acute coronary syndromes, unstable angina, coronary angioplasty, or stenting within the past 6 months) or any QTc prolongation (defined as a QTc interval > 480 ms according to Friedericia's correction) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (HR < 50 bpm), or any history of 2nd or 3rd degree block ; [16] Concomitant treatment prohibited in section 7.8 ; [17] Pregnancy and Breast Feeding ;

Study Objectives This phase II trial is studying the side effects of pazopanib hydrochloride and to see how well it works in treating patients with metastatic melanoma that cannot be removed by surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Conditions: Recurrent Melanoma, Stage IV Cutaneous Melanoma AJCC v6 and v7 Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, DRUG: Pazopanib Hydrochloride, OTHER: Pharmacological Study 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: * Histologically confirmed unresectable malignant melanoma * Radiographic or clinical evidence of metastatic disease * Measurable disease with >= 1 lesion whose longest diameter can be measured as >= 2.0 cm by CT or MRI scans or >= 1.0 cm by spiral CT scan * Disease that is measurable by physical examination only is not allowed * No known intraluminal metastatic lesion(s) with suspected bleeding * No brain metastases by MRI or CT scan * ECOG performance status 0 <= age <= 2 * Life expectancy > 12 weeks * WBC >= 3,000/μL * Hemoglobin >= 9 g/dL * Absolute neutrophil count >= 1,500/μL * Platelets >= 100,000/μL * Total bilirubin <= 1.5 times upper limit of normal (ULN) * AST and ALT <= 2.5 times ULN * Creatinine <= 1.5 times ULN * Serum troponin normal * Urine protein <= 1+ (<= 30 mg/dL) on 2 consecutive dipstick or other urine assessments taken >= 1 week apart * QTc interval < 480 msec * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia) * No serious nonhealing wound, ulcer, or bone fracture * No history of abdominal fistula, gastrointestinal perforation, active diverticulitis, intra-abdominal abscess, or gastrointestinal tract bleeding within the past 28 days * No history of myocardial infarction, cardiac arrhythmia within the past 6 months * No NYHA class III-IV heart failure * Patients with a history of class II heart failure and who are asymptomatic on treatment may be eligible * No history of bleeding disorder, including hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding * No uncontrolled infection * No evidence of active bleeding or bleeding diathesis * No hemoptysis within 6 weeks of first dose of study drug * No active peptic ulcer disease * No inflammatory bowel disease * No ulcerative colitis or other gastrointestinal conditions with increased risk of perforation * No history of cerebrovascular accident, including transient ischemic attack, pulmonary embolism, or untreated deep venous thrombosis within the past 6 months * Patients with recent deep vein thrombosis who have been treated with therapeutic anticoagulating agents within the past 6 weeks are eligible * No known endobronchial lesions or involvement of large pulmonary vessels by tumor * No current active hepatic or biliary disease, except Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease * No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg and diastolic BP > 90 mm Hg) * No condition that impairs ability to swallow and retain pazopanib hydrochloride (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) * No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study * No 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 * No admission for unstable angina, cardiac angioplasty, or stenting within the past 6 months * More than 6 weeks since prior major surgery * More than 4 weeks since prior and no concurrent radiotherapy * At least 14 days or 5 half-lives and no concurrent CYP interactive medications * No prior radiotherapy to >= 25% of bone marrow * No prior therapy with a VEGFR tyrosine-kinase inhibitor * No concurrent antiretroviral therapy for HIV-positive patients * No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride * No concurrent chemotherapy * No other concurrent investigational agents * No other concurrent anticancer agents or therapies * No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes