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Study Objectives According to the World Health Organization, breast cancer is the most common cancer in women, and is responsible for 686,000 new cases every year. The WHO also posit that nearly 420,000 women perished from the disease in 2002. Surgery remains the best option for patients presenting with operable Stage I, II or III cancers. Breast conservation surgery has been shown to be as efficacious as mastectomy. About 60-70% of these women with operable breast cancer are breast conservation candidates. However, the need to achieve negative tumor margins often requires a second operation (re-excision) in up to 70% of the women having lumpectomy surgery. Currently, tumor margins assessment in the operating room is often assessed grossly by palpation. The ability to evaluate tumor margin using our proposed intraoperative imaging technique may provide the surgeon with an alternative, and hopefully, more sensitive method to assess tumor margins which may decrease re-excision and the morbidity associated with additional surgery, and, perhaps, lower the risk of local regional recurrence. Conditions: Invasive Ductal Carcinoma, Invasive Lobular Carcinoma, Ductal Carcinoma Intervention / Treatment: DRUG: Indocyanine Green Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult patients over 18 years of age * Women with newly diagnosed, operable invasive ductal carcinoma, invasive lobular carcinoma or ductal carcinoma who are deemed breast conservation surgery candidates (i.e. lumpectomy +/- sentinel node biopsy). * Breast cancer needs to be unifocal as determined by clinical parameters, e.g. by palpation or by breast imaging findings including mammogram, US and/or breast MRI. Multifocal disease, i.e. cancer confined to one quadrant, is eligible if patients are deemed breast conservation candidates. * Subject capable of giving informed consent and participating in the process of consent. Exclusion Criteria: * Newly diagnosed breast cancer patients who are not breast conservation candidates and those with multicentric breast cancer (breast cancer documented in multiple quadrants by breast imaging or exam) * Pregnant women as determined by urinary or serum beta human chorionic gonadotropin (hCG) within 72 hours of surgery * Subjects with a history of iodide allergies * At-risk patient populations 1. Homeless patients 2. Patients with drug or alcohol dependence 3. Patients unable to participate in the consent process

Study Objectives This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin to patients with locally advanced or metastatic solid tumors. Conditions: Solid Cancers Intervention / Treatment: DRUG: GDC-0980, DRUG: bevacizumab, DRUG: carboplatin, DRUG: cisplatin, DRUG: paclitaxel, DRUG: pemetrexed Location: United States, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy * Adequate hematologic and end organ function * For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study * Measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors), with the exception of prostate cancer (two rising PSA Levels that meet the criteria of progression per PSA Working Group) and ovarian cancer (two rising CA-125 levels greater than the ULN) Exclusion Criteria: * Current dyspnea at rest due to complications of advanced malignancy, or other conditions requiring continuous supplemental oxygen * Uncontrolled hypomagnesemia or hypokalemia * History of Grade >= 3 fasting hyperglycemia * Any condition requiring full-dose anticoagulants * Known HIV infection * Known untreated or active central nervous system (CNS) metastases * Pregnancy, lactation, or breastfeeding * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study * For Arm B: Conditions that preclude the use of bevacizumab * For Arm C: Conditions that preclude the use of pemetrexed or cisplatin

Study Objectives The investigators are interested in enrolling patients with rheumatoid arthritis (RA) who had a difficult time getting their disease under control even after trying multiple RA therapies. The investigators believe that there may be common patterns in the genes of this group of RA patients compared to those with more "textbook RA." Understanding genetic factors can help doctors to know in advance who may not respond to conventional therapies and start with treatments that work. Learning about underlying genes that influence treatment may help the investigators to identify new targets for therapy, to ultimately improve the lives of patients with RA and inflammatory arthritis. Conditions: Rheumatoid Arthritis Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age > 18 years * RA diagnosed by a rheumatologist * Poor control of RA disease activity with tumor necrosis factor inhibitor (TNFi) and another biologic therapy or small molecule approved for RA Exclusion Criteria: * If the reason for failed TNFi therapy was due to a contraindication or adverse reaction * Unable to provide blood sample

Study Objectives The study is aimed to confirm that letrozole + PD 0332991 is safe and tolerable and to assess the effect of the combination on advanced breast cancer Conditions: Breast Cancer Intervention / Treatment: DRUG: PD 0332991, DRUG: letrozole, DRUG: letrozole Location: Hungary, Germany, Canada, Korea, Republic of, Italy, Spain, Ukraine, United States, Ireland, South Africa, Russian Federation, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Masking: NONE

Inclusion Criteria: * Inoperable estrogen receptor positive and HER2 negative breast cancer. * Postmenopausal status. * Tumor tissue (archived acceptable) available for biomarker studies. For Phase 2 Part 2 - CCND1 amplification and/or loss of p16 as determined by the central laboratory. * Acceptable bone marrow, liver and kidney function. Exclusion Criteria: * Prior or concomitant treatment for advanced breast cancer. * Other major cancer in the past 3 years. * Important cardiovascular events in the past 6 months.

Study Objectives The purpose of this study is to evaluate the safety and effectiveness of TGR-1202 in combination with brentuximab vedotin in patients with hodgkin's lymphoma. Conditions: Hodgkin's Lymphoma Intervention / Treatment: DRUG: TGR-1202 + brentuximab vedotin 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: * Confirmed diagnosis of Hodgkin's Lymphoma * Relapsed or refractory after an autologous stem cell transplant (ASCT) or at least two prior multi-agent chemotherapy regimens in patients not candidates for ASCT * Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Exclusion Criteria: * Any major surgery, chemotherapy or immunotherapy within the last 21 days * Known hepatitis B virus, hepatitis C virus or HIV infection * Autologous hematologic stem cell transplant within 3 months of study entry. Patients who had prior Allogeneic hematologic stem cell transplant are excluded

Study Objectives The purpose of the study, is to determine the percentage of patients for whom the initial LHRH prescription has been renewed Conditions: Prostate Cancer Intervention / Treatment: DRUG: LHRH analogues Location: Spain Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Adult men diagnosed of locally advanced or metastatic prostate cancer scheduled to receive androgen deprivation therapy with a 3 or 6 month LHRH analogue including those requiring neo-adjuvant or adjuvant androgen deprivation therapy in association with radiotherapy * Patients having provided written informed consent * Patients mentally fit for completing a self-administrated questionnaire Exclusion Criteria: * Patients participating in another clinical study at the time of inclusion * Patients with another severe malignant disease * Life expectancy of less than 12 months * Patients already treated with a LHRH analogue within the last year

Study Objectives The purpose of this Phase I study is to test the safety and effect of specially prepared cells collected from the patients called "modified T cells." We want to find a safe dose of modified T cells for patients who have disease remaining after initial chemotherapy. We also want to find out what effects these T cells have on you and your leukemia. Conditions: Leukemia Intervention / Treatment: DRUG: cyclophosphamide, BIOLOGICAL: modified T cells 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: * CLL patients with evidence of residual disease, who have achieved PR, nPR or CR with detectable MRD following upfront therapy consisting of pentostatin, cyclophosphamide and rituximab. * The presence of MRD will be assessed by the flow cytometry and polymerasechain reaction at the MSKCC Diagnostic Molecular Pathology Laboratory. * Age ≥ 18 years of age. * Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support. * Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry. Exclusion Criteria: * Karnofsky performance status <70. * Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished. * Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan. * Patients previously treated with allogeneic bone marrow or stem cell transplantation are ineligible. * Patients who are immediate candidates for allogeneic bone marrow or stem cell transplantation. Patients who refuse this option remain eligible and need to be documented as such in patient medical record. * CLL patients with transformed disease (Richter's transformation) are ineligible for enrollment on this study. * Patients with following cardiac conditions will be excluded: * New York Heart Association (NYHA) stage III or IV congestive heart failure * Myocardial infarction ≤6 months prior to enrollment * History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration * History of severe non-ischemic cardiomyopathy with EF ≤20% * Patients with HIV and active hepatitis B or hepatitis C infection are ineligible. * Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation, with the exception of squamous and basal cell carcinoma of skin. STEP 2 REGISTRATION (Treatment): The following additional criteria must be met in order for a patient to be eligible to receive the modified T cell infusion. These labs are to be obtained within 2 weeks of T cell infusion. * Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support.

Study Objectives This is an open-label, 2 part study of pazopanib and/or MK 3475 in treatment naïve subjects with advanced RCC. Part 1 consists of a Phase I dose escalation of pazopanib + MK 3475 followed by an expansion cohort to determine the maximum tolerated regimen and the recommended Phase II dose. Part 2 is a randomized 3-arm Phase II study to evaluate the clinical efficacy and safety of pazopanib + MK 3475 as compared to single-agent pazopanib and single-agent MK 3475. The objectives of this Phase I/II study are to test the safety and tolerability of pazopanib in combination with MK 3475, and study the clinical efficacy of pazopanib in combination with MK 3475 in subjects with advanced RCC as compared with single-agent pazopanib and single-agent MK 3475. Following the Urgent Safety Measure (USM) released on February 09, 2017, the phase II (Part 2) portion of this study will not commence. Conditions: Carcinoma, Renal Cell Intervention / Treatment: DRUG: Pazopanib, DRUG: MK-3475 Location: United States, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Signed written informed consent before performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up * Diagnosis of locally advanced or metastatic RCC that is predominantly clear cell histology * Must have measurable disease * Subject has received no prior systemic therapy * A woman is eligible to participate in the study if she is of Non-childbearing potential, has a negative serum pregnancy test within 7 days of the first dose of study treatment, not lactating, and agrees to use adequate contraception during the study until at least 120 days after the last dose of investigational product * Eastern Cooperative Oncology Group performance status 0 or 1 * Adequate organ function as defined in the protocol * Left ventricular ejection fraction >= lower limit of normal as assessed by echocardiogram or multigated acquisition scan * In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category Exclusion Criteria: * Subject has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents * Subject is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study treatment * Subject is expected to require any other form of systemic or localized antineoplastic therapy while on study * Subject is on any systemic steroid therapy, within one week before the planned date for first dose of study treatment. Subject is on any other form of immunosuppressive medication * Subject has a history of a malignancy (other than the disease under treatment in the study) within 5 years before first study treatment administration * Central nervous system metastasis * Unable to swallow and retain orally administered medication * Subject has interstitial lung disease or a history of pneumonitis * Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other Gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, GI perforation, or intra-abdominal abscess within 4 weeks before beginning study treatment * Known history of HIV infection or a known history of or is positive for Hepatitis B or Hepatitis C * Presence of active infection requiring systemic therapy * Corrected QT interval duration prolongation * History of any one or more of the following cardiac conditions within the past 6 months: Cardiac angioplasty or stenting; Myocardial infarction; Unstable angina; History of Class III or IV congestive heart failure according to New York Heart Association classification * History of cerebrovascular accident within the past 6 months * Poorly controlled hypertension * History of untreated deep venous thrombosis * Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Recent hemoptysis * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage * Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures * Previous severe hypersensitivity reaction to another Monoclonal antibody. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the excipients in pazopanib tablets * Has taken any prohibited medications that are listed in the protocol within 14 days of the first dose of study treatment. Subject has received or will receive a live vaccine within 30 days before the first administration of study treatment

Study Objectives The purpose of this study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous Rituximab-miniCHOP + lenalidomide) and R-miniCHOP (Sub-cutaneous Rituximab-miniCHOP) in patients aged 80 years old or more with not previously treated cluster of differentiation antigen 20 positive (CD20+) diffuse large B-cell lymphoma as measured by the overall survival (OS).The SENIOR trial will evaluate the tolerance and efficacy of the combination of the R2-miniCHOP regimen and compare this experimental arm to the standard R-miniCHOP regimen.The statistical plan is based on the hypothesis of an increase by 15% of the 2y-OS in favor of the experimental arm, as compared to the reference arm (R-miniCHOP). Conditions: Diffuse Large B Cell Lymphoma Intervention / Treatment: DRUG: Lenalidomide, DRUG: Rituximab Location: Belgium, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including all clinical subtypes (primary mediastinal, intravascular, etc...), with all age-adjusted International Prognostic Index (aaIPI). May also be included: De Novo transformed DLBCL from low grade lymphoma (Follicular, other...) and DLBCL associated with some small cell Infiltration in bone marrow or lymph node; or CD20+ B-cell lymphoma, with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma; or CD20+ Follicular lymphoma grade 3B (according to WHO classification); or CD20+ Aggressive B-cell lymphoma unclassifiable. * With a Cluster of Differentiation antigen 10 (CD10) immunostaining performed by the participating center pathologist * Aged ≥ 80 years old * Ann Arbor stage II, III or IV * Patient previously untreated for DLBCL Lymphoma * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * With a minimum life expectancy of 3 months * Negative HIV, HBV and HCV serologies test within 4 weeks before inclusion (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative) * Patient able to give his consent and having signed a written Informed consent * Patient affiliated to social security system, if applicable * Male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 3 months following study drug discontinuation, even if they have undergone a successful vasectomy. * All patients must agree to fulfill the global Lenalidomide Pregnancy Prevention Risk Management Plan as applicable according to the randomization arm (randomization arm) Exclusion Criteria: * Any other histological type of lymphoma, Burkitt included * Any history of treated or non-treated small-B cell lymphoma * Central nervous system or meningeal involvement by lymphoma * Contra-indication to any drug contained in the chemotherapy regimens ; for anthracycline use, ejection fraction should be > 50% * Any serious active disease (according to the investigator's decision) * History of deep venous thrombosis or arterial thromboembolism events within the past 12 months before inclusion * Poor renal function (creatinine clearance < 40 ml/min, according to Modification of Diet in Renal Disease (MDRD) formula) * Poor hepatic function (total bilirubin level >30mmol/l, transaminases >2.5 maximum normal level) unless these abnormalities are related to the lymphoma * Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration * Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score ≤7, and a prostate specific antigen (PSA) ≤10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (i.e., prostatectomy or radiotherapy) 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or <1 ng/mL if they did not undergo prostatectomy * Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study * Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy * Prior use of lenalidomide * Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide * Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide * Subjects with ≥ Grade 2 neuropathy * Adult patient under tutelage * Female of childbearing potential are excluded. (Note: Females are defined as not of childbearing potential if there is documentation of "natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy")

Study Objectives This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) pictilisib administered with letrozole or intravenous (IV) paclitaxel with and without IV bevacizumab or IV trastuzumab in participants with locally recurrent or metastatic breast cancer. The study consists of three parts. Part 1 (pictilisib will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (pictilisib will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (pictilisib will be administered in combination with letrozole). Part 1 and Part 2 consists of two stages; a dose escalation stage and a cohort-expansion stage. Conditions: Breast Cancer Intervention / Treatment: DRUG: Bevacizumab, DRUG: Pictilisib, DRUG: Letrozole, DRUG: Paclitaxel, DRUG: Trastuzumab Location: United States, Italy, Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease * Adequate organ and bone marrow function as assessed by laboratory tests * Evaluable disease or disease measurable per RECIST * Agreement to use an effective form of contraception for the duration of the study Exclusion Criteria: * History of malabsorption syndrome or other condition that would interfere with enteral absorption * Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents * Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment * Uncontrolled current illness * Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis) * Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus * Known HIV infection * New York Heart Association (NYHA) Class II or greater congestive heart failure * Active ventricular arrhythmia requiring medication * Pregnancy, lactation, or breastfeeding * Known significant hypersensitivity to study drugs or excipients * History of arterial thromboembolic disease within 6 months of first study treatment * No more than two prior chemotherapy regimens for metastatic disease

Study Objectives The purpose of this study is to determine if E7389 is a safe and effective treatment for advanced/metastatic breast cancer. Conditions: Breast Neoplasms Intervention / Treatment: DRUG: E7389 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: * Female patients with histologically or cytologically confirmed carcinoma of the breast * Patients with advanced/metastatic disease that is not amenable to curative therapy (either surgery or radiation therapy) * Patients must have measurable disease by the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one diameter (at least 10 mm in longest diameter (LD) by spiral computer tomography (CT) scan, or at least 20 mm by standard techniques; If the only measurable lesion is a lymph node, it must measure at least 20 mm in LD. If a single lesion is identified as the target lesion, a cytological or histological confirmation of breast carcinoma is required. * Patients must have had prior treatment with an anthracycline and a taxane (either sequential or in combination) and may have had prior treatment with other agents as well. * Patients must have progressed within six months of the last dose of chemotherapy, or experienced disease progression while receiving chemotherapy for advanced/metastatic disease. * Resolution of all chemotherapy or radiation-related toxicities to less than grade 1 severity * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) Performance Status (APPENDIX 4) of 0 or 1 * Life expectancy of ≥ 3 months * Adequate renal function as evidenced by serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/minute (min) per the Cockcroft and Gault formula * Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin <10.0 g/dL would be acceptable if it can be corrected by growth factor or transfusion), and platelet count ≥ 100 x 10\^9/L * Adequate liver function as evidenced by bilirubin ≤ 1.5 mg/dL and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) ≤ 3 times the upper limits of normal (ULN) (in the case of liver metastases ≤ 5 x ULN) * Patients willing and able to complete the FACT-B questionnaire, Analgesic Diary, Pain VAS, and the tumor-related symptomatic assessment * Patients willing and able to comply with the study protocol for the duration of the study * A sample from the diagnostic biopsy (paraffin block) must be available * Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice Exclusion Criteria: * Patients who have received chemotherapy, radiation, hormonal therapy, or Herceptin within 2 weeks of E7389 treatment start * Radiation therapy encompassing > 10% of marrow * Failure to recover from any chemotherapy related or other therapy related toxicity at study entry that is deemed to be clinically significant by the study investigator * Prior treatment with Mitomycin C or nitrosoureas * Prior high dose chemotherapy with hematopoietic stem cell rescue in the past two years * Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen * Active symptomatic brain metastasis; Patients with central Nervous System (CNS) metastasis are considered eligible if they have completed local therapy and discontinued from corticosteroids for at least two weeks before starting treatment with E7389 * Patients with meningeal carcinomatosis * Patients who require therapeutic anti-coagulant therapy with Warfarin or related compounds; Mini dose warfarin for catheter related thrombosis prophylaxis is permitted * Women who are pregnant or breast-feeding; Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. * Severe /uncontrolled intercurrent illness/infection * Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia) * Patients with organ allografts * Patients with known positive HIV status * Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ 5 years previously with no subsequent evidence of recurrence * Patients with pre-existing neuropathy > Grade 1 * Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative * Patients who participated in a prior E7389 clinical trial * Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study

Study Objectives 1. Advanced NSCLC has a poor prognosis and the positive impact of chemotherapy is limited by the development of intrinsic and acquired resistance. 2. Over the past decade, less toxic agents such as the innovative targeted therapies, i.e. erlotinib or gefitinib, have the potential to improve the effectiveness and keep a good quality of life with a low toxicity 3. BIBW2992 (afatinib), an aniline-quinazoline, is an epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2) irreversible inhibitor, and it has activity against erlotinib-resistant isoforms having mutations in EGFR and HER-2. 4. This molecule has shown benefits as a single agent in pre-treated patients who have progressed despite platinum-based chemotherapy, with a minimal toxicity compared to chemotherapy. 5. BIBW2992 is associated with adverse effects similar to those for erlotinib and gefitinib, such as rash and diarrhea. These symptoms can reduce the quality of life (QL) in patients and lead to inconsistent EGFR inhibitor dose administration 6. There is not a standard treatment for rash. However, case reports have tried to demonstrate the benefit in the treatment of these cutaneous injuries obtained with alcohol-free emollients, sunscreen with titanium dioxide or antibiotic (topic or oral) treatment regimens that include clindamycin or doxycycline, as well as anti-inflammatory drugs such as steroids and isotretinoin. 7. In order to reduce the incidence and severity of cutaneous toxicities, we will compare the prophylactic antibiotic treatment using tetracycline and general dermatological recommendations versus using only dermatological recommendations, in patients initiating the treatment with BIBW2992. Conditions: Skin Rash, Lung Cancer Intervention / Treatment: DRUG: Tetracycline Location: Mexico Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Diagnosis of non-operable, locally advanced, recurrent or metastatic, histologically or cytologically documented non-small cell lung cancer (stage IIIB or IV). * Patients should have an evidence of measurable disease. * 18 years or older * Eastern Cooperative Oncology Group - Performance Status 0-3 * At least 12 weeks of life expectancy * Patients with non-small cell lung cancer stages IIIB/IV who have received at least one cycle of platinum-based, first or second line systemic standard chemotherapy, and have a documented failure for this treatment. * More than 2 previous chemotherapy regimens are not allowed. The patients should have recovered from any toxic effect and at least 2 weeks should have elapsed from last dose before their entry (14 days for vinorelbine and other vinca alkaloids or gemcitabine). Patients who in the investigator's opinion are fully recovered from surgery for at least 4 weeks may also be considered for the study. Patients should have recovered from any severe toxicity (CTC > 1) caused by any previous therapy. * Granulocyte count > 1.5x 109/L and platelet count > 100x 109/L. * Serum bilirubin > 1.5 upper limit of normal (ULN) * AST and/or ALT > 2 ULN (or >5 x ULN when clearly attributable to presence of hepatic metastases). * Serum creatinine > 1.5 ULN or creatinine clearance < 60 mL/min * Capability to fulfill the study and follow-up procedures. * A negative pregnancy test should be obtained from all women of childbearing potential within 72 hours previous to therapy beginning. * Patients of reproductive potential should use effective contraceptive methods. * Written (signed) informed consent to participate in the study Exclusion Criteria: * Patients allergic to the antibiotic therapy used. * Any unsteady systemic disease (including active infection, uncontrolled hypertension, unsteady angina, congestive cardiac failure, hepatic, renal or metabolic disease). * A previous treatment using a systemic anti-tumor therapy with EGFR inhibitors (tyrosine kinase inhibitors). * Any other malignant pathology within 5 previous years (except for carcinoma in situ of cervix or basal-cell type skin cancer appropriately treated). * Patients with cerebral metastases or spinal marrow compression recently diagnosed and/or definitely surgery and/or radiation naïve-treatment patients are excluded. Those with previously diagnosed and treated metastasis to Central Nervous System (CNS) or spinal marrow compression, having an evidence of steady disease (clinically steady in imaging studies) are accepted for at least 2 months. * Any significant ophthalmologic abnormality, especially severe dry-eye syndrome, keratoconjunctivitis sicca, Sjögren's syndrome, severe exposure keratitis and any other disorder that may increase the risk for corneal epithelial injure. Contact lens use during the study is not recommended. The decision to continue to use contact lens should be discussed with the oncologist responsible for patient treatment and the ophthalmologist. * Patients who cannot take oral medication, requiring intravenous nutrition, who underwent previous surgical procedures affecting absorption, or with active peptic ulcer. * Nursing women.

Study Objectives The main purpose of this study to determine the safety of an experimental medicine called 131I-MIP-1095. 131I-MIP-1095 is an investigational drug, meaning it has not been approved by the U.S. Food \& Drug Administration (FDA). Conditions: Prostate Cancer, Metastatic Castration-Resistant Prostate Cancer (mCRPC) Intervention / Treatment: DRUG: 131I-MIP-1095 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: * Males, age ≥18 years. * Subjects must have histologically or cytologically confirmed adenocarcinoma of the prostate * Subjects must be castration resistant with evidence of progressive prostate cancer despite castrate levels of testosterone (≤ 50 ng/dL) according to the PCWG3 criteria * Subjects must have metastatic disease detectable by either bone scan or cross sectional imaging by CT or MRI as per the PCWG3 guidelines * Subjects must have progressive disease at study entry defined as 1 or more of the following 3 criteria that occurred while the subject was on androgen deprivation therapy: * PSA progression defined by a minimum of two rising PSA levels with an interval of ≥1 week between each determination. Subjects who received an anti-androgen as part of their primary hormonal therapy must demonstrate progression after withdrawal. The PSA value at screening should be ≥ 2 μg/L (2 ng/mL). * Soft tissue disease progression defined by RECIST 1.1 * Bone disease progression defined by PCWG3 with two or more new lesions on bone scan. Note: For subjects enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan performed during prior therapy. If the comparison scan is not available, the baseline scan report must reference the previous scan to document progression * Subjects who received combined androgen blockade as their first-line hormonal therapy with an antiandrogen must have shown PSA progression after discontinuing the antiandrogen for ≥ 6 weeks prior to study treatment. No washout is needed after abiraterone or enzalutamide are discontinued. First generation antiandrogens such as bicalutamide must be withdrawn if given as first-line therapy. * ECOG Performance status of 0-1. * Adequate organ reserve as evidenced by: 1. neutrophil count ≥ 1500 μL 2. platelet count ≥ 100,000/μL 3. hemoglobin ≥ 9.5 g/dL 4. total bilirubin level ≤1.5 x ULN 5. AST and ALT ≤2.5 x ULN 6. serum amylase ≤ ULN 7. lipase ≤ ULN 8. serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min (Cockroft Gault equation) 9. clearance of 99mTc MAG3 within 1.5 x ULN and no evidence of obstruction on the scan. * Serum albumin of > 3.0 g/dL * Subjects must have received, were ineligible to receive, or refused at least one cytotoxic chemotherapy and enzalutamide or abiraterone or both enzalutamide and abiraterone. * Subjects must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 30 days after the last dose of study drug. Sperm donation is prohibited during the study and for 30 days after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent. * Life expectancy ≥ 6 months Exclusion Criteria: * Subject has predominant histologically or cytologically confirmed neuroendocrine prostate cancer (mixed histology is permissible, as is positivity of serum CgA and CEA). * Subject has received an investigational therapeutic agent for prostate cancer within 4 weeks prior to the administration of 131I-MIP-1095. * Subject who has not recovered from the effects of any major surgery prior to initial treatment * Subject has received treatment with a systemic therapeutic radioisotope (89Sr, 223Ra dichloride, 153Sm-lexidronam) or has received prior external beam radiation therapy (EBRT) of the head and/or neck. * Subject is currently on renal dialysis * Subject has started treatment with denosumab < 1 month prior to study entry. Subjects are allowed to be on bisphosphonates or denosumab provided they are on a stable dose for ≥ 4 weeks before administration of study drug * Subject using chronic systemic steroids greater than the equivalent of 10 mg of prednisone/prednisolone per day in the 2 weeks preceding study entry ; replacement doses of steroids, topical, inhalational, nasal and ophthalmic steroids are permitted. * Diagnosis of other invasive malignancies within the preceding 3 years prior to screening with > 30% likelihood of relapse within the next 3 years, except non-melanoma skin cancer and non-muscle invasive urothelial cancer * Any other serious illness or medical condition or social circumstance that might interfere with the subject's participation in the trial or interfere with the interpretation of the results, including, but not limited to: 1. any uncontrolled infection 2. NYHA Class III or Class IV heart failure 3. unstable angina 4. myocardial infarction within the 6 months prior to study entry 5. uncontrolled hypertension (systolic BP > 160 mmHg despite 2 antihypertensive medications) 6. COPD requiring hospital admission in the year prior to study entry 7. diabetes mellitus requiring hospital admission in the year prior to study entry 8. chronic liver disease 9. hypothyroidism (TSH level > 3.0 mIU/L) 10. substance abuse * Unable or unwilling to follow post-therapy radiation protection procedures

Study Objectives Chronic Obstructive Pulmonary Disease \[COPD\] is a major cause of chronic morbidity and mortality worldwide. COPD is characterized by persistent progressive airflow limitation that adversely affects the ventilation/perfusion (V/Q) matching and mechanics of the respiratory muscles and leads to hypoventilation and reduced gas transfer. COPD was identified as a significant comorbidity associated with increased incidences of postoperative pulmonary complications and prolonged hospital stay. MgSO4 either intravenous or inhalational has been shown to promote bronchodilation and to improve lung function in asthmatic patients. MgSO4 either intravenous or inhalational has been shown to promote bronchodilation and to improve lung function in asthmatic patients. Administration of MgSO4 in patients with stable COPD was associated with reduced lung hyperinflation and improvement of respiratory muscle strength. This randomized control trial is designed to assess the effect of intravenous MgSO4 infusion on oxygenation and pulmonary mechanics and incidence of postoperative pulmonary complications and length of hospital stay in patients with COPD undergoing cancer larynx surgery. Conditions: Chronic Obstructive Pulmonary Diseases Intervention / Treatment: DRUG: Magnesium Sulphate Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients undergoing cancer larynx surgery (partial laryngectomy, total laryngectomy with or without neck dissection). * Age more than 40 years old * ASA physical status II and III. * Diagnosed as having COPD by preoperative spirometry. The classification is bases on the post-bronchodilators forced expiratory volume in the first second (FEV1). Mild COPD is diagnosed when FEV1 is > 80% of predicted while moderate COPD is diagnosed when FEV1 is < 80% and > 50% of predicted and sever COPD is diagnosed when FEV1 is < 50% and > 30% of predicted Exclusion Criteria: * o Patients with heart failure. * History with arrhythmias or treatment with antiarrhythmic drugs. * Patient with heart block or on beta blockers or calcium channel blockers. * Patients with impaired renal function (creatinine > 2) * Patients with impaired liver function (ALT more than 2 folds). * Patient with combined restrictive and obstructive pulmonary disease. * Patients with preoperative tracheostomy. * Patients with huge mass obstructing > 50% of the view. (due to its influence on the spirometry measurements).

Study Objectives This open-label, multicenter, phase 1b study will evaluate the safety and pharmacokinetics of DNIB0600A in participants with platinum-sensitive ovarian cancer (PSOC) or Non-Squamous Non-small Cell Lung Cancer (NSCLC). The maximum tolerated dose of intravenously infused DNIB0600A in combination with carboplatin will be determined in escalating dose cohorts. The combination of DNIB0600A and carboplatin will then be evaluated with and without bevacizumab \[Avastin\] in three dose expansion cohorts. Conditions: Non-Squamous Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: Bevacizumab, DRUG: Carboplatin, DRUG: DNIB0600A Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. * Histologically documented epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that is platinum sensitive. * PSOC (i.e., epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer) with documented radiographic progression or relapse within 6 to 18 months of most recent platinum-based chemotherapy. * Female participants of childbearing potential must use effective contraception as defined by study protocol and cannot be pregnant or breastfeeding. NSCLC-specific Inclusion Criteria: * Histological documentation of incurable, locally advanced, or metastatic non-squamous * NSCLC that has progressed on prior treatment * Not more than 2 prior regimens in the metastatic setting, including one prior cytotoxic regimen and one prior non-cytotoxic regimen (prior treatment with adjuvant therapy within 6 months of recurrence is considered a treatment regimen in the metastatic setting). * For participants with a documented epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement, one additional line of non-cytotoxic prior treatment will be permitted provided the therapy is a targeted agent against the EGFR mutation or ALK rearrangement. * For participants with lung cancer, centrally confirmed high expression of a sodium-dependent phosphate transporter (NaPi2b) by immunohistochemistry (IHC) is required (i.e., IHC 2+ or 3+). Exclusion Criteria: * Anti-tumor therapy of any kind or major surgery within 4 weeks prior to Day 1. * For ovarian cancer participants only, platinum-based chemotherapy within 6 months prior to Day 1. * For ovarian cancer participants only, platinum treatment with more than two platinum-based chemotherapy regiments or more than four anti-cancer regimens, overall, for the treatment of ovarian cancer. * Palliative radiation within 2 weeks prior to Day 1. * Toxicity (except alopecia and anorexia) from prior therapy or neuropathy of grades > 1. * Evidence of any significant disease or condition that could affect compliance with the protocol or interpretation of results. * Known active infection (except fungal nail infections). * History of liver disease or human immunodeficiency virus (HIV). * Other malignancy within the last 5 years, except for adequately treated or controlled carcinoma in situ of the cervix or skin cancer or primary endometrial cancer of stage <= 1B. * Untreated or active central nervous system (CNS) metastases. * Prior treatment with NaPi2b- targeted therapy. Bevacizumab-Specific Exclusion Criteria (for Participants in Second Ovarian Expansion Cohort Only): * Inadequately controlled hypertension or history of hypertensive crisis or encephalopathy. * History of heart problems or thrombosis within 6 months prior to study start. * History of stroke within 6 months prior to study enrollment. * History of significant vascular disease. * History of expectoration of blood within 1 month prior to study start or blood clotting problems. * Core biopsy or other minor surgical procedure within 7 days prior to study start * Serious and non-healing wound, active ulcer, or untreated bone fracture.

Study Objectives The purpose of this study is to learn whether daily use of Duavee® is accepted and tolerated by peri- and post-menopausal women at moderate risk for development of breast cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: Duavee Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Women with vasomotor symptoms with a uterus who are postmenopausal or in late menopause transition * Body Mass Index (BMI) <36 kg/m2 * Class I-III mammogram within 6 months of Random Periareolar Fine Needle Aspiration (RPFNA); If Class 0 or 4, must be resolved with additional procedures * If previously on oral contraceptives or hormone replacement, off for 8 weeks or more prior to baseline RPFNA; the exception is low dose vaginal hormones * Confirmed moderate risk of developing breast cancer * RPFNA results within study defined range * Kidney and liver function within study defined range * Willing and able to comply with study related procedures Exclusion Criteria: * Previous biopsy showing evidence of breast cancer * Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke * History of renal or liver disease * Prior ovarian or endometrial cancer * Stopped or started hormone replacement within 8 weeks * Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA * Currently taking or have taken specific medications in the past 6 months * Participation on any chemoprevention trial within 6 months * Current illness which would make potential participant unsuitable for enrollment

Study Objectives Xerostomia, or dry mouth, is a common side effect of head neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Most of these supportive interventions do not reverse xerostomia and are palliative in intent. The investigators propose that autotransplantation of marrow-derived mesenchymal stromal cells (MSCs) in salivary glands post-RT or post-chemoradiation therapy (CRT) may provide an innovative remedy to treat xerostomia and restore quality of life. Participants can expect to be on study for up to 6 months. Conditions: Xerostomia, Head and Neck Cancer Intervention / Treatment: PROCEDURE: Bone Marrow Aspiration, DIAGNOSTIC_TEST: Ultrasound Imaging of Salivary Glands, OTHER: Salivary Assay, OTHER: Quality of Life Instruments Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: BASIC_SCIENCE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Participants ≥2 years from completion of chemoradiation therapy or radiation therapy (N=6) with subjective complaint of xerostomia or with no diagnosis of HNC (N=5) * Karnofsky ≥ 60, participant eligible for bone marrow aspirate with wakeful anesthesia * Not pregnant * Willing and able to give informed consent * non-HNC participants only need to meet the following applicable inclusion criteria * No history of radiation to the salivary glands * Willing and able to give informed consent Exclusion Criteria: * Salivary gland disease (e.g., sialolithiasis)

Study Objectives The objective of this study is to evaluate the feasibility of two different chemotherapy protocols with adjusted doses for patients aged 75 and over who often have medical problems other than prostate cancer. Patient will receive Docetaxel either every 3 weeks or weekly. In both cases, chemotherapy is combined with prednisone. The protocol will be considered feasible when patient will receive 6 cycles of chemotherapy (1 cycle = 3 weeks). Additionally to this primary objective, efficacy will also be evaluated for both protocols as well as tolerance to treatment, quality of life and evolution of geriatric data. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Docetaxel every 3 weeks + Prednisone, DRUG: Docetaxel weekly+ Prednisone Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age >= 75 * Histologically proven prostate adenocarcinoma * Metastatic disease, not pre-treated with chemotherapy refractory to castration * Hormone refractory prostate cancer is defined as follows: * Patients with documented testosterone castration (<0.50 ng / ml) * Patient who received prior hormonal therapy (either orchidectomy or Luteinizing hormone-releasing hormone (LHRH) agonist alone or combined with an anti-androgen) * Patients should continue primary androgen suppression by LHRH agonist (in case of non-surgical castration) * For patients treated with anti-androgens prior to inclusion, a wash-out period is required (4 weeks for flutamide and nilutamide, 6 weeks for other products) as well as measured progression after anti-androgen discontinuation. * Progressive disease under hormonotherapy, with progression defined by Increase of PSA level (two consecutive increases of PSA compared to baseline with a minimum of one week between both measurements) OR emergence of a new lesion OR measurable progressive disease (increase of a previous measurable lesion >= 25% in cross section) OR progressive bone metastases (defined only by the appearance of a new lesion on bone scan) OR progressive symptoms (defined as cancer pain Grade 2 according to the NCI-CTC V4.0, despite level 2 analgesics intake). * Patients of Groups 2 and 3 \[ "vulnerable" and "frail"\] of SIOG classification * WHO Performance Status (PS) >= 3 * PSA >= 5 ng / ml * Neutrophils >= 2.109 /L * Platelets >= 100.109/L * Haemoglobin ≥ 9 g/dl * Bilirubin and SGOT / SGPT <1.5 x ULN (<= 2.5 x ULN if hepatic metastasis) * creatinine <= 2.5 x ULN * In case of previous palliative or analgesic radiotherapy, a minimum of 14 days must have elapsed between end of radiotherapy and inclusion into the study * Previous treatment with bisphosphonates should be continued without change during the study treatment and can not be initiated either within 28 days prior to study entry or during the study * Signed informed consent by patients, according to local regulations Exclusion Criteria: * "healthy" or "terminal illness" Groups according to the recommendations of International Society of Geriatric Oncology (SIOG) * Concomitant or previous malignancy within 5 years prior the study (except basal or squamous in situ cell skin carcinoma) * Presence of brain metastasis symptoms * Prior treatment by intravenous radiopharmaceutical agent (e.g. Strontium 89, Samarium lexidronam) within 2 months before study entry * Initiation of a bisphosphonate therapy within 28 days prior to randomisation * Any concomitant anticancer treatment (radiotherapy, radiopharmaceutical agent, chemotherapy) * Patients with uncontrolled infection * Patients with peripheral neuropathy of grade> 1 * Patients medically unstable (e.g. unstable diabetes, uncontrolled hypertension or decompensated heart failure or myocardial infarct within 3 months) * Gastro duodenal active ulcer * Hypersensitivity to study drugs * Treatment with any experimental drug within 30 days prior to or during the study * Psychological, familial, sociological or geographical location conditions which do not allow medical monitoring and compliance with study protocol. * Patients protected by the law or patients placed under protective supervision of adults

Study Objectives The purpose of the clinical trial is to identify the maximum tolerated dose of SEL24/MEN1703 and to further investigate its safety profile in patients with Acute Myeloid Leukemia. Conditions: Acute Myeloid Leukemia Intervention / Treatment: DRUG: SEL24/MEN1703 Location: United States, Italy, Spain, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * patients with diagnosis of Acute Myeloid Leukemia, all comers (completed) and bearing IDH1 or IDH2 mutation (open for recruitment) * Patient has no standard therapeutic options available and has either Relapsed AML unsuitable for intensive chemotherapy and not eligible for any approved targeted therapy or Primary refractory AML unsuitable for intensive chemotherapy and not eligible for any approved targeted therapy Exclusion Criteria: * anti-cancer treatments (including cytotoxic chemotherapy, radiotherapy, hormonal therapy, biologic, immunotherapy or investigational drugs) received within 14 days or 5 half-lives for targeted therapies (whichever is shorter) before first dose of study drug (to be supplemented)

Study Objectives This is a Phase 1, open label, multi center, multiple dose, dose escalation, safety, pharmacokinetic and pharmacodynamic study of palbociclib in combination with nab-P, in sequential cohorts of adult patients with mPDAC, with MTD expansion cohort(s). Approximately 30-60 patients are expected to be enrolled in the overall study. Conditions: Metastatic Pancreatic Ductal Adenocarcinoma Intervention / Treatment: DRUG: Palbociclib, DRUG: Nab-Paclitaxel Location: United States, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma. * Availability of a tumor tissue specimen. If no archived tumor tissue is available, then a de novo biopsy is required for patient participation. * Karnofsky Performance Status 70 or greater. * Adequate Bone Marrow, Renal, and Liver Function. Exclusion Criteria: * Prior treatment with a CDK 4/6 inhibitor. * Prior treatment with nab-P for the treatment of metastatic disease. * Patients with known CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. * Diagnosis of any other malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. * QTc >480 msec, or family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes. * Uncontrolled electrolyte disorders. * Cardiac or pulmonary disorders within 6 months of enrollment. * Known human immunodeficiency virus infection. * History of interstitial lung disease or pneumonitis. * Other severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-P. * Difficulty swallowing capsules or requirement for a feeding tube. * Previous high-dose chemotherapy requiring stem cell rescue. * Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant. * Active inflammatory or other gastrointestinal disease, * Active bleeding disorder in the past 6 months. * Patients treated within the last 7 days prior to the start of IP with strong/moderate CYP3A4 inhibitors, strong/moderate CYP3A4 inducers, CYP2C8 inhibitors, strong/moderate CYP2C8 inducers, or drugs that are known to prolong the QT interval.

Study Objectives The purpose of this phase II trial is to determine the efficacy and safety of the combination of oxaliplatin, capecitabine and radiotherapy as preoperative therapy in locally advanced cancers of the rectum. Conditions: Rectal Neoplasms Intervention / Treatment: DRUG: Oxaliplatin, DRUG: Capecitabine, RADIATION: Radiotherapy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * ECOG performance status score 0-1. * Chemo-naïve patients. * Histologically/cytologically confirmed diagnosis of rectal adenocarcinoma (clinically stage mT3 or mT4), either considered (1)inoperable, or (2)locally advanced, where histologically confirmed curative resection is considered unlikely. * Evaluable measurable disease on imaging with MRI/CT to allow for response assessment. * Adequate haematological, renal and liver functions as follows: * ANC > 3000ml * Platelet count > 100,000 ml * Urea \& Serum Creatinine < 1.5 X upper limit of normal value * Total serum bilirubin < 1.5 X upper limit of normal value * ALT \& AST < 3 X upper limit of normal value Exclusion Criteria: * Prior chemotherapy. * Documented allergy to oxaliplatin or capecitabine. * Prior radiotherapy to pelvis. * Previous or concurrent malignancies at other sites with the exception of basal or squamous cell carcinoma of the skin. * Pregnant or lactating females (with negative pregnancy test documentation in pre-menopausal female patients). * Currently participating into another clinical trial with any investigational drug in the previous 30 days. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Objectives This is a Phase III open-labed, multicenter, prospective, randomised study, and comparative 3-arms of 140 patients (i.e. 420 total patients). Study period (date of first inclusion/last inclusion): 3 years Treatment period : 3 months Conditions: Cancer Intervention / Treatment: DRUG: warfarine - low molecular heparin Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * First line chemotherapy for solid tumor with: * Metastatic disease or * Involved nodes or * Unresectable tumor * Indication for Implantable device for central venous access * Potential survival > 3 months * ECOG performance status 0 to 2 (WHO) * Age between 18 and 75 years. * Social security guaranteed * Normal laboratory assessments (platelets> 100000/mm3, TP 60%, spontaneous TCA with M/T<1.5, TGO and TGP < 2xN, serum creatinin<120µmol/l) * Informed consent signed Exclusion Criteria: * Inability to understand informed consent or interfering with compliance for treatment or protocol Anti-coagulant treatment -related criteria * Acute infectious endocarditis * History related with heparin allergy or thrombopenia due to heparin * Uncontrolled high blood pressure (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg) * Hemorrhagic syndrome ongoing * Patient with platelet inhibitors treatment * Chronic, daily treatment with anti-coagulant therapy (LMWH or AVK), use as preventive or curative level * Patient with liver failure (TP<60%) or renal insufficiency (creatinin clearance< 20 ml/mn) * Women with pregnancy and lactating Pathology-related criteria * deep venous thrombosis history or pulmonary embolism (< 6 months) * Clinical suspicious of brain metastasis

Study Objectives This is an open-label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D/D2). Conditions: Esophageal Cancer Intervention / Treatment: DRUG: Durvalumab, DRUG: Tremelimumab, DRUG: Oxaliplatin, DRUG: Capecitabine, RADIATION: Radiotherapy, DRUG: Paclitaxel, DRUG: Carboplatin, DRUG: 5-fluorouracil (5-FU), DRUG: Leucovorin, DRUG: Docetaxel Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histological diagnosis of oesophageal or gastrooesophageal cancer and have not received prior chemotherapy. * Cohorts A and B - metastatic/locally advanced cancer * Cohorts C/C-FLOT and D/D2 - deemed suitable for surgery with curative intent * Anticipated lifespan greater than 4 months. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and: * at least 8 weeks without tumour progression after any whole brain radiotherapy * at least 4 weeks since craniotomy and resection or stereotactic radiosurgery * at least 3 weeks without new brain metastases as evidenced by MRI/CT * Adequate normal organ and marrow function. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted. * Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements. * Age 18 years or older. Exclusion Criteria * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study. * Participation in another clinical study with an investigational product during the last 4 weeks. * Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction. * Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). * History of allogeneic organ transplant. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. * Known history of previous clinical diagnosis of tuberculosis. * History of pneumonitis or interstitial lung disease.

Study Objectives HS-10342 is a small molecular, oral potent, selective CDK4/6 inhibitor. The purpose of this study is to investigate the safety/tolerability and the pharmacokinetic profile of HS-10342 in Chinese advanced solid tumor patients. Preliminary efficacy will be also investigated in this study. Conditions: Advanced Solid Tumor Intervention / Treatment: DRUG: HS-10342 Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: 1. Pathologically confirmed solid tumor and failed from all standard treatment. 2. At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. 3. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1. 4. Life expectancy ≥ 3 months. 5. Adequate function of major organs meets the following requirements: * Neutrophils ≥ 1.5×10\^9/L * Platelets ≥ 90×10\^9/L * Hemoglobin ≥ 90g/L * Total bilirubin≤ 1.5 × the upper limit of normal (ULN) * ALT and AST ≤ 2.5 × ULN * Cr ≤ 1.5 × ULN * Left ventricular ejection fraction (LVEF) ≥ 40% 6. Good compliance of patient by physician's judgement. 7. . Signed and dated informed consent. Exclusion Criteria: * Subjects who meet any of the following exclusion criteria are not to be enrolled in this study: 1. Previously received therapy of anti-tumor agent targeting at CDK4/6. 2. Less than 3 weeks from the last cell-toxicity chemotherapy, less than 6 weeks from last mitomycin or nitrosamine therapy 3. Less than 3 weeks from any other anti-tumor therapy (including targets therapy, immunotherapy or other approved therapy) 4. Less than 4 weeks from large area radiotherapy. 5. Less than 7 days from any CYP3A4 strong inhibitor, strong inducer or a narrow window of medicine or food for CYP3A4 sensitive substrate. 6. Having joined in other clinical trials within 4 weeks. 7. Brain metastasis (well-controlled/well-treated brain metastasis by physician's judgement is allowed). 8. Existing abnormal CTCAE≥grade 2 resulted from previous treatment(except grade 2 alopecia). 9. Uncontrollable pleural effusion or ascites. 10. Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug. 11. History of serious allergy events or known being allergy constitution, or have a history of allergies to the drug components of this regimen. 12. Patients with active infection. 13. History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation. 14. History of uncontrollable cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or require drug intervention (3)myocardial infarction Less than 6 moths (4) other cardiac dysfunction (judged by the physician), such as any degree of heart block or QTc prolongation, QT interval corrected by Fridericia method(QTcF) >450 ms(men) or >470 ms(women); (5)any cardiac or nephric abnormal ≥ grade 2 found in screening. 15. Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study. 16. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study. 17. History of neuropathy or dysphrenia, including epilepsy and dementia 18. Determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment.

Study Objectives Tamoxifen and aromatase inhibitors are two oral hormonal therapies (OHT) that decrease the risk of breast cancer recurrence by over 30 %. Their efficacy however strongly depends on the duration of use (5 to 10 years). Earlier work demonstrated that the longer an individual is not taking her OHT the less likely she is to restart her therapy. Thus, identifying the moment of treatment interruption in real-time and being able to contact the patient at these specific time-points may be the key to effective health interventions by improving medication adherence to reduce BC recurrence - therefore, increasing overall Breast Cancer survival (BCS). EHealth technologies may be a very effective mean to identify these interruptions in a real-time manner and to provide support at the time the person needs it. The overall aim of the E-dherence Pilot study is to evaluate the feasibility of the E-Health intervention to enhance OHT adherence in BCS. Feasibility is defined based on 1.The eHealth intervention acceptability, 2. eHealth intervention quality and 3. medication adherence. The study will include female breast cancer starting their first prescription of tamoxifen or aromatase inhibitors and are outpatient and followed-up in either of the 2 study sites. Participants should be 18 years or older and be fluent in french and or German and possess a smart-phone (iOS, Android). The investigators exclude males, patients with in situ metastatic tumors, inpatients and non Luxembourg residents. Within the E-dherence Pilot study each patient receives the eHealth intervention. The eHealth intervention consists a Medication Event Monitoring Systems (MEMS®) Helping Hand and MEMS Adherence Software application. The eHealth intervention will support BCS to adhere to the recommended OHT (i) by alerting the participants to take their OHT, and (ii) by allowing patient-physician communication. The intervention consists of a Medication Event Monitoring Systems (MEMS®), an electronic pillbox that counts the OHT intake, the date and time. Through Near Field Communication (NFC) the device is connected to the MEMS Adherence Software application on the patients' phone (Android or iOS). At the beginning, each patient can personalize the application. This application registers the history of OHT adherence (time and date of medication intake) and sends reminders to the patient to take the treatment as scheduled. Additionally, the patient receives an integrated calendar in the App that notifies the patient for upcoming medical visits. The eHealth intervention comprises a questionnaire that should be filled-out weekly and that informs about the presence and severity of side effects. These data are collected in real-time and monitored on a weekly basis by the clinical research nurse (CRN) in charge of the study. In case of an alert, meaning recurrent non-adherence and/or reporting of side-effects, the CRN will contact the breast cancer nurse (BCN) in charge of the patient. Thus the BCN will contact the patient by phone to check on their health status and together define the future procedure in order for the patient to remain on OHT and/or to better manage their side-effects. In a worst case scenario, the BCN will refer the patient to see the emergency department and/or the oncologist. The study received all ethical approvals. Conditions: Breast Cancer Intervention / Treatment: BEHAVIORAL: Medication adherence eHealth intervention Location: Luxembourg Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Female aged ≥18 years old * 1st prescription of adjuvant treatment (Nolvadex, Arimidex) * Treated in either the Centre Hospitalier du Luxembourg (CHL) or Centre Hospitalier Emile Mayrisch (CHEM) * Luxembourg resident * Fluent in French and/or German * Outpatient * Possession of a smart-phone (iOS, Android) Exclusion Criteria: * Male * In situ or metastatic tumors * Follow-up treatment outside of CHL or CHEM * Non-Luxembourgish residents * Inpatient

Study Objectives Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with a monoclonal antibody may kill more tumor cells. This randomized phase II/III trial is to see if combination chemotherapy works better with or without bevacizumab in treating patients who have advanced, metastatic, or recurrent non-small cell lung cance Conditions: Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer Intervention / Treatment: DRUG: paclitaxel, DRUG: carboplatin, BIOLOGICAL: bevacizumab, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients must have histologically or cytologically confirmed non-small cell lung cancer EXCEPT squamous cell carcinoma; mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible; cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy * Patients must have advanced NSCLC (stage IIIB with malignant pleural effusion or stage IV or recurrent disease) * Patients must have measurable or non-measurable disease * ECOG performance status 0 or 1 * Patients must not have known central nervous system (CNS) metastases; a head CT is required within 4 weeks prior to study entry; (MRIs are also acceptable) * Patients must not have received prior systemic chemotherapy at any time * ANC >= 1500/mm\^3 * Platelets >= 100,000/mm\^3 * Total bilirubin =< 1.5 mg/dl * Transaminases =< 5 x ULN * Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) * Urine dipstick for proteinuria of less than 1+ (i.e., either 0 or trace); if urine dipstick is >= 1+ then a 24 hour urine for protein must demonstrate < 500 mg of protein in 24 hours to allow participation in the study; note: urinalysis is also acceptable * Patients must have INR =< 1.5 and a PTT no greater than upper limits of normal within 1 week prior to randomization * Pregnant and lactating women are excluded from the study * Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study * Patients must not have had immuno, hormonal or radiation therapy within 3 weeks prior to entering the study; those who have not recovered from adverse events due to agents administered more than 3 weeks earlier are ineligible * Patients must not have 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 must have no history of thrombotic or hemorrhagic disorders * Patients with history of hypertension must be well-controlled (< 150/100) on a stable regimen of anti-hypertensive therapy * Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed * Patients must not have serious non-healing wound ulcer, or bone fracture, or major surgical procedure within 21 days prior to starting treatment * Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation of venous access devices is allowed; caution should be taken on treating patients with low dose heparin or low molecular weight heparin for DVT prophylaxis during treatment with bevacizumab as there may be an increased risk of bleeding * Patients with a history of gross hemoptysis (defined as bright red blood of a 1/2 teaspoon or more) will be excluded from this trial

Study Objectives This phase II study will test cancer to see if it has a HER2 mutation and, if so, see how HER2 mutated cancer responds to treatment with neratinib. Conditions: Breast Neoplasms Intervention / Treatment: DRUG: Neratinib, DRUG: Fulvestrant, DRUG: Trastuzumab, PROCEDURE: Tumor biopsy, PROCEDURE: Research blood sample Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria for Pre-registration (for patients with unknown HER2 mutation status to have tumor tissue screened centrally by Washington University GPS laboratory): * Histologically or cytologically confirmed HER2-negative (0 or 1+ by IHC or non-amplified by FISH) breast cancer that is stage IV. * Agree to provide archival tumor material for research * There is no limitation on the number of prior lines of systemic therapy. * Presence of measurable or non-measurable disease by RECIST 1.1 is acceptable, except to be eligible for the Part II fulvestrant-naive ER+ cohort, at least one measurable disease by RECIST 1.1 is required. * At least 18 years of age. * ECOG performance status ≤ 2 * Adequate organ function as defined below within 8 weeks of pre-registration: * Serum creatinine ≤1.5 x ULN * Chil-Pugh class A if with liver disease * Able to understand and willing to sign an IRB approved written informed consent document. Note: HER2 mutation testing may be performed while the patient is receiving active systemic therapy for metastatic breast cancer so that the result can be used to determine eligibility for study drug therapy in the future. Exclusion Criteria for Pre-registration: * Testing for LVEF is not required for pre-registration, but patient must not have a recent LVEF < LLN or have symptoms of congestive heart failure. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Acute or currently active hepatic or biliary disease requiring antiviral therapy (with the exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment). * History of significant cardiac disease, cardiac risk factors, or uncontrolled arrhythmias. * Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest. Inclusion Criteria for Registration (for patients initially pre-registered and with HER2 mutation identified by Washington University GPS laboratory) * Tumor tissue tested positive for HER2 mutation. HER2 mutations detected by Guardant360 are also eligible. * Agree to provide archival tumor material for research * ECOG performance status ≤2 * Adequate organ function as defined below within 2 weeks of registration: * ANC ≥1.5 x 10\^9/L * Platelet count ≥100 x 10\^9/L * Serum creatinine ≤1.5 x ULN * Child-Pugh class A if with liver disease * The patient must have completed radiation therapy and be at least 1 week from the last systemic chemotherapy administration, with adequate recovery of bone marrow and organ functions, before starting neratinib. * Presence of disease progression on the most recent disease evaluation. * Patients with known brain metastasis are eligible, but must have received radiation and be off steroids and stable (without evidence of disease progression by imaging or exam) for 3 months. * QTc interval ≤450 msec for men or < or ≤ 470 msec for women within 2 weeks of registration. * LVEF > or = institutional ILLN within 4 weeks of registration. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of the investigational product. * Able to understand and willing to sign an IRB approved written informed consent document. * There is no limitation on the number of prior lines of systemic therapy. * To be eligible for the Part II fulvestrant-naive ER+ cohort, prior treatment with fulvestrant is not allowed. In addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required. * To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required. In addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology form an earlier time point could be used and a discussion with the study chair is required. Inclusion Criteria for Registration (for patients with HER2 mutation identified at an outside CLIA certified location): * Histologically or cytologically confirmed HER2-negative (0 or 1+ by IHC or non-amplified by FISH) breast cancer that is stage IV. * Tumor tissue or circulating tumor DNA tested positive for HER2 mutation. Mutations outside the list will be assessed on a case-by-case basis by the study team to determine eligibility. * Presence of measurable or non-measurable disease by RECIST 1.1 is acceptable, except to be eligible for the Part II fulvestrant-naïve ER+ cohort, at least one measurable disease by RECIST 1.1 is required. * At least 18 years of age. * ECOG performance status < 2 (see Appendix A). * Adequate organ function as defined below within 2 weeks of registration: * Absolute neutrophil count: ≥1.5 × 109/L (1500/mm3) * Platelet count: ≥100 × 109/L (100,000/mm3) * Serum creatinine: ≤1.5 x ULN * Child-Pugh class A if with liver disease * The patient must have completed radiation therapy and be at least 1 week from the last systemic therapy administration, with adequate recovery of bone marrow and organ functions, before starting neratinib. * Presence of disease progression on the most recent disease evaluation. * Patients with known treated brain metastasis are eligible, but must have received radiation and be off steroids and stable (without evidence of disease progression by imaging or exam) for 3 months. * QTc interval ≤ 450 msec for men or ≤ 470 msec for women within 2 weeks of registration. * LVEF > institutional LLN within 4 weeks of registration. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of the investigational product * Able to understand and willing to sign an IRB approved written informed consent document. * There is no limitation on the number of prior lines of systemic therapy. * To be eligible for the Part II fulvestrant-naïve ER+ cohort, prior treatment with fulvestrant is not allowed. In addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen if biopsy was done unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required. * To be eligible for the Part II fulvestrant-treated ER+ cohort, prior disease progression on fulvestrant is required. In addition, ER and/or PR positivity by institutional standard is required on pathology from the most recent tumor specimen unless the tissue source (for example, pleural effusion or ascites or bone biopsy) may yield false negative ER and/or PR result, in which case the pathology from an earlier time point could be used and a discussion with the study chair is required. Exclusion Criteria for Registration: * Currently receiving any other investigational agents or systemic cancer therapy. * Currently taking medications and herbal or dietary supplements that are strong cytochrome P450 (CYP) 3A4 inducers or inhibitors. The washout period must have been completed prior to the start of neratinib if the patient was taking any of these agents. If unavoidable, patients taking CYP3A4 inhibitors should be monitored closely. * 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. * Acute or currently active/requiring antiviral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment). * Pregnant and/or breastfeeding. * History of significant cardiac disease, cardiac risk factors, or uncontrolled arrhythmias. * Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest. * Experiencing grade 2 or greater diarrhea. * Prior treatment with neratinib * Child-Pugh class B or C liver dysfunction

Study Objectives This is a phase I trial of nimotuzumab that will be conducted in patients with advanced incurable solid tumors. This is a dose-seeking study to determine the maximum tolerated and recommended phase II doses of nimotuzumab that can be safely given to patients with advanced and/or metastatic solid tumors. Conditions: Advanced and/or Metastatic Solid Tumours Intervention / Treatment: DRUG: Nimotuzumab (TheraCIM h-R3) Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Advanced and/or metastatic solid tumors, refractory to standard curative therapy, or for which no curative therapy exists. * Clinically or radiologically documented disease. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. * Archival tumor specimens evaluable for expression of the EGFR (but EGFR positivity is not a requirement for study entry). * Patients must have tumor lesions accessible for biopsy for correlative studies. In cases where there are medical contraindications to tumor biopsies, exceptions may be made upon discussion with the Principal Investigators. * Age > 18 years. * ECOG performance status of 0,1,2. * Previous therapy: Previous chemotherapy, hormonal therapy, radiation and/or surgery is permitted with certain restrictions as outlined in the protocol. * Hematology and chemistry lab results within specifications outlined in the protocol. * Willingness to give written informed consent. * Patients must be accessible for treatment and follow-up. * Protocol treatment is to begin within 2 working days of patient registration. Exclusion Criteria: * Pregnant or lactating women. Both men and women enrolled on study should be using adequate birth control measures throughout the course of the study. * History of second malignancy who have a disease-free interval of less than two years (except cervical cancer in situ or nonmelanomatous skin cancer). * Untreated brain or meningeal metastases. Patients with treated and stable brain metastases are eligible providing that they have radiologic evidence of disease stabilisation of at least 3 months duration and are asymptomatic. * Untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction. * Active or uncontrolled infections, or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. * Prior therapy with EGFR targeting therapies, including monoclonal antibodies or small molecule tyrosine kinase inhibitors. * Allergy to the antibody. * Concurrent treatment with other experimental drugs or anti-cancer therapy. * Inability or unwillingness to give written, informed consent prior to study participation.

Study Objectives The purpose of this phase I study is to investigate the combination of hypomethylating agents with experimental peptide vaccination against four selected tumor antigens, known to be upregulated in response to hypomethylating agents, in patients with high risk myelodysplastic syndrome and acute myeloid leukemia. Conditions: Myelodysplastic Syndrome, Acute Myeloid Leukemia Intervention / Treatment: BIOLOGICAL: NPMW-peptide vaccine, DRUG: Azacitidine Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Participants must have received 6 courses of azacitidine and been evaluated with response to treatment. * Histologically confirmed high-risk MDS or AML (<30% blasts) and a normo- or hypercellular marrow after 6 courses of azacitidine. * Indication for continued treatment with azacitidine. * Age >18 years. * Signed consent form after receiving both written and oral information. * The patients must be willing to follow the scheduled treatment and sampling. Exclusion Criteria: * Hypocellular bone marrow after 6 courses of azacitidine. * Additional active cancer disease. Participants treated for a second malignancy may be included if the patient is without evidence of disease at least 2 years after completion of treatment. * Participants with a known hypersensitivity to any of the active substances or to any of the excipients. * Participants with secondary MDS or AML * Severe allergies or previous anaphylactic reactions. * Active autoimmune disease, for example autoimmune neutropenia/ thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, Sjögren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addison's disease, Hashimoto's thyroiditis, Grave's disease. * Concomitant treatment with systemic immunosuppressive medications (including prednisone, methotrexate etc.). Participants are allowed to receive up to 10 mg prednisone at the days of azacitidine injection. * Concomitant treatment with other experimental drugs. * Concomitant treatment with other systemic anti-cancer therapy. * Pregnant or breastfeeding females.

Study Objectives The purpose of this study is to determine the safety and tolerability of the drug SOR-C13 when given as an intravenous infusion in patients with ovarian cancer or other cancers known to over express the TRPV6 calcium channel. Conditions: Cancer Intervention / Treatment: DRUG: SOR-C13 Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria * Males and females ≥ 18 years of age * Subjects with a histologic diagnosis of solid tumor cancers of epithelial origin. * Subjects with advanced refractory cancer for which standard curative or palliative measures do not exist or are no longer effective. There is no limitation on the number or types of prior therapy. * Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment. * ECOG (Eastern Cooperative Oncology Group) Performance Score ≤ 1. * Life expectancy of greater than 12 weeks. * Subjects must have adequate organ and marrow function as defined below: 1. hemoglobin ≥9.0 g/dL (≥5.6 mmol/L) 2. white blood cells ≥3,000/mm³(≥3×10⁹/L) 3. absolute neutrophil count ≥1,500/mm³ (≥1.5×10⁹/L) 4. platelets ≥100,000/μL (≥100×10⁹/L) 5. total bilirubin ≤1.5× upper limit of normal(ULN) 6. AST/ALT/AP ≤2.5× ULN (ALT/AST ≤5.0x ULN in case of documented liver metastases 7. creatinine ≤1.5× ULN 8. albumin ≥3.0 g/dL (≥30 g/L) 9. INR ≤1.4 * Ability to understand and voluntarily sign the informed consent document Exclusion Criteria: * Chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy will not be allowed within either 30 days, or 5 half lives (whichever is longer) prior to study drug administration. * History or clinical evidence of central nervous system (CNS) tumor involvement (metastases) or other known clinically relevant CNS pathology (e.g., epilepsy, seizure, paresis, aphasia, cerebellar disease, severe brain injury, psychosis). * Concurrent malignancy other than the solid tumor under investigation, requiring active treatment. * History of clinically significant allergic reaction attributed to any injected compound. * History of any of the following cardiovascular events or conditions within the past 6 months prior to enrolment: myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, New York Heart Association Class ≥ II chronic heart failure, hypokalemia, significant arrhythmia\*; QTc interval >430 msec or use of drugs that prolong the QT interval at screening; family history of long QT syndrome.(\* Significant arrhythmias are defined as symptoms of syncope or severe palpitations (palpitations requiring referral to cardiac monitoring), or ECG findings of supraventricular tachycardia (including ventricular fibrillation) or ventricular ectopy (ventricular premature depolarization). * Clinically significant and uncontrolled major medical condition(s) that places the subject at an unacceptably high risk for toxicities. These include, but are not limited to: active infections, symptomatic pulmonary disease, inadequate pulmonary function, seizure disorder, psychiatric illness. * Current use of more than one antihypertensive medication. * For patients receiving antihypertensive medication:systolic blood pressure < 120 mmHg and/or diastolic blood pressure < 70 mmHg at screening. * A known diagnosis of human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS), acute or chronic hepatitis B or hepatitis C infection, as determined by medical history. * Major surgical procedure within 4 weeks prior to enrolment. * Lactating or pregnant female. * Females of childbearing potential and males not using adequate birth control. * Current treatment or treatment within 4 weeks of screening with bisphosphonates. * Screening serum calcium levels < 2.20 mmol/L \[8.8 mg/dL\] (after correction for serum albumin * History of acute pancreatitis within 12 months prior to screening * Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or clinical evidence of other conditions known to associated with hypocalcemia, including:, hypoalbuminemia, hyperphosphatemia, hypomagnesemia * Current treatment or treatment within 4 weeks of screening with drugs known to reduce serum calcium levels, including: bisphosphonates, antiepileptic drugs, cinacalcet, macrolide antibiotics (such as erythromycin, azithromycin), large doses of corticosteroids (>20 mg/day of prednisone or equivalent), or any IV use of corticosteroids. In addition, long-term use (defined as ongoing use for ≥4 weeks) of corticosteroids within 8 weeks of screening is prohibited * Any history of a venous thromboembolic event (VTE), including deep vein thrombosis (DVT) or pulmonary embolism (PE) * Current treatment or treatment within 7 days of screening with a vitamin K antagonist, such as warfarin. Patients who require anticoagulation due to their central line may receive an alternative agent, such as low molecular weight heparin (LMWH).

Study Objectives Recently, European Medicines Agency approved ibrutinib and idelalisib to treat Chronic Lymphocytic Leukemia (CLL) and two lymphomas: Follicular Lymphoma (FL) for ibrutinib and Mantle cell lymphoma (MCL) for idelalisib. Clinical trials for ibrutinib and idelalisib were performed with a small number of patients (300-350) and showed several side effects profiles. Since, pharmacokinetic properties of these 2 drugs highlight a interindividual variability of pharmacokinetic. The aim of this study is to determine the association between clinically significant side effects occurrence during the first year of treatment and plasma mean concentration of the steady state of ibrutinib or idelalisib at 1 month. Conditions: Hematological Malignancies Intervention / Treatment: OTHER: Blood samples for pharmacokinetics exploration, OTHER: Imagery, OTHER: Quality of life scale, OTHER: Detection of adverse events, GENETIC: Saliva samples, GENETIC: Blood sample, OTHER: Biological statement, OTHER: Clinical examination Location: France Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Evidence of Chronic Lymphocytic Leukaemia (CLL), or Follicular Lymphoma (FL) or Mantle cell lymphoma (MCL) and a first prescription of idelalisib or ibrutinib * Patients must give written informed consent * Patients with Health Insurance System Exclusion Criteria: * Patient who several blood tests can't be performed (poor venous access) * Patients under legal guardian * Pregnant or breastfeeding women

Study Objectives The primary objective of this sub study is to evaluate the efficacy of the combination of TSR-042, bevacizumab, and niraparib in participants with advanced, relapsed, high-grade ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 2 prior lines of anticancer therapy, are PARP inhibitor naïve, and have platinum-resistant but not refractory disease. This study is a sub study of the master protocol - OPAL (NCT03574779). Conditions: Ovarian Neoplasm Intervention / Treatment: DRUG: Dostarlimab, DRUG: Bevacizumab, DRUG: Niraparib 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: * Participant must be resistant to the most recent platinum-based therapy, defined for the purpose of this protocol as progression within 6 months from completion of a minimum of 4 cycles of platinum-containing therapy. This should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing disease progression. Participant with primary platinum-refractory disease as defined by those who progressed during or within 4 weeks of completion of first platinum-based chemotherapy are not eligible * Participant must not have received any prior therapy for ovarian cancer with a PARP inhibitor * Participant has had 1 to 2 prior lines of anticancer therapy for ovarian cancer * Participant is able to take oral medications. Exclusion Criteria: * Participant has known hypersensitivity to TSR-042, bevacizumab, niraparib, their components, or their excipients * Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia * Participant has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Participant received prior treatment with an anti- programmed death-1 (PD-1) or anti- programmed death-ligand 1 (PD-L1) agent * Participant has received prior treatment with anti-angiogenic therapy with the exception of bevacizumab. (Participant who received prior bevacizumab are eligible only if they did not discontinue bevacizumab due to toxicity, as established by the Investigator.) * Participant has bowel obstruction, had bowel obstruction within the past 3 months, or is otherwise judged by the Investigator to be at high risk for bowel obstruction related to the underlying disease. Participant has any history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or significant bowel involvement on computed tomography scan * Participant has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (Participant discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2g of protein in 24 hours to be eligible.) * Participant is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months) * Participant has a history of recent major thromboembolic event defined as follows: 1. Pulmonary embolism diagnosed within 3 months of enrollment 2. Lower extremity deep venous thrombosis diagnosed within 3 months of enrollment (Participant with a history of thromboembolic disease on stable therapeutic anticoagulation for more than 3 months prior to enrollment are eligible for this study.)

Study Objectives This protocol corresponds to a multicenter, open-label, non-randomized, phase I study designed to determine the safety of the combination of selinexor with chemotherapy in young patients with relapsed or refractory AML. The clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles) and follow-up periods and consists of a phase I design in which es-calating doses of selinexor will be given to 3 groups, each with 3-6 patients until achieving the maximum tolerated dose (MTD). Conditions: Acute Myeloid Leukemia Intervention / Treatment: DRUG: Selinexor, DRUG: fludarabine, DRUG: idarubicin, DRUG: cytarabine, DRUG: G-CSF Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. * Age ≥ 18, and ≤ 65 years old. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Diagnosis of AML (defined using WHO criteria) of any type except for acute promyelocytic leukemia (APL; AML M3). * Relapsing or refractory AML, defined as either: Recurrence of disease after first CR (duration of CR ≤ 24 months), or Failure to achieve CR or CRi after 1 or 2 identical induction cycles containing an anthracycline plus cytarabine based schedule. * No contraindications to receive intensive chemotherapy. * Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use two reliable methods of contraception for three months after their last dose of medication. Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential). * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures. Exclusion Criteria: * Patients with APL/AML M3. * Patients who are pregnant or lactating. * Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Hydroxyurea is permitted until 1 day prior to Cycle 1 Day 1. * Previous treatment with a SINE compound. * Major surgery within 2 weeks of first dose of study drug. * Any life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety. * Unstable cardiovascular function: * Symptomatic ischemia, or uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or congestive heart failure (CHF) of NYHA Class ≥ 3, or myocardial infarction (MI) within 3 months. * Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral. * Active hepatitis B or hepatitis C infection. * Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study). * Patients unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment. * Any of the following laboratory abnormalities unless due to leukemia: * Hepatic dysfunction: bilirubin > 2.0 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome: total bilirubin of > 3 x ULN) and alanine aminotransferase (ALT) and aspartic aminotransferase (AST) > 2.5 times ULN or in case of liver metastases: In patients with known liver involvement of their cancer, AST and ALT > 5 x ULN. * Severe renal dysfunction: estimated creatinine clearance of < 30 mL/min, measured in 24 hour urine or calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/\[72 x creatinine (mg/dL)\]; multiply by 0.85 if female

Study Objectives This study is designed to evaluate the safety and efficacy of a single injection of NX-1207 for the treatment of biopsy-confirmed low risk localized (T1c) prostate cancer in patients currently undergoing active surveillance. Study participants currently on active surveillance will be randomized either to treatment with a single intraprostatic injection of NX-1207 (2.5 mg or 15 mg) followed by active surveillance or to no treatment (continued active surveillance). Blinded efficacy evaluation will be by a second post-treatment prostate biopsy. Conditions: Prostate Cancer Intervention / Treatment: DRUG: NX-1207 2.5 mg, DRUG: NX-1207 15 mg Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * T1c prostate cancer * Gleason score ≤ 6 with no Gleason pattern of 4 or 5. * Life expectancy ≥ 5 years. * Single positive prostate biopsy core with ≤ 50% cancer * PSA ≤ 10 ng/mL Exclusion Criteria: * Previous active treatment (such as surgery, brachytherapy, radiotherapy) for prostate cancer. * Evidence of metastatic disease or previous positive bone scan. * Previous hormonal therapy for prostate cancer. * Use of certain concomitant medications, including 5 alpha reductase inhibitors (e.g. finasteride, dutasteride), androgen receptor blockers (e.g. flutamide, bicalutamide), immunosuppressants(such as Imuran™, Enbrel™, Remicade™, Humira™, etc.), anticoagulants(such as Coumadin™ or heparin), or chemotherapeutics. * Previous surgical or invasive prostate treatments such as TURP, TUMT, TUNA, laser or any other minimally invasive treatment within the past 12 months. * Pelvic irradiation. * Urinary tract infection more than once in the past 12 months. * Acute or chronic prostatitis in the past 12 months. * Clinically significant renal or hepatic impairment. * Bleeding disorder. * Poorly controlled diabetes type 1 or type 2. * Urinary retention in the previous 12 months. * Self-catheterization for urinary retention. * Post-void residual urine volume > 200 mL. * Prior significant rectal surgery or any rectal condition with rectal stenosis or fistula. * History of alcohol or substance abuse or dependence within the past 2 years.

Study Objectives Background: Head and neck cancer patients are in high risk to suffer from malnourishment, a risk that increase in postoperative condition and with the use of enteral nutrition (EN). Until now patients who are suffering from indigestion in the ICU received treatment in the form of prokinetic drugs, drags that can lead to serious side effects and only can partially improve digestion. Acupuncture was used successfully in several clinical trials to improve postoperative indigestion in cancer patients without any reported adverse events. This study aims is to design a double blind settings in order to investigate acupuncture effect in combination of prokinetic drugs in the prevention of indigestion in postoperative oral and hypo-pharyngeal cancer patients in the Intensive Care Unit (ICU). Methods: Single center, double blind randomize control trial will compare between two equal groups. A total of 28 patients that will meet the inclusion criteria: Age 30-80, Post plastic surgery for oral cancer or hypo-pharyngeal cancer, Apache score below 20 needed EN. Patients will be randomly divided into specific acupuncture (ACU) or non-specific acupuncture (CON) for 3 treatments in 3 days by a blind acupuncturist along with prokinetic drugs. The main outcome measurement will be the amount of days a patient need to reach Total Energy Expenditure (TEE). Expected outcome: The results will shed light on the effectiveness and safety of acupuncture in a double blind design for posts-surgery ICU cancer patients. In addition, the study presents a revolutionary double blind design that if will prove as successful might influence the way double blind acupuncture studies are performed today. Conditions: Oral Cancer, Hypopharyngeal Cancer Intervention / Treatment: OTHER: Specific acupuncture group, DRUG: Metoclopramide 10mg, OTHER: Non-specific acupuncture group Location: Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Age 30-80 * Apache score below 20 * Patients needed EN * Post plastic surgery, including oral cancer or hypo-pharyngeal cancer Exclusion Criteria: * Coagulopathy, * prolong prothrombin time (PPT) activated partial thromboplastin time (aPTT) more then 4 times * Thrombocytopenia - low platelet count * Clinically unstable: receiving two inotropic agents or Fraction of inspired Oxygen (FiO2) >70% * Estimated ICU stay - less than 3 days

Study Objectives To assess the safety and efficacy of PF-00299804 in patients with advanced lung cancer. Conditions: Carcinoma, Non Small Cell Lung Intervention / Treatment: DRUG: PF-00299804 Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Masking: NONE

Inclusion Criteria: * Advanced NSCLC * Prior treatment with and failure of at least one regimen of chemotherapy and erlotinib or gefitinib * Prior treatment with no more than two chemotherapy regimens, including adjuvant treatment * Measurable disease Exclusion Criteria: * Chemotherapy, radiotherapy, biological or investigational agents within 4 weeks of baseline disease assessment * Patients who lack of tolerance of erlotinib therapy * Patients with known brain Metastases * Patients with demonstrated history of or presence of interstitial lung disease.

Study Objectives This is a prospective, multicenter phase II trial designed to determine efficacy and safety of Bortezomib plus Rituximab plus Bendamustine in patients with relapsed/refractory Waldenstrom's Macroglobulinemia. Conditions: Waldenstrom's Macroglobulinemia Intervention / Treatment: DRUG: Bortezomib-Rituximab-Bendamustine Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological proven diagnosis of Lymphoplasmacytic/cytoid lymphoma/Waldenstrom macroglobulinemia according to REAL/WHO Classification * Relapsed/refractory disease after receiving one line chemotherapy (rituximab). If patients received bortezomib or bendamustine and have obtained a partial response lasting at least two years. * Age >= 18 * Presence of at least one of the following criteria for the definition of active disease: Systemic symptoms or Hemoglobin less than 10 g/dL (due to lymphoma) or Platelets less than 100 x 109/L (due to lymphoma) or symptomatic splenomegaly or Bulky disease (>7 cm) or Hyperviscosity syndrome, peripheral neuropathy up to grade 1 (Waldenstrom's disease-related), hemolytic anemia, and immune complex vasculitis * Life expectancy >6 months * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * left ventricular ejection fraction (LVEF) ≥45% or FS ≥37% * Creatinine up to 1.5 x upper limit of normal * Conjugated bilirubin up to 2 x upper limit of normal * Alkaline phosphatase and transaminases up to 2 x upper limit of normal * Written informed content Exclusion Criteria: * Patients who received bortezomib or bendamustine first-line therapy, that or haven't obtained at least partial response nor partial response lasting at least two years. * Patients not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy * History of other malignancies within 3 years prior to study entry except for: adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage, localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent * Medical condition requiring long term use (>1 months) of systemic corticosteroids * Active bacterial, viral, or fungal infection requiring systemic therapy * Peripheral neuropathy of any grade ≥ 2 \[see Appendix Section A\] * Concurrent medical condition which might exclude administration of therapy * Cardiac insufficiency (NYHA grade III/IV) * Myocardial infarction within 6 months of entry on study * Severe chronic obstructive pulmonary disease with hypoxemia * Severe diabetes mellitus difficult to control with adequate insulin therapy * Hypertension that is difficult to control * Impaired renal function with creatinine clearance <30 ml/min * HIV positivity HBV positivity with the exception of patients HbsAg and HBV-DNA negative and Ab anti-HB core positive (these patients need to receive prophylaxis with Lamivudine) * HCV positivity with the exception of patients with HCV RNA negative * Participation at the same time in another study in with investigational drugs are used * Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins * Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent. * Women in pregnancy or breastfeeding

Study Objectives The purpose of this study is to evaluate whether treatment with a new drug called ZK-Epothilone (ZK-Epo) in patients with metastatic breast cancer helps to decrease or stop tumor growth. Conditions: Breast Neoplasm Intervention / Treatment: DRUG: Sagopilone (ZK 219477), DRUG: Sagopilone (ZK 219477) Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Metastatic breast cancer (meaning the cancer has spread beyond its original location) * At least one measurable lesion by CT or MRI * Progression of disease following previous therapy for breast cancer * Have received previous treatment with anthracyclines (e.g. doxorubicin\[Adriamycin or Doxil\] or epirubicin \[Ellence\]), taxanes (paclitaxel \[Taxol or Abraxane\] or docetaxel \[taxotere\]) for your breast cancer * Not be pregnant * Additional criteria to be determined at screening visit. Exclusion Criteria: * More than 3 previous chemotherapy regimens * More than one treatment with non cytotoxic agents for breast cancer therapy (e.g. herceptin \[trastuzumab\] or Avastin \[bevacizumab) * Prior treatment with epothilones (e.g. Ixabepilone) * Symptomatic brain metastases * Additional criteria to be determined at screening visit

Study Objectives The purpose of this study is to assess the effect of zoledronic acid on bone mineral density in prostatic cancer patients currently receiving androgen deprivation therapy. Conditions: Prostatic Neoplasms, Bone Density Intervention / Treatment: DRUG: Zolderonic acid (Zometa) Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Prostate cancer patients aged between 50-80 who is having or will have ADT. Baseline BMD in between -2 standard deviation (SD) and mean of that among young adults. Exclusion Criteria: * Patients with renal or liver problems, on calcium or other bisphosphonate therapy within six months before enrolling into the study. Patients who have: * Serum creatinine levels >212 µmol/L (2.4 mg/dL). * Creatinine clearance <50 ml/min. * WBC <4.0x109/L, Hgb <10 g/dL, platelets <140x109/L. Patients with known hypersensitivity to bisphosphonates. Patients with history of diseases with influence on bone metabolism, such as Page's disease of bone, primary hyperparathyroidism or osteoporosis.

Study Objectives A Phase I study to assess the safety and tolerability of AZD2281 in combination with Cisplatin in patients with advanced Solid Tumours. This is an open label-dose finding; to establish the maximum tolerated dose of AZD2281 combined with Cisplatin in patients with advanced solid tumours. Approximately 50 (max 60) patients from 2 countries will be enrolled Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: AZD2281, DRUG: Cisplatin Location: United States, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Life expectancy of at least 12 weeks * Histologically confirmed metastatic cancer, not amenable to surgery or radiation therapy with curative intent * Patients with measurable or non measurable disease according to RECIST Exclusion Criteria: * Less than 28 days from active therapy (ie any treatment used to treat the disease) or high dose radiotherapy * Brain Metastases or spinal cord compression unless irradiated at least 4 weeks before entry and stable without steroid treatment for >1 week * Persistent CTCAE Grade 2 or greater toxicities (excluding alopecia) caused by prior therapy

Study Objectives The purpose of this Phase 1b, multi-centre, dose escalation study is to find the maximum tolerated dose (MTD) of AZD1775 combined with olaparib in patients with refractory solid tumours Conditions: Refractory Solid Tumours, Relapsed Small Cell Lung Cancer (SCLC) Intervention / Treatment: DRUG: AZD1775, DRUG: Olaparib Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria for All Patients * Male and female patients ≥ 18 years of age. * Any prior palliative radiation therapy must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1. * Baseline laboratory values within 7 days of study drug(s) initiation: * ANC ≥ 1500/μL * Haemoglobin (Hgb) ≥10 g/dL without transfusion in the past 28 days * Platelets ≥ 100,000/μL * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN or ≤ 5 x ULN if known liver metastases. * Serum bilirubin within normal limits (WNL) or ≤1.5 x ULN in patients with liver metastases, or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well-documented Gilbert's Syndrome. * Serum creatinine ≤1.5 x ULN and creatinine clearance (CrCl) ≥ 51 mL/min * Female patients who are not of child-bearing potential, and fertile females of childbearing potential who agree to use two highly effective forms of contraception in combination from 2 weeks prior to study treatment and until 1 month after study treatment discontinuation, are not breastfeeding, and must have a negative serum or urine pregnancy test within 28 days of study treatment and confirmed prior to the start of study treatment on first day of dosing. * Male patients should be willing to abstain or use barrier contraception (i.e., condoms with a spermicide) for the duration of the study drug exposure and for 3 months after study treatment discontinuation. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential, unless the male patient is abstaining from sexual intercourse. * Predicted life expectancy ≥ 12 weeks. Inclusion Criteria Specific to Part A * Histologically confirmed refractory solid tumour for which there is no known or established treatment available with curative intent, after at least one course of systemic therapy for locally advanced or metastatic disease including chemotherapy, targeted therapy or hormonal therapy. * Measurable or non-measurable disease according to RECIST v1.1 Inclusion Criteria Specific to Part B * Relapsed small-cell lung cancer (SCLC) (defined as a histologically confirmed diagnosis of SCLC) with advanced disease (recurrent or metastatic). * Patients must have a confirmed response (either PR or CR) to first-line platinum therapy and then relapsed after completing that treatment. Patients who progressed whilst on platinum-containing treatment (platinum refractory) are not permitted to enter the study. Prior treatment with immunotherapy is permitted.. * Has agreed to the collection of archival tumour tissue or recent tumor biopsy sample, if taken for routine clinical purposes at baseline if archival tissue is not available for molecular biomarker analyses. * Measurable disease according to RECIST v1.1 criteria. Exclusion Criteria * Prior treatment with a PARP inhibitor. * Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to 1st dose of study treatment. * Use of anti-cancer treatment drug ≤ 21 days or 5 half-lives (whichever is shorter) prior to 1st dose of study treatment. For drugs for which 5 half-lives is ≤ 21 days, a minimum of 10 days between termination of the prior treatment and administration of study treatment is required. * Radiotherapy (except for palliative reasons) within ≤ 21 days prior to study treatment. * No other anti-cancer therapy (except for palliative local radiotherapy), biological therapy, or other novel agent is permitted while the patient is receiving study medication. Patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator. * Major surgical procedures ≤ 28 days of beginning study treatment, or minor surgical procedures ≤ 7 days. Patients must have recovered from any of the effects of any major surgery. No waiting period required following port-a-cath placement. * Persistent Grade >1 toxicity from prior cancer therapy (except alopecia or anorexia). * Patient has an inability to swallow oral medications. Note: Patients with percutaneous endoscopic gastrostomy (PEG) tube or receiving total parenteral nutrition (TPN) are not eligible. * Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage for at least 2 weeks after treatment. Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment. * Patient has had prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to the olaparib PK sub-study dosing and withheld throughout the study until 2 weeks after the last dose of study drug. * The use of sensitive substrates of CYP3A4, such as atorvastatin, simvastatin and lovastatin are prohibited in this study. Co-administration of aprepitant or fosaprepitant during this study is prohibited. * Caution should be exercised when inhibitors or substrates of P-glycoprotein (P-gp), substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with AZD1775. * Herbal preparations are not allowed throughout the study, including but not limited to: St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng. Patients should stop using these herbal medications 7 days prior to first dose of study treatment. * Any known hypersensitivity or contraindication to the components of the study drug AZD1775 or olaparib. * Patients with either previous or current myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML. * Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2. * Unstable angina pectoris * Congestive heart failure * Acute myocardial infarction * Conduction abnormality not controlled with pacemaker or medication * Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible) 16. AZD1775 should not be given to patients who have a history of Torsades des pointes (TdP) unless all risk factors that contributed to TdP have been corrected. 17. Mean resting corrected QTc interval using the Fridericia formula \[QTcF\]) ≥ 470 msec for female patients and ≥ 450 msec for male patients from 3 electrocardiograms (ECGs) performed 2-5 minutes apart at study entry or congenital long QT syndrome. . 18. Pregnant or breastfeeding. 19. Serious known active infection at the time of enrolment, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment. 20. Presence of other known active invasive cancers. 21. Psychological, familial, sociological, or geographical conditions that do not permit compliance with protocol. 22. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (< 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. 23. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). 24. Previous allogeneic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection will exclude patients from the pharmacogenetic portion of the study. If a patient declines to participate in the optional exploratory pharmacogenetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.

Study Objectives A Randomized, Double-Blind, Vehicle-Controlled, Multicenter Study to Assess the Efficacy and Safety of Methyl aminolevulinate hydrochloride (MAL) 16.8% cream (CD06809-41) versus vehicle cream in the treatment of thin and moderately thick, non-hyperkeratotic, non-pigmented actinic keratosis of the face and scalp when using daylight photodynamic therapy (DL-PDT). Conditions: Actinic Keratoses Intervention / Treatment: DRUG: MAL 16.8% cream, DRUG: MAL Vehicle Cream Location: United States, Puerto Rico Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Participants aged ≥ 18 years at the Screening visit. * Participants had at least 4, but no more than 12, clinically-confirmed thin or moderately thick, non-hyperkeratotic, non-pigmented AKs located on the face (e.g., forehead, cheek, chin), and balding scalp. * Female Participants of non-childbearing potential. * Participants fully understood and signed an ICF before any investigational procedure(s) are performed. Exclusion Criteria: * Participants with pigmented AK in the treatment areas. * Female participants who were pregnant, nursing, or planning a pregnancy during the study. * Participants with a clinical diagnosis of a skin disease other than AK. * Immunocompromised participants. * Participants with any condition that may be associated with a risk of poor protocol compliance.

Study Objectives This open-label, multicenter,dose-escalating phase I study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of MIL62 in Chinese patients with relapsed/refractory CD20-positive B-cell non-Hodgkin lymphoma(NHL) for whom no treatment of higher priority was available. Conditions: CD20-positive B Cell Non-Hodgkin Lymphoma Intervention / Treatment: DRUG: Recombinant Humanized Monoclonal Antibody MIL62 Injection Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult patients, >=18 years of age; * Diagnosis of Refractory/relapsed CD20+ B-cell lymphoma or B-CLL * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy >6 months * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 2 months after discontinuation of all study treatments * Able and willing to provide written informed consent and to comply with the study protocol Exclusion Criteria: * Prior use of any investigational antibody therapy within 3 months of study start * Prior use of any anti-cancer vaccine * Prior administration of radioimmunotherapy 3 months prior to study entry * Central nervous system lymphoma * History of other malignancy * Evidence of significant, uncontrolled concomitant disease * Abnormal laboratory values * Patients with progressive multifocalleukoencephalopathy (PML) * Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C(including HBsAg,HBcAb positive with abnormal HBV DAN or HCV RNA ) * Known severe allergic reaction or/and infusion reaction to monoclonal antibody.

Study Objectives This study intends to evaluate the feasibility and treatment efficacy of adding an antibody blocking the epidermal growth factor (EGF) pathway to a neoadjuvant approach with proven efficacy developed at New York University. Conditions: Gastric Cancer, Stomach Cancer Intervention / Treatment: DRUG: Cetuximab, DRUG: Irinotecan, DRUG: Cisplatin, PROCEDURE: Surgery, DRUG: 5-FU, RADIATION: Radiation 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 signed an approved informed consent. * must have histologically documented untreated gastric/GEJ carcinoma (clinical stage T3 N0 or T4, or any T with N1-N3 M0) * Patients with tumor tissue available for assessment of EGF receptor status by immuno-histochemistry (IHC). * Patients with Performance Status 0-2. * Patients, 18 years and older, must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. * Bone marrow function: absolute neutrophil count (ANC) at least 1,500/ul; platelets at least 100,000/ul. * Renal function: creatinine not greater than 1.5 x institutional upper limit of normal (ULN). * The PT and PTT should be within the range of normal values * Hepatic function: bilirubin not greater than 1.5 x ULN; aspartate aminotransferase (AST) not greater than 2.5 x ULN. Exclusion Criteria: * Acute hepatitis or known HIV. * Active or uncontrolled infection. * Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, and congestive heart failure. * Prior therapy that affects or targets the EGF pathway. * Prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA). * Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).

Study Objectives This is an open label, single arm trial of PTG-300 in subjects with PV who are newly diagnosed or for whom current therapy is not sufficient to control their hematocrit and have hematocrit \>48% prior to dosing. The PTG-300 dose and schedule may be adjusted every 2 to 4 weeks to maintain hematocrit \<45% with a target of \<43%. Subjects may receive PTG-300 treatment for up to 52 weeks. Conditions: Polycythemia Vera Intervention / Treatment: DRUG: PTG-300 Location: Korea, Republic of, Malaysia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Known diagnosis of polycythemia vera. * Hematocrit >48% before dosing. * Evidence of hematocrit >48% three or more times in the 28 weeks before dosing or five or more times in 52 weeks before dosing (except for newly diagnosed patients). * Clinically reasonable alternative causes for erythrocytosis have been evaluated and excluded. * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. Exclusion Criteria: * Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 3 months of Screening. * Active or chronic bleeding within 4 weeks of Screening. * Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). * Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 3 months of dosing; any infection requiring systemic antimicrobial therapy within 4 weeks of dosing. Prophylactic antibiotics are allowed. * Any serious or unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject from properly providing informed consent or any condition which would jeopardize compliance with the study. * Known primary or secondary immunodeficiency. * Known positive for active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection. * Any surgical procedure requiring general anesthesia within 1 month prior to Screening or planned elective surgery during the study. * History of invasive malignancies within the last 2 years, except non-melanoma skin cancer and localized curatively treated prostate cancer or cervical cancer. * Current or recent history of alcohol dependence or illicit drug use within 1 year prior to Screening.

Study Objectives Cooking for Health Optimization with Patients (CHOP) is the first known multi-site prospective cohort study with a nested Bayesian adaptive randomized trial in the preventive cardiology field of culinary medicine. It is also the first known longitudinal study to assess the impact of hands-on cooking and nutrition education on patient outcomes, with those classes taught by medical students and other future and current medical professionals who have first been trained in those classes on how to integrate diet and lifestyle counseling of patients with their respective scopes of clinical practice. CHOP is the primary research study of the world's first known medical school based teaching kitchen, The Goldring Center for Culinary Medicine at Tulane University School of Medicine. Medical trainees and professionals are followed in this study long-term to understand how the classes impact their competencies in patient counseling, attitudes about the counseling, and their own diets. Patients who consent to being randomized to these classes compared to standard of care are studied within the nested Bayesian adaptive randomized trial to understand how the classes impact their health outcomes, clinical and food costs, and the costs of health systems caring for these patient populations. CHOP is designed as a pragmatic population health trial to hopefully improve healthcare effectiveness, equity, and cost by establishing an evidence-based, scalable, sustainable model of healthcare intervention targeting the social determinants of health, while complementing the pharmacological and/or surgical management of patients. Conditions: Cardiovascular Diseases, Cardiovascular Risk Factor, Nutrition Disorders, Diabetes, Hypertension, Cancer, Depression, Obesity, Physical Activity Intervention / Treatment: BEHAVIORAL: Treatment 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: * 7 to 115 years of age (patients), and currently a medical trainee or professional (including for physicians, nurses, physician assistants, and dieticians) Exclusion Criteria: * Inability to complete at least 2 intervention classes

Study Objectives Trastuzumab is approved for the treatment of HER2-positive breast cancer and gastric cancer. The recent study showed that HER2 overexpression or amplification is noted about 5-15% of total biliary tract cancer patients. The aim of this study is to evaluate the efficacy and safety of trastuzumab in the combination of current standard gemcitabine plus cisplatin. Conditions: Cholangiocarcinoma, Biliary Tract Cancer, HER-2 Protein Overexpression, HER-2 Gene Amplification Intervention / Treatment: DRUG: Trastuzumab Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * The subject with disease that is not amendable to a curative treatment approach or locally advanced or metastatic or unresectable CCC with histological diagnosis * At least one measurable(per RECIST 1.1) lesion * Primary or metastatic tumor with HER2 positive defined on IHC2+, FISH+ or IHC3+ * ECOG Performance status 0 or 1 * At least 3 months for life expectancy Common inclusion criteria * Men or women over 19 years at time of signing ICF * Signed Informed Consent Form Exclusion Criteria: * Received prior chemotherapy for advanced/metastatic disease (the adjuvant/neoadjuvant chemotherapy completed at least 6 months before enrolled will be accepted) * Not recovery from toxicities related to any prior treatments excluding alopecia (eg, neurological toxicity to ≥ Grade 2) * History of malignancy other than CCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as carcinoma in situ or thyroid papillary carcinoma Hematology, chemistry or organ function * ANC < 1.5 × 109/L, or Platelet < 100 × 109/L * Total bilirubin > 1.5 × ULN; or AST/ ALT > 2.5 × ULN (or if the tumor has expanded into the liver, > 5 × ULN); or, alkaline phosphatase > 2.5 × ULN (or > 5 × if the tumor has expanded into the liver, or > 10 × ULN if the tumor has expanded into the brain without liver,); or albumin < 2.5 g/dL * Creatinine clearance < 60 mL/min(calculated using the Cockcroft-Gault formula) Other exclusion criteria related to IP * History of proved congestive heart failure; angina with medication; evidence of transmural myocardial infarction on ECG; uncontrolled hypertension(systolic> 180 mmHg or diastolic> 100 mmHg); clinically significant heart valve disease; uncontrolled arrhythmia * LVEF < 50% (calculated by cardiac sonography or MUGA) * Subject with rest dyspnea due to metastatic tumor or other disease or who needs oxygen therapy * Chronic or high-dose corticosteroid treatment * Clinically significant Hearing impairment Common exclusion criteria * History or evidence of CNS metastases * Interstitial pneumonia or pulmonary fibrosis with symptom and exact lesion on chest X-ray * Hearing loss * Uncontrolled significant systemic disease (eg, infection or uncontrolled DM) * Pregnant or lactating females * Sexually active fertile subjects without contraception * Treatment with other investigational therapy within 4 weeks prior to initiation of study treatment * Radiotherapy within 4 weeks prior to initiation of study treatment (the rest at least 2 weeks after palliative radiotherapy for bone metastasis and recovery from the effects of radiation will be accepted.) * Major surgery within 4 weeks prior to initiation of study treatment * History of HIV and active HBV or HCV * Previously identified allergy or hypersensitivity to components of the study treatment formulations

Study Objectives Taking into account the excellent prognosis of patients with HPV-positive oropharyngeal cancer with \< 10 pack-year smoking, the investigators hypothesize that reducing the intensity of therapy for these patients will reduce treatment sequelae, notably long-term dysphagia, without affecting their cure rates. The main Aim is to assess whether reducing treatment intensity, by replacing concurrent chemotherapy with cetuximab, will indeed achieve improved long-term toxicity. The primary objectives include the following: to confirm that reducing treatment intensity in patients with HPV-related oropharyngeal cancer and \< 10 pack-year smoking history by replacing concurrent chemotherapy with concurrent cetuximab, does not significantly increase the proportion of patients whose tumors recur, compared to our previous experience in similar patients receiving chemo-RT and to compare the toxicity in patients receiving cetuximab-RT to similar patients treated with 7 weeks of chemotherapy concurrent with RT ("standard therapy") in UMCC 2-21. Conditions: Squamous Cell Carcinoma of the Oropharynx, HPV Intervention / Treatment: DRUG: Cetuximab, RADIATION: Radiotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have pathologically-confirmed, previously untreated,stage III-IV(excluding N3 or T4) squamous cell carcinoma of the oropharynx, without evidence of distant metastasis * Pretreatment tumor biopsy with sufficient tumor for HPV or p16 analysis is required. The tumor must be HPV(+) or p16(+) Smoking history <10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing tobacco, and/or marijuana). One cannabis joint is equivalent to 5 cigarettes. (Aldington etal, Thorax 2007; 62:1058-1063). Smoking status definitions (National Health Interview Survey and Behavioral Risk Factor Surveillance System (Nelson DE etal al, Am J Pub Health 2003;93:1335): * Smokers: smoking now every day or some days in past month * Quitters: at least 100 cigarettes/lifetime and not smoking in the past 1-12 months * Former smoker: at least 100 cigarettes/lifetime and not smoking >12 months * Never smokers: <100 cigarettes (or equivalent)/lifetime * KPS > 80 (see Appendix A) * Patients must undergo pre-treatment endoscopic tumor staging and PET-CT scanning * Laboratory criteria: * WBC > 3500/ul * granulocyte > 1500/ul * Platelet count > 100,000/ul * Total Bilirubin < 1.5 X ULN * AST and ALT < 2.5 X ULN * Creatinine clearance >30 cc/min * Patients must sign study specific informed consent * Patients must have, in the opinion of a treating physician, tumor that is accessible to biopsy in the clinic. Exclusion Criteria: * Prior head and neck malignancy or history of other prior non-head and neck malignancy (excluding skin cancer and early stage treated prostate cancer) within the past 3 years * Prior head and neck radiation or chemotherapy * Any medical or psychiatric illness, which in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment or limit compliance with study requirements * Patients residing in prison * Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule)

Study Objectives The purpose of this study is to determine whether pralatrexate, given with vitamin B12 and folic acid, is effective in the treatment of relapsed or refractory B-cell Non-Hodgkin's lymphoma (NHL). The study will also investigate the safety of pralatrexate with vitamin B12 and folic acid in this participant population. Additionally, this study includes the collection of blood samples to investigate the pharmacokinetics (PK) of pralatrexate in this participant population (PK is the activity of a drug in the body over a period of time, including how the drug is absorbed, distributed in the body, localized in the tissues, and excreted from the body). Conditions: Lymphoma, B-Cell Intervention / Treatment: DRUG: Pralatrexate, DIETARY_SUPPLEMENT: Vitamin B12, DIETARY_SUPPLEMENT: Folic 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: * Histologically/cytologically confirmed, measurable (lesion or node =2 cm by CT \[at least 1 cm if by spiral CT\]) B-cell Non-Hodgkin's Lymphoma, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification * Progressive or persistent disease after ≥ 1 prior treatment(s) * Recovered from toxic effects of prior treatment * At least 4 weeks since most recent cytotoxic therapy * Easter Cooperative Oncology Group (ECOG) performance status ≤ 2 * Adequate blood, liver, and kidney functions as defined by laboratory levels * 1.0 mg/day orally of folic acid for at least 7 days prior \& 1 mg intramuscular of vitamin B12 within 10 weeks of the planned start of pralatrexate * Females of childbearing potential must agree to use medically acceptable birth control from start of pralatrexate until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment * Males who are not surgically sterile must agree to use medically acceptable birth control from start of pralatrexate until at least 90 days after the last administration of pralatrexate * Available for repeat dosing and follow-up * Able to give written informed consent Exclusion Criteria: * Relapsed participants with diffuse large B-cell lymphoma (DLBCL) who are candidates for high-dose therapy and autologous stem cell transplantation (SCT) and for whom high-dose therapy and autologous SCT is a standard curative option * Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancies other than those exceptions listed above, the participant must be disease-free for ≥ 5 years. Participants with other prior malignancies < 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease * Congestive heart failure Class III/IV according to the New York Heart Association Functional Classification * Uncontrolled hypertension * Known human immunodeficiency virus (HIV)-positive diagnosis * Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Participants who received prophylactic CNS treatment are eligible. * Participants who have undergone an allogeneic SCT * Participants who have relapsed < 100 days from the time of an autologous SCT * Participants with disease refractory to peripheral blood SCT or who have relapsed < 100 days from the time of transplant * Active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the participant to receive protocol treatment. * Major surgery within 14 days of enrollment * Receipt of any conventional chemotherapy or radiation therapy (encompassing a substantial \[> 10%\] amount of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study * Receipt of systemic corticosteroids within 1 week of study treatment, unless participant has been taking a continuous dose of no more than 10 mg/day of prednisone or its equivalent for at least 1 month * Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study * Previous exposure to pralatrexate * Females who are pregnant or breastfeeding

Study Objectives The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD4877 based on the side effects experiences by patients that receive AZD4877 on a weekly basis Conditions: Neoplasms Intervention / Treatment: DRUG: AZD4877 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: * Advanced solid tumors for which standard treatment doesn't exist or is no longer effective. * Relatively good overall health other than your cancer. Exclusion Criteria: * Poor bone marrow function (not producing enough blood cells). * Serious heart conditions. * Poor liver or kidney function.

Study Objectives This is a two-part study that will determine, if: 1) the combination of ridaforolimus and dalotuzumab will improve progression-free survival compared to exemestane; and 2) the combination of ridaforolimus and dalotuzumab will improve progression-free survival compared to both ridaforolimus and dalotuzumab as single agents, in participants with breast cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: ridaforolimus + dalotuzumab, DRUG: exemestane, DRUG: ridaforolimus, DRUG: dalotuzumab Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria The prospective participant must meet, at least, all of the criteria below to be eligible for study participation. The participant: * Has a confirmed diagnosis of breast cancer that is metastatic or locally advanced and is estrogen receptor positive and human epidermal growth factor receptor 2 (HER-2) negative ; * Is post-menopausal; * Is at least 18 years of age; * Has a life expectancy of at least 3 months; * Has had a recurrence or progression of cancer after prior treatment and patient has received at least one line of endocrine therapy for metastatic disease, OR the patient's cancer has recurred within 6 months after the last dose of anastrozole or letrozole; * Has an available archival tumor specimen; * Has voluntarily agreed to participate by signing informed consent. Exclusion Criteria If the prospective participant meets any of the criteria below (among others determined by the study staff) they will NOT be eligible for study participation. The participant: * Is receiving any other systemic tumor therapy; * Has previously received rapamycin or rapamycin analogs; * Has received prior treatment with insulin-like growth factor 1 receptor (IGF-1R) inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, or other experimental agents that target the PI3K, protein kinase B (AKT), or mammalian target of rapamycin (mTOR) pathways; * Has known allergy to macrolide antibiotics; * Has an active infection that requires antibiotics; * Has significant or uncontrolled cardiovascular disease; * Has poorly controlled Type 1 or 2 diabetes mellitus; * Is known to be human immunodeficiency virus (HIV) positive; * Has a known history of active Hepatitis B or C.

Study Objectives The goal of this clinical research study is to learn about the safety of LY2510924 in combination with cytarabine and idarubicin in patients with relapsed or refractory AML. We will also study if LY2510924 in combination with cytarabine and idarubicin can help to control relapsed or refractory AML. LY2510924 is designed to help cancer cells move from the bone marrow into the bloodstream, where they are exposed to chemotherapy (in this case, cytarabine and idarubicin). This is an investigational study. LY2510924 is not FDA approved or commercially available. Its use in this study is investigational. Cytarabine and idarubicin are approved to treat certain types of leukemia. Their use in this study in combination with LY2510924 is investigational. Up to 36 patients will take part in this study. All will be enrolled at MD Anderson. Conditions: Leukemia Intervention / Treatment: DRUG: LY2510924, DRUG: Idarubicin, DRUG: Cytarabine 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: * All patients with histologically or cytologically confirmed relapsed or refractory AML \[except acute promyelocytic leukemia\]; relapsed disease or refractory (refractory to a non-high-dose cytarabine-containing regimen only); receiving 1st, 2nd or 3rd salvage; any cytogenetic or molecular abnormality. Patients with secondary AML (after prior myelodysplasia or therapy for other cancers) will be included. * Patients with prior autologous and allogeneic hematopoietic stem cell transplantation are eligible if patients are off immunosuppression for greater than 14 days and have no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD. * Clinical laboratory values should be as follows: (a) White blood count < 30,000/µL; (b) Absolute Blasts in peripheral blood < 20,000 (treatment with Hydroxyurea is permitted up to 24 hrs prior to LY251092 administration to achieve blast counts < 20,000 prior to enrollment). * Patients must be 18-70 years old. * Patients must have a performance status of 0-2 (Zubrod scale). * Patients must have adequate renal function (serum creatinine less than or equal to 1.3 mg/dL). If creatinine is > 1 mg/dL the creatinine clearance should be > 40 mL/min as calculated using the Cockcroft-Gault formula. * Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 X the upper limit of normal \[ULN\] for the reference lab unless due to leukemia or congenital hemolytic disorder or bilirubin excretion disorder). Patients with hepatic dysfunction (SGOT/SGPT up to less than or equal to 5 X ULN) due to organ infiltration by disease may be eligible after discussion with the Principal Investigator and appropriate dose adjustments will be considered. * Patients must have normal cardiac ejection fraction (left ventricular ejection fraction \[LVEF\] greater than or equal to 50%). * Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study, in keeping with the policies of the hospital. * Negative urine or blood pregnancy test for women of childbearing potential. * Female patients must not be pregnant or lactating. Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception. Exclusion Criteria: * Patients with untreated or uncontrolled life-threatening infection. * Patients who have received chemotherapy and/or radiation therapy within 2 weeks unless there is evidence of rapidly progressive disease. In the event that subjects have received chemotherapy < 2 weeks from the date of enrollment, they may be included provided they have recovered from the associated non-hematological toxicities to less than or equal to grade 1. Hydroxyurea is allowed up to 24 hours prior to starting therapy in the setting of rapidly proliferating disease. * Patients who have received an investigational anti-cancer drug within two weeks (or five half-lives, whichever is shorter) of LY251092 administration. * History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date. * History of another malignancy. Exception: Patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible. * Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent or cooperate and participate in the study or with the interpretation of the results. * Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression (patients with controlled central nervous system (CNS) disease, i.e. asymptomatic and currently receiving concurrent intrathecal chemotherapy, are eligible upon discussion with the Principal InvestigatorI). * Known active Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection (patients with chronic or cleared HBV and HCV infection, are eligible).

Study Objectives This randomized double-blind, placebo-controlled phase 2 trial is evaluating superiority of Letrozole-palbociclib combination versus letrozole-placebo combination in ER positive endometrioid adenocarcinoma of endometrium Conditions: Endometrial Cancer Intervention / Treatment: DRUG: Palbociclib/placebo, DRUG: Letrozole Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histological confirmed endometrial cancer of endometrioid type. Mixed tumor histology is allowed if the non-endometrioid component is less than 5%. Tumor must be estrogen receptor positive. * Patients may have received adjuvant chemotherapy for stage 1 or 2. * Patients may have received any lines of chemotherapy for primary advanced (stage 3-4) or relapsed disease. * Patients may have received external beam radiotherapy, brachytherapy, and surgery. * Patient may have received maximum one line of endocrine therapy containing MPA/Megace only. * Patients must have measureable disease or evaluable disease on CT scan according to RECIST 1.1 outside irradiated field. * Patients must give informed consent * Patients must have a WHO performance status of 0-1 * Patients must have an adequate bone-marrow, renal and hepatic function * Life expectancy of at least 12 weeks * Patients must be fit to receive combination therapy * Patient's age >18 years * Patient is post-menopausal. Patients under the age of 55 with intact ovaries shall undergo hormonal verification. * Patients with preserved reproductive capacity must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment Exclusion Criteria: * Non-endometrioid adenocarcinomas, sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers. * Previous anti-cancer endocrine therapy other than MPA/Megace. This means that eg. tamoxifen is not allowed prior to study entry. * Concurrent cancer therapy * Previous treatment with Palbociclib or other CDK inhibitors. * Concurrent treatment with an investigational anticancer agent or participation in another anticancer clinical trial within 21 days before entering into study. * Treatment within 21 days prior to randomization with any investigational drug, radiotherapy, * Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period. * Previous malignant disease, except patients with other malignant disease, for which the patient has been disease-free for at least three years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin. * Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed. * Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study. * Known uncontrolled hypersensitivity to the investigational drugs. * History of major thromboembolic event defined as: * History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months. * History of clinically significant hemorrhage in the past 3 months. * Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization). * Significant cardiovascular diseases, including uncontrolled hypertension, uncontrolled clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > NYHA III, severe peripheral vascular disease, clinically significant pericardial effusion. * Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards. * Active or chronic hepatitis C and/or B infection * Persistence of clinically relevant grade 3-4 therapy related toxicity from previous chemo and/or radiotherapy * Known hypersensitivity to the trial drugs, or to their excipients. * Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug * Unable or unwilling to swallow tablets/capsules

Study Objectives The purpose of this study is to determine the safest and maximum tolerated dosing regimens for intraperitoneal oxaliplatin with intravenous docetaxel and intravenous oxaliplatin with intraperitoneal docetaxel for recurrent ovarian, primary peritoneal, or fallopian tube cancer. Conditions: Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer Intervention / Treatment: DRUG: intravenous docetaxel with intraperitoneal oxaliplatin, DRUG: intravenous oxaliplatin with intraperitoneal docetaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Recurrent histologically confirmed platinum-sensitive or platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer * Subjects may not have had > 3 prior regimens and must not have had a platinum or taxane agent within the past 6 months. Last chemotherapy must have been > 4 weeks prior to enrollment. Subjects may not have had prior whole abdomen or pelvic radiation. Patients may not have had > 6 cycles of an alkylating agent or > 450 mg/m2 of doxorubicin. * ECOG Performance Score of ≤2 (Appendix A) * Adequate bone marrow as evidenced by: * Absolute neutrophil count > or equal to 1,500/uL * Hemoglobin > or equal to 8 g/dl * Platelet count > or equal to 100,000/uL * Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL * Adequate hepatic function as evidenced by: * Serum total bilirubin < 1.5 mg/dL * Alk Phos, AST/ALT must be < 3x ULN or <5x ULN if hepatic mets. * AST/ALT < 3X the ULN for the reference lab * Patients must be recovered from both the acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy * Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial. * Patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method) Exclusion Criteria: * Patients with an active infection or with a fever > 101.30 F within 3 days of the first scheduled day of protocol treatment * Patients with active extra-abdominal metastases * Patients with active CNS metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for 3 weeks are eligible for the trial * History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin or cervical intra-epithelial neoplasia * Patients with known hypersensitivity to any of the components of docetaxel or oxaliplatin * Patients who received pelvic or abdominal radiotherapy * Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication) * Peripheral neuropathy ≤ Grade 2 * Patients who are pregnant or lactating * Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results. * History of allogeneic transplant * Known HIV or Hepatitis B or C (active, previously treated or both)

Study Objectives This study is a multicenter phase II trial which primary objective is to assess the anti-lymphoma activity of atezolizumab associated with a BCL-2 inhibitor (GDC-199, venetoclax) and an anti-CD20 monoclonal antibody (obinutuzumab) in three separate cohorts: * relapsed/refractory follicular lymphoma (FL) patients * relapsed/refractory aggressive (DLBCL) lymphoma patients * relapsed/refractory other indolent (iNHL) lymphoma patients (MZL and MALT) Conditions: Follicular Lymphoma, Diffuse Large B Cell Lymphoma, Marginal Zone Lymphoma, Mucosa Associated Lymphoid Tissue Intervention / Treatment: DRUG: Atezolizumab, DRUG: Obinutuzumab, DRUG: Venetoclax Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically documented CD20-positive follicular lymphoma (WHO grade 1, 2, or 3a) patients for cohort 1 * Patients with either histologically documented CD20-positive Diffuse large-cell lymphoma (including transformations of low-grade lymphoma into DLBCL) or follicular lymphoma CD20+ grade 3b, or primary cutaneous DLBCL leg type, or primary mediastinal (thymic) large B-cell lymphoma, or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, or unclassifiable B-cell lymphoma with features intermediate between DLBCL and Hodgkin (WHO classification) for cohort 2 * Patients with relapsed/refractory indolent lymphoma (marginal zone (MZL) or measurable mucosa-associated lymphoid tissue (MALT) lymphoma) for cohort 3 * Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option * Aged 18 years or more with no upper age limit * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 * Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan, or Positron Emission Tomography (PET) scan without IV contrast at diagnosis with at least one hypermetabolic lesion * Signed written informed consent * Life expectancy ≥ 3 months * Females of childbearing potential (FCBP) must agree to use one reliable form of contraception or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 18 months after discontinuation of all study treatments * Male patients and their partner (FCBP) must agree to use two reliable forms of contraception (condom for males and hormonal method for partners) during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 18 months after discontinuation of all study treatments * Patient covered by any social security system Exclusion Criteria: * Lymphocytic lymphoma (LL), waldenström macroglobulinemia, unmeasurable MALT lymphoma, Mantle Cell Lymphoma (MCL) and Follicular lymphoma for cohort 3 * Known CD20 negative status at last biopsy done (Biopsy at relapse/progression is mandatory) * Central nervous system or meningeal involvement by lymphoma * Prior history of Progressive Multifocal Leukoencephalopathy (PML) * Documented infection with HIV * Active Hepatitis B (HB) (positive Hepatitis B surface antigen (Ag-HBs) OR positive serology to hepatitis B (positive Ag-HBs or Hepatitis B core antibody (anti-HBc) or Polymerisation Chain Reaction (PCR) for viral DNA of HBV) Active Hepatitis C (HC) infection (patients with positive HCV serology (anti-HCV) are eligible only if PCR is negative from known HCV RNA) * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) before inclusion, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to first administration of study drug * Active immune-related disease criteria * Left Ventricular Ejection Fraction (LVEF) < 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan * Any serious active disease or co-morbid medical condition (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including uncontrolled obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision) * Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis * Any of the following laboratory abnormalities: * Hemoglobin < 9 g/dL * Absolute neutrophil count (ANC) < 1,000 cells/mm3 (1.0 G/L) unless due to lymphoma * Platelet count < 75,000/mm3 (75 x 109/L) unless due to lymphoma * Serum glutamic-oxaloacetic transaminase (SGOT) / Aspartate Transaminase (AST) or Serum Glutamic-Pyruvate Transferase (SGPT) / Alanine Transaminase (ALT) 3.0 x upper limit of normal (ULN) unless disease involvement * Serum total bilirubin > 2.0 mg/dL (34 μmol/L), except if disease related or in case of Gilbert syndrome * Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL /min * International normalized ratio (INR) ≤ 1.5 x ULN for patients not receiving therapeutic anticoagulation * Partial thromboplastin time (PTT) or activated PTT (aPTT) > 1.5 x ULN * Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 3 years. Exceptions will be allowed for patients with non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or any surgically removed stage 0 (in situ) carcinoma * Any serious medical condition, laboratory abnormality (other than mentioned above), or psychiatric illness that would prevent the subject from signing the informed consent form * Contraindication to any drug contained in the study treatment regimen * Previous treatment with obinutuzumab, atezolizumab or venetoclax * Use of any standard or experimental anti-cancer drug therapy within 28 days prior to first administration of study drug * Use of warfarin prior to first administration of study drug and throughout all treatment period (because of potential drug-drug interactions that may potentially increase the exposure of warfarin) * Patients taking corticosteroids within 4 weeks prior to first administration of study drug, unless administered at a cumulated dose equivalent to ≤ 3.5mg/kg (within these 4 weeks). * Use of the following agents prior to first administration of study drug: Strong and moderate CYP3A inhibitors (including grapefruit juice); Strong and moderate CYP3A inducers * Pregnant or lactating females * Person deprived of his/her liberty by a judicial or administrative decision * Adult person under legal protection * Person hospitalized without consent * Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness

Study Objectives DKN-01 is a humanized monoclonal antibody (Mab) with neutralizing activity against Dkk-1 and is being developed as an anti-neoplastic agent. This study is designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of DKN-01 in combination with gemcitabine and cisplatin in patients with carcinoma primary to the intra- or exta-hepatic biliary system or gallbladder. Conditions: Carcinoma of Intrahepatic and Extra-hepatic Biliary System, Carcinoma of Gallbladder, Bile Duct Cancer, Cholangiocarcinoma Intervention / Treatment: DRUG: DKN-01, DRUG: gemcitabine, DRUG: cisplatin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient has carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder. * Patient must have sufficient tumor tissue available for submission. * For patients who have received prior cryotherapy, radiofrequency ablation, radioembolization, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, at least 28 days must have elapsed since that therapy, and lesions that have not been treated with local therapy must be present and measurable. * Patients may have received prior adjuvant chemotherapy with gemcitabine with or without cisplatin, as long as 6 months have elapsed since last treatment. * Patients must have one or more tumors measurable on radiographic imaging as defined by RECIST. * ECOG PS of 0 or 1. Patients with an ECOG PS of 2 may be entered upon review and approval of the medical monitor. * Estimated life expectancy of at least 3 months. * Disease-free of active second/secondary or prior malignancies for ≥ 2 years with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast. * Adequate hematological, renal, hepatic and coagulation laboratory test results. * Women of child bearing potential and men must agree to use adequate contraception during the study and for 6 months after their last dose of study drug. * Available for the duration of the study and are willing to follow study-specific procedures. * Provide written informed consent Exclusion Criteria: * New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia. * Have Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome. * Active, uncontrolled bacterial, viral, or fungal infections. * Known to be human immunodeficiency virus (HIV) positive or has untreated, active hepatitis B. * History of major organ transplant. * History of an autologous/allogenic bone marrow transplant. * Serious nonmalignant disease. * Pregnant or nursing. * History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant. * Symptomatic central nervous system (CNS) malignancy or metastasis. * Clinically significant peripheral neuropathy * Known osteoblastic bony metastasis. * Treatment with surgery or chemotherapy within 21 days prior to study entry or radiation within 14 days of study entry. * Previously treated with an anti-Dkk-1 therapy. * Other exclusions apply

Study Objectives This study aims to investigate if the proportion of neuroendocrine tumor (NET) patients with normal vitamin values can be increased, with vitamin suppletion and a personalized diet, Effects of the intervention will be evaluated by quantitative analysis of blood and urine and questionnaires. The measurements, will be performed at baseline (t=0), after 4 weeks (t=4) and after 18 weeks at end of study (t=18). Furthermore at t=18 a semi-qualitative interview will be performed. Conditions: Neuroendocrine Tumor Intervention / Treatment: DIETARY_SUPPLEMENT: Vitamin supplement;, OTHER: Diet advice Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult patients aged ≥ 18 years * NET-patients with serotonin producing or non-serotonin producing tumors, with gastro-intestinal, pancreatic, bronchopulmonary or unknown primary tumor site and with metastasized or irresectable disease * Ability to comprehend Dutch (both reading and writing). * Written informed consent provided. * Use of somatostatin analogue for > 6 months. Exclusion Criteria: * Estimated life expectancy less than 6 months. * Patients who have a history of another primary malignancy, except for radical and adequately treated malignancies from which the patient has been disease free for ≥ 1 year. * Major abdominal surgery during study period. * Patients already participated in the DIVIT-pilot study * Known hypersensitivity of (components of) somatostatin analogue

Study Objectives This is an open-label, multi-centre, randomised Phase III study, looking at a series of 480 patients up to the age of 65 with newly diagnosed multiple myeloma (MM) not previously treated. They will receive VAD or Velcade®/dexamethasone combination as induction treatment plus/minus (±) dexamethasone/cyclophosphamide/etoposide/cisplatin (DCEP) followed by autograft as first-line therapy, as the investigators try to compare the complete remission (CR) rate (with negative or positive immunofixation) at the end of their induction treatment. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Velcade Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Recently diagnosed MM according to the criteria of the South West Oncology Group (SWOG) * Not previously treated, apart from local radiotherapy, in the case of a threatening or incapacitating lesion, and/or a 4-day block of dexamethasone (40 mg/mL) in an emergency * Stage II or III disease according to the Durie and Salmon classification or Stage I disease with symptomatic bone lesion * < 65 years of age * Ability to give signed informed consent * Secretion of a measurable monoclonal spike (> 10 g/l in the serum or 0.2 g/24h in the urine) * Negative pregnancy test at inclusion (if necessary) * Absence of active infection. In the case of infection, appropriate antibiotic therapy must be administered and patients must have been apyretic for 48 hours before the start of treatment with VAD or Velcade®/dexamethasone Exclusion Criteria: * ECOG performance status > 2 * History of cancer (other than basal cell carcinoma or carcinoma of the cervix in situ) * Life expectancy < 2 months * Confirmed amyloidosis * Positive HIV serology * Serious psychiatric item in the history * Renal failure requiring dialysis * Uncontrolled diabetes, contra-indicating the use of corticosteroids * Peripheral neuropathy National Cancer Institute (NCI) grade > 2 (Annex 5) * Clinical signs of heart failure or coronary heart disease * Bilirubin > 3 x normal * Transaminases or gamma-glutamyl transpeptidase (GT) > 4 x normal * Platelets < 50 x 10\^9/l during the 15 days prior to inclusion * Neutrophils < 0.75 x 10\^9/l during the 15 days prior to inclusion * Use of an investigational medicinal product during the 30 days prior to inclusion * Known hypersensitivity to bortezomib, boron or mannitol

Study Objectives The purpose of this study is to test what effects (good and bad) a new cancer vaccine will have on participants and their cancer, when administered before and after their autologous hematopoietic cell transplant (HCT). The name of the vaccine is called Dendritic Cell Survivin Vaccine (DC:AdmS). The vaccine is made using the participant's own blood cells. The vaccine will contain a virus called an adenovirus, similar the virus that causes the common cold. The virus has been changed so it cannot infect humans and cause infections. The vaccine will be prepared at Moffitt Cancer Center in the Cell Therapy Laboratory Facility. Conditions: Multiple Myeloma Intervention / Treatment: BIOLOGICAL: Survivin Vaccine, PROCEDURE: Autologous Hematopoietic Cell Transplantation, BIOLOGICAL: Prevnar 13, DRUG: Granulocyte-colony Stimulating Factor Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Screening: * As of protocol Version 2 there is no "screening phase".Patients previously consented to the screening phase could still be eligible for treatment if consented for treatment, based upon the updated eligibility criteria. Treatment: * Patients with histologically confirmed Multiple Myeloma that are being considered for high dose chemotherapy and autologous stem cell transplant. * Patients must have a bone marrow biopsy available, or one scheduled to be performed for a clinical indication so that survivin expression could be determined (note: survivin staining in tumor need not be resulted prior to enrollment or treatment as it is obtained for correlative science). * Patients planned for treatment with high dose melphalan and autologous hematopoietic cell transplant (HCT). * Complete blood count (CBC) with an absolute neutrophil count (ANC) >= 1,000/uL, hemoglobin >= 8.0 g/dL and platelet count >= 50,000/uL. * Liver enzymes: total bilirubin less than or equal to 2 mg/dL (>2 mg/dL permitted if the patient has evidence of Gilbert's disease based upon prior bilirubin elevation or genetic testing); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) less than 1.5 X the upper limit of normal (ULN). * Signed informed consent form in accordance with institutional and federal law policies. Exclusion Criteria: Treatment: * Patients with Complete Response (CR) or stringent CR after induction therapy as defined by International Response Criteria after most recent therapy. * Patients with progressive disease at time of transplant. * Pregnant or lactating woman (as evaluated by serum testing within 48 hours of administration of the first vaccine in women of child bearing potential). * HIV infection confirmed by nucleic acid tests (NAT). * Common variable immunodeficiency. * Active central nervous system (CNS) malignancy. * Active bacterial, fungal or viral infection. * Prior history of allogeneic hematopoietic cell transplantation * Prior malignancy within 5 years of enrollment excluding non-melanoma skin cancer or cervical carcinoma after curative resection, not requiring chemotherapy. * History of severe allergy (e.g., anaphylaxis) to any component of Prevnar or any diphtheria-toxoid containing vaccine.

Study Objectives This phase II/III trial is studying the side effects and how well giving dasatinib together with combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia (ALL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with combination chemotherapy may kill more cancer cells. Conditions: Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 Intervention / Treatment: DRUG: Asparaginase, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Daunorubicin Hydrochloride, DRUG: Dexamethasone, DRUG: Etoposide, BIOLOGICAL: Filgrastim, DRUG: Hydrocortisone Sodium Succinate, DRUG: Ifosfamide, OTHER: Laboratory Biomarker Analysis, DRUG: Leucovorin Calcium, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Methylprednisolone, DRUG: Pegaspargase, DRUG: Prednisone, RADIATION: Radiation Therapy, DRUG: Vincristine Sulfate Location: Canada, New Zealand, United States, Australia, Puerto Rico Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Newly diagnosed acute lymphoblastic leukemia (ALL) * Definitive evidence of BCR-ABL fusion (Philadelphia chromosome positive \[PH+\]) from an approved Children's Oncology Group (COG) cytogenetics laboratory * Meets one of the following criteria: * Concurrent enrollment on Clusters of Orthologous Groups (COG)-AALL03B1 (or a successor trial) AND COG-AALL0232, COG-AALL0331, COG-AALL0434 or other front-line COG ALL clinical trial * Concurrent enrollment on COG-AALL03B1 (or a successor trial) AND scheduled to receive a 3 or 4-drug standard induction regimen * Concurrent enrollment on a Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium trial (or scheduled to be treated as per a DFCI Childhood ALL Consortium induction regimen) * All patients must have definitive evidence of BCR-ABL fusion from an approved COG cytogenetics laboratory; patients may NOT have received Day 15 of Induction chemotherapy (or day 18 vincristine if enrolled on a DFCI Childhood ALL Consortium trial) prior to enrollment on AALL0622 * Patients must have a performance status of 0, 1 or 2 at completion of two weeks of Induction; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age * Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m\^2 or maximum serum creatinine based on age and gender as follows: * 0.4 mg/dL (for patients 1 to 5 months of age) * 0.5 mg/dL (for patients 6 to 11 months of age) * 0.6 mg/dL (for patients 1 year of age) * 0.8 mg/dL (for patients 2 to 5 years of age) * 1.0 mg/dL (for patients 6 to 9 years of age) * 1.2 mg/dL (for patients 10 to 12 years of age) * 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age) * 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age) * Total bilirubin =< 1.5 times upper limit of normal (ULN) for age * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) < 2.5 times ULN for age * Shortening fraction >= 27% by echocardiogram or ejection fraction >= 50% by gated radionuclide study * No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided * Patients will start AALL0622 therapy on day 15 of induction therapy (or day 18 if enrolled on a DFCI Childhood ALL Consortium trial); patients must have received the first 2 weeks of Induction therapy Exclusion Criteria: * Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method * Female patients who are lactating must agree to stop breast-feeding * Patients with Down syndrome * Patients with any clinically significant cardiovascular disease including the following: * Myocardial infarction or ventricular tachyarrhythmia within 6 months * Ejection fraction less than institutional normal * Major conduction abnormality (unless a cardiac pacemaker is present)

Study Objectives The addition of chemotherapy to lung cancer surgery is now considered as the standard of care. Solid data support postoperative chemotherapy but only few results are available in the preoperative setting. To define which timing of perioperative chemotherapy offers the best survival improvement, the IFCT 0002 study is conducted in France. Conditions: Non-small Cell Lung Cancer Stage I and II, Peri-operative Chemotherapy Intervention / Treatment: DRUG: gemcitabine + cisplatine, DRUG: Paclitaxel + Carboplatine Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Histologically or cytologically NSCLC stade I or II Resectable disease WHO performance status of 2 or less Exclusion Criteria: NSCLC stage III or IV

Study Objectives In the United States, the incidence of biliary tract cancer and gallbladder cancer has been estimated to be 6,000-8,000 patients per year. Currently, there is no standard therapy for these tumors once the disease has spread and is inoperable. Recent small studies with gemcitabine have shown a positive response rate. The investigators plan to test the combination of gemcitabine with cisplatin for biliary tract and gallbladder cancers. Conditions: Gallbladder Cancer, Biliary Tract Cancer Intervention / Treatment: DRUG: Gemcitabine, DRUG: Cisplatin 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: * Histologically-confirmed, locally unresectable or metastatic biliary tract (bile ducts, hepatic duct, cystic duct, common bile duct, ampulla of Vater) or gallbladder adenocarcinoma. Patients must have at least one measurable lesion greater than 1 cm, by Response Evaluation Criteria in Solid Tumors (RECIST) criteria outside of prior radiation field. * Zero to one prior chemotherapy for biliary tract or gallbladder cancer. Prior chemoembolization to the liver allowed as long as measurable disease is outside of chemoembolization area and other baseline characteristics are met. No prior gemcitabine or cisplatin therapy allowed. * No chemotherapy within past 3 weeks of initiation of therapy (6 weeks if prior therapy was mitomycin C or nitrosurea) * Chronological age > 18 years. * ECOG performance status 0-2; life expectancy >12 weeks. * Laboratory values: ANC greater than or equal to 1500/mm3; platelets greater than or equal to 100,000/mm3; SGOT and SGPT less than or equal to 3x upper limits of normal (unless liver is involved with tumor, in which case the transaminases must be less than or equal to 5 x upper limits of normal); total bilirubin less than or equal to 2.0 mg/dL. * Creatinine less than or equal to 1.8 mg/dL or creatinine clearance greater than or equal to 50 mL/min * All patients must sign informed consent. * Patients may have prior placement of stents or shunts to relieve obstruction. Exclusion Criteria: * Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis. * Myocardial infarction in the past six months. * Major surgery in the past two weeks. * Uncontrolled serious medical or psychiatric illness. * Women must not be pregnant or lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study. * Patients with concurrent malignancy of any site, except for limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with any other malignancy within 5 years of study entry, except for curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

Study Objectives The purpose of this study is to evaluate the efficacy of S 95005 in patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to standard chemotherapies in terms of Progression-Free Survival rate at 2 months in the Russian population. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: S95005 Location: Russian Federation Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female aged ≥18 years of age * Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum * Has received at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer (including fluoropyrimidines, irinotecan and oxaliplatin and, if accessible, an anti-VEGF monoclonal antibody and at least one of the anti-EGFR monoclonal antibodies for RAS wild-type patients (if RAS mutation status was evaluated)) and was refractory or intolerant to those chemotherapies * Has Eastern Cooperative Group (ECOG) performance status of 0 or 1 * Has at least one measurable metastatic lesion(s) * Has adequate organ function * Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control during the study and for 6 months after the discontinuation of study medication Exclusion Criteria: * Pregnancy, breastfeeding * Participation in another interventional study within 4 weeks prior to inclusion; participation in non-interventional registries or epidemiological studies is allowed * Has previously received S95005 or history of allergic reaction attributed to compounds of similar composition to S95005 * Has a serious illness or medical condition(s) as described in the protocol * Has had certain other recent treatment e.g. major surgery, field radiation, anticancer therapy, within the specified time frames prior to inclusion * Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 attributed to any prior therapies.

Study Objectives This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-lymphocyte activation gene-3 (LAG-3) antibody TSR-033 alone, in combination with the anti-PD-1 antibody dostarlimab, and in combination with dostarlimab, modified folinic acid (FOL)/leucovorin, 5-fluorouracil and oxaliplatin (OX) (mFOLFOX6) or FOL/leucovorin, 5-fluorouracil and irinotecan (IRI) (FOLFIRI), and bevacizumab in participants with advanced solid tumors in a broad range of solid tumors. Participants with disease types selected for evaluation in this study are expected to derive clinical benefit with addition of an anti-PD-1. The study will be conducted in two parts with Part 1 consisting of dose escalation to determine the recommended phase 2 dose (RP2D) of TSR-033 as a single agent (Part 1a) and in combination with dostarlimab (Part 1c). RP2D decisions will be based on the occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), as well as pharmacodynamics (PDy) data. Part 2A of the study will investigate the anti-tumor activity of TSR-033 and dostarlimab in combination in participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC). Part 2B of the study will investigate the safety and anti-tumor activity of TSR-033 and dostarlimab in combination with chemotherapy (Cohort B1: mFOLFOX6 and Cohort B2: FOLFIRI) and bevacizumab in participants with advanced or metastatic MSS-CRC. Conditions: Neoplasms Intervention / Treatment: DRUG: TSR-033, DRUG: Dostarlimab, DRUG: mFOLFOX6, DRUG: FOLFIRI, DRUG: Bevacizumab Location: United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria for participants in Part 1: * The participant is >=18 years of age. * The participant has any histologically or cytologically confirmed advanced (unresectable) or metastatic solid tumor and has PD after treatment with available therapies that are known to confer clinical benefit or who are intolerant to treatment. * The participant must have an archival tumor tissue sample that is formalin-fixed and paraffin-embedded (FFPE) (blocks preferred over slides) and requested and confirmed available from offsite locations prior to dosing. The quality and quantity of the sample must be confirmed sufficient as per the Study Laboratory Manual. Participants who do not have archival tissue must agree to a new biopsy to obtain fresh tumor tissue prior to dosing. * Part 1b (PK/PDy cohort): The participant must have lesions amenable for biopsy and agree to undergo biopsies for fresh tumor tissue prior to treatment, approximately 4 to 6 weeks after treatment, and, whenever possible, at the time of PD and /or end of treatment (EOT). Serial biopsies are optional for participants in Part 1a and 1c. * Female participants must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication if of childbearing potential or be of non-childbearing potential. Non-childbearing potential is defined as: * Participants >=45 years of age and has not had menses for >1 year. * Amenorrheic for <2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation. * Post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure. * Female participants of childbearing potential (that is \[ie\], those who do not meet above criteria) must agree to use 2 highly effective forms of contraception with their partners, starting with the screening visit through 150 days after the last dose of study therapy. * The participant must have an ECOG PS of <=1. * The participant has adequate hematologic and organ function, defined as: * Absolute neutrophil count (ANC) >=1500 per microliter (/μL). * Platelets >=100,000/μL. * Hemoglobin (Hb) >=9 grams per deciliter (g/dL) or >=5.6 millimoles per liter (mmol/L). * Serum creatinine <=1.5 times upper limit of normal (× ULN) or calculated creatinine clearance (CrCL) >=50 milliliters per minute (mL/min) using Cockcroft-Gault equation for participants with creatinine levels >1.5 × institutional ULN * Total bilirubin <=1.5 × ULN and direct bilirubin <=1× ULN (in the event that the total bilirubin result exceeds the upper institutional limits of normal, direct bilirubin will be obtained to determine eligibility). * AST and ALT <=2.5 × ULN unless liver metastases are present, in which case they must be <=5 × ULN. * INR of PT <=1.5 × ULN, unless participant is receiving anticoagulant therapy, then PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants; aPTT) <= 1.5 × ULN unless participant is receiving anticoagulant therapy, then PT or PTT is within therapeutic range of intended use of anticoagulants. Inclusion criteria for participants in Part 2: * The participant is >= 18 years of age. * The participant has any histologically or cytologically confirmed CRC that is metastatic or not amenable to potentially curative resection (advanced), in the opinion of the Investigator. * The participant has a primary and/or metastatic tumor(s) that is known to be MSS, as determined locally. * The participant must have lesions amenable for biopsy and agree to undergo biopsies for fresh tumor tissue prior to treatment, approximately 4 to 6 weeks after, and, whenever possible, at EOT and/or the time of PD. If the participant has had a biopsy prior to entering the 28-day screening period, and within approximately 12 weeks of study treatment, that biopsy sample may be accepted as the Baseline fresh biopsy. Additionally, submission of sufficient high-quality archival tumor tissue is recommended, if available, to enable a longitudinal analysis of tumor biomarkers. * The participant has measurable disease by RECIST v1.1. * The participant has resolution to Grade <=1, per CTCAE v5.0, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy, with the exception of peripheral neuropathy, which must have resolved to Grade <=2, and except where otherwise noted in the eligibility criteria. * Female participants must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication if of childbearing potential or be of non-childbearing potential. Non-childbearing potential is defined as: * Participants >=45 years of age and has not had menses for >1 year. * Amenorrheic for <2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation. * Post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure. * Female participants of childbearing potential (ie, those who do not meet above criteria) must agree to use 2 highly effective forms of contraception with their partners, starting with the screening visit through 150 days after the last dose of study therapy. * The participant has an ECOG PS of <=1. * The participant has adequate hematologic and organ function, defined as: * ANC >=1500/μL. * Platelets >=100,000/μL. * Hb >=9 g/dL or >=5.6 mmol/L. * Serum creatinine <=1.5 × ULN or calculated CrCL >=50 mL/min using Cockcroft-Gault equation for participants with creatinine levels >1.5 × institutional ULN * Total bilirubin <=1.5 × ULN and direct bilirubin <=1× ULN (in the event that the total bilirubin result exceeds the upper institutional limits of normal, direct bilirubin will be obtained to determine eligibility). * AST and ALT <=2.5 × ULN unless liver metastases are present, in which case they must be <=5 × ULN. * INR of PT <=1.5 × ULN, unless participant is receiving anticoagulant therapy, then PT or PTT is within therapeutic range of intended use of anticoagulants; aPTT) <= 1.5 × ULN unless participant is receiving anticoagulant therapy, then PT or PTT is within therapeutic range of intended use of anticoagulants. * Urinary protein is <=1+ on dipstick for routine urinalysis; if urine protein >=2+, a 24-hour urine sample must be collected and must demonstrate <1000 mg of protein in 24 hours to allow participation in the study. * Baseline albumin >=3.0 g/dL. Inclusion Criteria for participants in Part 2A: * The participant must have had at least 2, but no more than 3, prior lines of therapy in the advanced or metastatic setting. Adjuvant chemotherapy with radiographic progression >12 months after the last dose will not be considered a line of therapy. * The participant has progressed on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following: * Fluoropyrimidine. * Oxaliplatin: Participants treated with oxaliplatin in adjuvant setting should have progressed after 12 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease. * Irinotecan. * Participants whose disease is known to be RAS-wild-type must have been treated with cetuximab, panitumumab, or other epidermal growth factor receptor (EGFR) inhibitor for metastatic disease. * Bevacizumab and/or another anti-angiogenic agent. * Previous treatment with regorafenib and/or TAS-102 are allowed in the absence of contraindications and if these agents are available to the participant according to local standards. * The time between a participants's last chemotherapy and enrollment must be <=8 weeks. Inclusion Criteria for participants in Part 2B: * The participant has received <=2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted). Inclusion Criteria for participants in Part 2 Cohort B1: * The participant has received first-line combination therapy consisting of bevacizumab or anti-EGFR antibodies with FOLFIRI and has experienced radiographic progression during or after first-line therapy. Radiographic progression >12 months after the last dose of adjuvant therapy will not be considered a line of therapy. * mFOLFOX6 therapy with bevacizumab is appropriate for the participant and is recommended by the investigator. Inclusion Criteria for participants in Part 2 Cohort B2: * The participant has received first-line combination therapy consisting of bevacizumab or anti-EGFR antibodies with FOLFOX (or variant) and has experienced radiographic progression during or after first-line therapy. Radiographic progression >12 months after the last dose of adjuvant therapy will not be considered a line of therapy. * FOLFIIRI therapy with bevacizumab is appropriate for the participant and is recommended by the investigator. Exclusion Criteria for all participants: * The participant has previously been treated with an anti-LAG-3 antibody. * The participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. * The participant has a known concurrent, serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection requiring systemic therapy, including human immunodeficiency virus (HIV), known active hepatitis B or hepatitis C, active infection, or active autoimmune disease. * The participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study. * The participant has a history of interstitial lung disease. * The participant has not recovered (ie, to Grade <=1 or to Baseline) from radiation- and chemotherapy-induced AEs, has received transfusion of blood products (including platelets or red blood cells), or has received administration of colony stimulating factors (including granulocyte colony-stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug. * The participant is currently participating in an investigational study (therapy or device) or has participated in an investigational study within 4 weeks prior to the first dose of study drug. * The participant has received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days or less than 5 times the half-life of the most recent therapy prior to the first dose of the drug, whichever is shorter. * The participant has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to the first dose of study drug. * The participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders. * The participant has experienced any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 12 months prior to first dose of study drug. * The participant has received a prior autologous or allogeneic organ or transplantation. * The participant has undergone major surgery within 28 days or subcutaneous venous access device placement within 7 days prior to the first dose of study drug. * The participant has had a serious non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of study drug. * The participant has an elective or planned major surgery to be performed during the course of the trial. * The participant has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) in the 12 months prior to the first dose of study drug. * The participant has an acute or subacute bowel obstruction, abdominal fistula, or history of chronic diarrhea which is considered clinically significant, in the opinion of the investigator. * The participant has experienced a Grade >=3 bleeding event within 3 months prior to the first dose of study drug. * The participant has either peptic ulcer disease associated with a bleeding event or known active diverticulitis. * The participant has not recovered (Grade >=1) from AEs and/or complications from any major surgery prior to the first dose of study drug. * The participant has received a vaccine within 7 days of the first dose of study drug. * The participant has known hypersensitivity to TSR-033, dostarlimab (Part 1c and Part 2), or associated excipients. Exclusion Criteria for participants in Part 1: * The participant's prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-LAG-3 agent that resulted in permanent discontinuation due to an AE. Exclusion Criteria for participants in Part 2: * The participant has been previously treated with an anti-PD-1 or anti-PD-L1 antibody. Exclusion Criteria for participants in Part 2B: * The participant has known dihydropyrimidine dehydrogenase deficiency. * The participant experienced an arterial thrombotic/thromboembolic event, Grade 4 hypertension, Grade 4 proteinuria, a Grade 3-4 bleeding event, or bowel perforation during first-line therapy with a bevacizumab-containing regimen. * The participant has known hypersensitivity to bevacizumab, mFOLFOLX6 (Cohort B1) or FOLFIRI (Cohort B2), or associated excipients. * The participant experienced PD within 12 months of last dose of adjuvant therapy.

Study Objectives In this study, BKM120 will be administered to adult patients with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. The trial will confirm the safety and tolerability and determine the maximum tolerated dose (MTD) of BKM120 in Japanese patients. Conditions: Advanced Solid Tumor Intervention / Treatment: DRUG: BKM120 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 with histologically confirmed, advanced unresectable solid tumors who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists. * At least one measurable or non-measurable lesion as defined by RECIST guidelines for solid tumors. * Age ≥ 20 years * Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2 * Life expectancy of ≥ 12 weeks * Patients must have the laboratory values Exclusion Criteria: * Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attribute to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases * Prior treatment with a PI3K inhibitor * Patients with any peripheral neuropathy ≥ CTCAE grade 2 * Patients with unresolved diarrhea ≥ CTCAE grade 2 * Women of child-bearing potential who are pregnant or breast feeding. Men or women of reproductive potential not to sign informed consent for birth control. Barrier contraceptives must be used throughout the trial and six months after the end of treatment. Other protocol-defined inclusion/exclusion criteria may apply

Study Objectives This is a clinical study to evaluate the bioequivalence of dasatinib tablet produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Sprycel® produced by Bristol Myers Squibb after single dose in healthy subjects, so as to provide reference for clinical evaluation and clinical medication; to observe the safety of the dasatinib tablet and the reference drug Sprycel® in healthy subjects under fasting and fed states. Conditions: Leukemia, Myelogenous, Chronic Intervention / Treatment: DRUG: CTTQ Dasatinib tablet, DRUG: Sprycel Dasatinib tablet Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Subjects signed the informed consent form before the trial and fully understood the trial content, process and possible adverse reactions; * Subjects were able to complete the study according to the requirements of the trial protocol; * Subjects have no disease history of heart, liver, kidney, digestive tract, nervous system, mental disorders and metabolic disorders; * Healthy male and female subjects at age of 18-55; * Male subjects weighted ≥ 50 kg, female subjects weighted ≥ 45kg, and the body mass index (BMI) was18 kg/m2 to 28 kg/m2 (including the cutoff value). * Normal or not clinical significant abnormal vital signs, physical examination, laboratory examination, ECG and imaging examination have; * The female blood pregnancy test was negative, and the subjects (including male subjects) had no pregnancy plan from 2 weeks before administration to at least 1 month after the last dose of the study drug and voluntarily took effective contraceptive measures. Exclusion Criteria: * Subjects with the following diseases or with clinically significant abnormalities in clinical laboratory examinations or other clinical findings of clinical significance (including but not limited to gastrointestinal, kidney, liver, neurological, blood, endocrine, tumor, lung, immune, psychiatric, cardiovascular and cerebrovascular diseases); * Subjects with known allergies to dasatinib or its excipients; * Subjects smoked at least 5 cigarettes per day 3 months before screening; * Subjects with a history of drug or alcohol abuse; * Subjects who donated blood within 3 months before screening; * Subjects who took any drugs that could change liver enzyme activity 28 days before taking the study drug; * Subjects who have taken any drugs, vitamin products or herbal medicines within 14 days before clinical trial; * Subjects who smoked and drank alcohol during the trial, or performed strenuous exercise before the trial; * Subjects have taken the study drug and participated in other drug clinical trials within 2 months before the clinical trial; * Subjects with abnormal vital sign results; * Subjects with abnormal clinical medical investigation; * Subjects who had clinically significant ECG abnormalities; * Subjects with abnormal chest X-rays; * Subjects with the positive results of Hepatitis (including hepatitis B and C), AIDS, and syphilis; * Female subjects who were lactating or serum-positive for pregnancy; * Those who screen positive for drugs or have a history of drug abuse in the past five years or have used drugs in the three months prior to the trial; * Subjects with acute illnesses that occurred during the screening period or prior to study drug administration; * Acute disease occurs during pre-study screening stage or before study medication * Subjects with a history of peptic ulcer or intracranial hemorrhage; * Subjects had any disease that increased the risk of bleeding, * Subjects were unable to comply with ward management regulations; * Subjects cannot complete the trial for personal reasons; * Subjects judged unsuitable for participating in this trial by other investigators.

Study Objectives This study is designed to assess the effect of food and antacid use on the pharmacokinetic properties of BIIB021. Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: BIIB021 and Food, DRUG: BIIB0121 and Antacid Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Subjects with histologically or cytologically confirmed solid tumors who have failed or are not candidates for standard therapies or for whom no approved therapy is available. * Eastern Cooperative Oncology Group (ECOG) performance status of greater or equal to 2. * Medically able to tolerate a high fat meal and to fast as per protocol. * Expected survival time of at least 3 months in the opinion of the Investigator. * Ability to take ranitidine as per protocol. * Must be able to swallow and retain oral medication. * Lab values consistent with adequate renal, hepatic, and bone marrow functions. * Electrocardiogram (ECG) with QTc of ≤450 msec for men or ≤470 msec for women and no clinically significant findings. Exclusion Criteria: * Pregnant (positive pregnancy test) or nursing women. * Previous treatment with an Hsp90 inhibitor. * Use of antacids within 7 days of Study Day 1. * Prior antitumor therapies, including prior experimental agents or approved antitumor therapies within 28 days of the first dose of BIIB021. * Major surgery or radiation within 28 days of the first dose of BIIB021. * Uncontrolled, severe medical illness, which in the opinion of the Investigator and/or Sponsor could compromise protocol objectives. * History of gastrectomy or major surgery to small intestine. * History of exocrine pancreatic insufficiency. * Chronic diarrhea (excess of 2 to 3 stools/day above normal frequency). * Active bacterial or viral infection requiring concurrent treatment. * History of hepatitis B or C or human immunodeficiency virus. * History of central nervous system metastasis. * Any thrombotic event occurred <3 months prior to Day 1. * Conditions that may predispose subjects to seizures: History of seizure, previous significant head trauma * Drug or alcohol abuse.

Study Objectives This is an open-label, multicenter, three arm, parallel, randomized, Phase 3 study evaluating the efficacy and safety of S-1 alone compared with S-1 plus CDDP, and S-1 plus CDDP compared with 5-FU plus CDDP in patients with advanced gastric cancer previously untreated with chemotherapy for advanced disease. Patients will be randomly assigned (1:1:1) to S-1 (Arm A), S-1/CDDP (Arm B) or 5-FU/CDDP (Arm C). Patients will be stratified to achieve balanced distribution of patients to each arm according to following stratifications, performance status (0, 1, or 2), the number of metastatic sites (1 vs \>1), prior gastrectomy, and center. Conditions: Gastric Cancer Intervention / Treatment: DRUG: S-1, DRUG: S-1 plus CDDP, DRUG: 5-FU plus CDDP Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Non-prior chemotherapy treated advanced gastric adenocarcinoma * Age 18 and over * Performance status 0, 1, or 2 (ECOG) * Life expectancy 3 months * Hematopoietic WBC lower limit of normal-12,000/mm\^3 Absolute granulocyte count ≥ 2,000/mm\^3 Platelet count ≥ 100,000/mm\^3 Hemoglobin ≥ 8.0 g/dL * Hepatic AST and ALT ≤ 100 U/L ALP ≤ 2 times upper limit of normal (ULN) Bilirubin ≤ 1.5 mg/dL * Renal Plasma creatinine ≤ ULN Creatinine clearance ≥ 60 mL/min Exclusion Criteria: * Interstitial pneumonia, pulmonary fibrosis * Myocardial infarction within the last 6 months, severe/unstable angina, congestive heart failure * Intestinal paralysis, intestinal obstruction, uncontrollable diabetes

Study Objectives In Spain, palbociclib was launched last November 1st, 2017. However, since February 2015 the on-going compassionate use programme of palbociclib has enabled drug access to patients with RH+/HER2- breast cancer previously treated with at least 4 treatment lines for advanced disease. During this period, approximately 400 patients have received treatment within this programme. Since this population of patients more pre-treated was not included in the studies for regulatory submission, the collection of efficacy and toxicity data in the clinical practice setting is of clinical interest. Conditions: Breast Cancer Intervention / Treatment: DRUG: Palbociclib Location: Spain Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with RH+ y HER2- metastatic breast cancer having progressed to at least 4 previous standard treatment lines in the metastatic setting, and are not eligible to receive palbociclib in a clinical trial * Absolute neutrophil count ≥1,500/mm3 (1.5 x 109/L) * Platelet count ≥100,000/mm3 (100 x 109/L) * Haemoglobin ≥9 g/dL * Creatinine ≤1.5 x ULN or creatinine clearance ≥ 60 mL/min * Total bilirubin ≤1.5 x ULN (≤3.0 x ULN in case of Gilbert's disease) * AST and/or ALT ≤3 x ULN (≤5.0 x ULN in case of hepatic metastases) * Alkaline phosphatase ≤2.5 x ULN (≤5.0 x ULN in case of hepatic or bone metastases) Exclusion Criteria: * Major surgery, chemotherapy, radiotherapy, treatment with an investigational drug or any other active anticancer therapy within two weeks of treatment initiation * Previous radiotherapy in ≥25% of bone marrow * QTc >480 msec, personal or family past history of short or long QT syndrome, Brugada's syndrome, or past history of QT interval prolongation, or tachycardia with Torsade de Pointes (TdP) * History of any of the following conditions within 6 months of treatment initiation: myocardial infarction, unstable angina, grade ≥2 arrhythmia (CTCAE version 4.0), atrial fibrillation, coronary or peripheral artery by-pass, symptomatic congestive heart failure, stroke, or pulmonary thromboembolism * Known hypersensitivity to palbociclib * Current or recent suicidal ideation or behaviour

Study Objectives A treatment study is being conducted by the University of Rochester Cancer Center (URCC) in which patients with non-small cell lung cancer will be treated with radiation therapy and a drug called paclitaxel. Paclitaxel is a natural product with anticancer properties. The first purpose of this study is to determine the dose of paclitaxel which, when given in combination with radiation therapy, will provide the greatest effect have the least side effects. To determine this, patients will be put on the study in groups of 3. The dose for each additional group will be higher than the previous dose until the maximum tolerated dose is reached. The second purpose is to determine if radiation therapy with paclitaxel is more effective in treating lung cancer than radiation therapy alone. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Paclitaxel, PROCEDURE: Radiation Therapy 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: * Histologically confirmed lung cancer, excluding small cell carcinoma * Inoperable stage I (T1-2N0) and II (T1-2N1, T3N0) disease, or stage IIIA (T3N1 andT1-3N2M0) and IIIB (TxN3M0, T4NxM0) diseases according to the American Joint Committee of Cancer criteria 1998 * The primary tumor must be radiographically measurable. * Age > 18. * Karnofsky performance status > 70. * FEV1 sufficient for patients to tolerate radiation therapy which is at the discretion of the radiation oncologist, usually > 800 ml * Labs: WBC > 3000; platelet count > 100,000; serum creatinine < 1.5 mg/dl or creatinine clearance >60 ml/min. * Laboratory values must be obtained < 3 weeks prior to registration. * A signed informed consent. * Patients who failed prior chemotherapy are eligible. Patients with prior radiotherapy to the chest region are eligible as long as the normal tissue tolerance is not violated by repeat radiotherapy. Exclusion Criteria: * Patients with medical contraindication to chemotherapy or radiotherapy. * Patients with myocardial infarction within the preceding six months or symptomatic heart disease, including uncontrolled or unstable angina, uncontrolled congestive heart failure, and uncontrolled arrhythmia. * Women who are pregnant. * Patients with small cell carcinoma or mesothelioma

Study Objectives The purpose of this study is to determine if MDX-1203 is safe for the treatment of renal cell carcinoma or non-hodgkin's lymphoma. Conditions: Renal Cell Carcinoma, Non-hodgkin's Lymphoma Intervention / Treatment: BIOLOGICAL: MDX-1203 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: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 * Criteria specific to each tumor type: * For Clear cell renal cell carcinoma (ccRCC): advanced or recurrent disease. Must have failed at least 1 prior systemic therapy * For B-cell non-Hodgkin's lymphoma (B-NHL): Must have failed at least 1 prior systemic therapy * Measurable disease criteria by tumor type: * For ccRCC: At least 1 unidimensional measurable lesion * For B-NHL: At least 1 bidimensionally measurable lesion * Prior therapies for advanced/recurrent ccRCC or relapsed/refractory B-NHL or have become intolerant to a systemic therapy * Provide archived or fresh tumor tissue for CD70 status. Subjects must be CD70+ * Provision of fresh tissue (pre-treatment and on-treatment) for exploratory analysis is mandatory for at least 5 and a maximum of 10 B-NHL subjects Exclusion Criteria: * Prior therapy with an anti-CD70 antibody * History of severe hypersensitivity reactions to other monoclonal antibodies * Active or untreated central nervous system lymphoma * Active infection (viral, bacterial, or fungal) * Evidence of bleeding diathesis or coagulopathy * Active autoimmune disease requiring immunosuppressive therapy * Known current drug or alcohol abuse

Study Objectives Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis. This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer. Conditions: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women Intervention / Treatment: DRUG: Letrozole, DRUG: Tamoxifen Location: Denmark, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria * Female * Post-menopausal hormone status defined as: * Patients with menostasis (amenorrhea) > 12 months or history of oophorectomy. * Patients ≥ 55 years with history of hysterectomy or having continued/renewed menstruation on cyclic hormone treatment. * Patients of 50-54 years: Menopausal status was determined on the basis of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values. * Histologically confirmed resected breast cancer and eligible for adjuvant endocrine therapy. As a minimum, patients had to have receptor-positive tumors, which were defined either as estrogen receptor (ER) and/or progesterone receptor (PgR) ≥ 10 fmol/mg cytosol protein; or ≥ 10% of the tumor cells positive by immunocytochemical evaluation. * Adequate bone marrow function (white blood cell count \[WBC\] > 3.0 x 109 /L, platelets ≥ 100.0 x 109 /L, and hemoglobin > 10 g/dL). * Documented evidence of adequate renal function (creatinine < 180 µmol/L) and hepatic function (bilirubin < 30 µmol/L, alanine aminotransferase (ALT) < 1.5 x upper normal limit of the laboratory). * Life expectancy of at least 24 months at the time of enrollment. * Written voluntary informed consent prior to initiation of any study procedure. * Willingness to undergo all scheduled tests and examinations for evaluation of bone density and bone metabolism, and lipid profiles in addition to the standard assessments for monitoring their breast cancer status. Exclusion Criteria * Patients with distant metastases as defined by the criteria of the Danish Breast Cancer Co-operative Group (DBCCOG). * Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget's disease). * Patients receiving bisphosphonates for more than 3 months before randomization. * Chronic treatment with drugs known to interfere with bone metabolism, e.g. * Anti-convulsants within the past year. * Corticosteroids at doses greater than the equivalent of 5 mg/day prednisone for more than two weeks in the past 6 months (prior to randomization). * Any previous treatment with sodium fluoride at daily doses ≥ 5 mg/day for a period exceeding 1 month. * Anabolic steroids in the past 12 months. * Long term use of coumarin derivatives and heparin at the time of randomization. * Metabolic diseases known to interfere with bone metabolism (e.g., Hyperparathyroidism, hypoparathyroidism, uncontrolled thyroid disease, Cushing's disease, vitamin D deficiency, malabsorption syndrome, etc.). * Treatment with lipid-lowering agents within the 3 months prior to randomization (this exclusion criterion did not apply to patients randomized in the United Kingdom). * Patients receiving other anti-cancer treatment. * Previous neoadjuvant / adjuvant chemotherapy and /or previous adjuvant endocrine therapy (e.g., anti-estrogens, AIs). * History of previous or concomitant malignancy within the past 5 years other than adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who had a previous other malignancy must have been disease free for five years. Patients with endometrial cancer and/or invasive breast cancer at any time in their medical history were excluded. Patients with invasive bilateral breast cancer were excluded. Patients with vaginal discharge/ vaginal bleeding with evidence of malignancy were excluded. * Any other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.

Study Objectives The rationale of this study is to investigate the effects of topical diclofenac on tumor metabolism in the treatment of actinic keratoses in immunocompetent and immunocompromised patients. Study hypothesis is that topical diclofenac lowers lactate level in skin biopsies of actinic keratoses. Planned number of patients is 38. This study is a monocenter study investigating the effects of 3% diclofenac in 2.5% hyaluronic acid gel on tumor metabolism in the treatment of actinic keratoses. Treatment duration is 3 months. Skin biopsies will be obtained before treatment, at the end of the treatment and four weeks after the treatment. Control biopsies at visit 1 and 3 are performed in healthy, sun damaged and untreated skin. Evaluation of efficacy will be performed at the end of the treatment and four weeks after the treatment. Duration of treatment is 3 months (±4 weeks). Approximately 0,5g Solaraze® 3% gel is applied on a 5cm x 5cm lesion. Solaraze® 3% gel is applied twice daily on the study lesions. Conditions: Actinic Keratoses Intervention / Treatment: DRUG: 3% diclofenac in 2.5% hyaluronic acid gel Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: BASIC_SCIENCE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written informed consent has been signed prior to or at Screening Visit * Caucasian male and female patients * Age > 18 years * Negative pregnancy test in women of childbearing age * Clinical diagnosis of actinic keratosis (AK) * A minimum of three AK lesions Exclusion Criteria in immunocompromised patients : * Concomitant UV-phototherapy * Pregnancy or lactation * Women in child-bearing age who do not use highly efficient contraceptive methods (<1% failure rate per year) * Skin diseases that might interfere with response evaluation of study treatment * Topical pretreatment of the AK study lesions with photodynamic therapy, Solaraze® 3% gel, Aldara®, 5-FU, or polyphenon E during the 8 weeks preceding study treatment * Radiation therapy performed in the treatment area during the 3 months preceding study therapy * Systemic treatment with diclofenac * Known intolerance to diclofenac or to any other ingredient of Solaraze® 3% gel * Conditions that might interfere with the ability to understand the study and thus give written informed consent * Simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding inclusion * Suspected lack of compliance Exclusion criteria in immunocompetent patients: * Concomitant UV-phototherapy * Pregnancy or lactation * Women in child-bearing age who do not use highly efficient contraceptive methods (<1% failure rate per year) * Patients with clinically relevant suppression of the immune system (e.g. drug induced, infection) * Skin diseases that might interfere with response evaluation of study treatment * Topical pretreatment of the AK study lesions with photodynamic therapy, Aldara®, Solaraze® 3% gel , 5-FU, or polyphenon E during the 8 weeks preceding study treatment * Systemic treatment with cytostatic drugs or radiation therapy performed in the treatment area during the 3 months preceding study therapy * Systemic treatment with diclofenac * Known intolerance to diclofenac or to any other ingredient of Solaraze® 3% gel * Conditions that might interfere with the ability to understand the study and thus give written informed consent * Simultaneous participation in another clinical study or participation in another clinical study in participation in another clinical study in the 30 days directly preceding inclusion * Suspected lack of compliance

Study Objectives This is a prospective open-label one-arm phase III trial designed to evaluate the safety and efficacy of letrozole 2.5 mg administered orally daily for 24 months as adjuvant therapy in postmenopausal patients with primary breast cancer. This trial is not recruiting patients in the United States. Conditions: Breast Cancer Intervention / Treatment: DRUG: Letrozole Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Compliant postmenopausal women with primary operable breast cancer after complete surgery and suitable for endocrine treatment * Nodal status negative or positive * Good Health status 0-2 (Eastern Cooperative Oncology Group) * Estrogen- and/or progesterone-receptor positive * Adequate marrow, kidney and liver function Exclusion criteria: * Metastatic or inflammatory breast cancer * Patients with previous or concomitant cancers (not breast cancer) within the past 5 years EXCEPT adequately treated basal or squamous cell skin cancer or in situ cancer of the cervix. Patients with other previous cancers must have been disease-free for at least 5 years and Patients with uncontrolled, non-malignant systemic cardiovascular, kidney, and liver diseases. * Current/active dental problems including infection of the teeth or jawbone, dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures. * Recent (within 6 weeks) or planned dental or jaw surgery * Patients with primary overactive parathyroid * Patients with a known hypersensitivity to zoledronic acid or other bisphosphonates.

Study Objectives The objective of this study is to evaluate the efficacy and safety of treatment with talimogene laherparepvec compared to subcutaneously administered GM-CSF in patients with unresectable Stage IIIb, IIIc and Stage IV melanoma. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to GM-CSF. Conditions: Melanoma Intervention / Treatment: BIOLOGICAL: Talimogene laherparepvec, BIOLOGICAL: GM-CSF Location: United States, South Africa, United Kingdom, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Males or females age ≥ 18 years * Stage IIIb, IIIc or stage IV disease that is not surgically resectable * Injectable disease (i.e. suitable for direct injection or through the use of ultrasound guidance) * At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion >= 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of >= 10 mm * Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Prolongation in International Normalized Ratio (INR), Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) when the result is from therapeutic anticoagulation treatment are permitted for patients whose injectable lesions are cutaneous and/or subcutaneous such that direct pressure could be applied in the event of excessive bleeding Exclusion Criteria: * Clinically active cerebral or any bone metastases. Patients with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, gammaknife therapy, with no evidence of progression, and have not required steroids, for at least two (2) months prior to randomization * Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For patients with < 3 visceral metastases, no lesion > 3 cm, and liver lesions must meet Response Evaluation Criteria In Solid Tumors (RECIST) criteria for stable disease for at least 1 month prior to randomization

Study Objectives Tapestry Pharmaceuticals, Inc. has developed a novel taxane analog, TPI 287. TPI 287 is synthetically manufactured from naturally occurring taxanes extracted from yew starting material. The synthesis involves modification to the taxane side chain to overcome multidrug resistance and to achieve mutant tubulin binding. This study will be a multi-center, dose escalation, sequential group, phase I study evaluating the intravenous administration of TPI 287, a novel third generation taxane. Conditions: Neoplasms, Non-Hodgkin Lymphoma, Hodgkin Disease Intervention / Treatment: DRUG: TPI 287 Injection 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: * Histological or cytological evidence of malignancy * Patients must have either: * advanced solid tumors that have recurred or progressed following standard therapy, or * Hodgkin's or non-Hodgkin's lymphoma that has recurred or progressed following standard therapy, have not had a previous bone marrow transplant, and are not eligible for a bone marrow transplant. * Failed at least one previous therapeutic regimen and either no longer are candidates for standard therapy, have no standard therapy available, or choose not to pursue standard therapy. * Ambulatory with ECOG 0 or 1, and a life expectancy of >3 months. * Judged by the investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits. * Have ability to read, understand and provide written informed consent for the initiation of any study related procedures or have a legal representative to perform this function. * If female, must have a negative pregnancy test within 21 days of start of treatment. * Agree to the use of an effective method of contraception during the study and for 90 days following the last dose of medication. * Patients with prior radiation therapy for brain metastasis or primary brain tumors are acceptable. Exclusion Criteria: * Prior radiation therapy or chemotherapy within 4 weeks (6 weeks for prior nitrosoureas or mitomycin) * Another active medical condition(s) or organ disease(s) that may either compromise patient safety or interfere with the safety and/or outcome evaluation of the study drug. While this exclusion is not limited to the following abnormalities, if any of the following laboratory abnormalities are present, the patient should be excluded: * WBC < 3000/uL; * Absolute neutrophil count < 1500/uL; * Platelets < 100,000/uL; * Total bilirubin > 1.5 x upper limit of normal; * ALT or AST > 3 x upper limit of normal if no liver metastases or >5 upper limit of normal in the presence of liver metastases; * Serum creatinine > 1.5 x upper limit of normal; * INR >2.0. * Patient has clinically significant cardiac co-morbidities or pulmonary impairment * Patient or physician plans concomitant chemotherapy, radiation therapy, hormonal and/or biological treatment for cancer including immunotherapy while on study. Of note, therapy with LHRH for prostate cancer is acceptable. * Patient has been treated with any investigational drug, investigational biologic, or investigational therapeutic device within 30 days of initiating study treatment. * Tumor appears to involve a major artery or vein. * Prior or concurrent significant CNS disease including stroke, except for primary or secondary malignancies. * Less than 4 weeks since prior major surgery * Known positive for HIV, Hepatitis B or C * Concurrent chronic use of aspirin (325 mg/day or more) * Concurrent or recent (within 1 month) use of thrombolytic agents, or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters) Of note, therapy with low-molecular weight heparin is acceptable as long as the INR<2.0. * Uncontrolled hypertension * Grade II-IV peripheral vascular disease within the past year * Prior allergic reactions to compounds of similar chemical or biologic composition to TPI 287, paclitaxel or taxotere, Cremophor-EL-P, or other study agents * Significant traumatic injury within the past 4 weeks * Ongoing or active infection requiring parenteral antibiotics or with a fever >38.1°C within 3 days of the first scheduled day of dosing * Other concurrent uncontrolled illness which may interfere with the ability of the patient to participate in the trial * Patients who are inpatients * Grade II-IV peripheral neuropathy

Study Objectives Many types of cancer are primarily treated with surgery and patient survival is directly related to the extent to which the tumor is able to be removed. It is often difficult for surgeons to distinguish tumor tissue from normal tissue or to detect tumor cells that have spread from the original tumor site, resulting in incomplete removal of the tumor and reduced patient survival. In some sites, such as the brain, it is critical to avoid damage to normal tissue around the tumor to prevent adverse effects of surgery on function. Tozuleristide is a drug that is thought to attach to tumor tissue and then fluoresces (glows) when a special light from the Canvas is shined on it. It is hypothesized that tozuleristide, when imaged with the Canvas, will improve surgical outcomes by allowing surgeons to visualize the edges of the tumor or other ambiguous tissue in real-time as they operate. The purpose of this study is to evaluate how well tozuleristide imaged with Canvas work at helping to distinguish between tumor and normal tissue during surgery in pediatric primary central nervous system tumors. Conditions: Pediatric Central Nervous System Tumor Intervention / Treatment: DRUG: tozuleristide, DEVICE: Canvas System Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Subjects must be >1 month and ≤30 years of age at the time of study enrollment * Subjects must have MRI obtained within 30 days of study enrollment documenting a measurable lesion consistent with a pediatric primary CNS tumor for which maximal safe resection is indicated * Adequate renal function * Adequate liver function * Prior therapy: Subjects with prior therapy are eligible provided they have recovered from any acute toxic effects of prior therapy and have sufficient time interval prior to enrollment: 1. Radiation therapy: subjects may not have had radiation therapy to the area of tumor planned to be resected within 28 days of study enrollment 2. Chemotherapy: at least 14 days from any myelosuppressive chemotherapy (28 days if prior nitrosourea) and if prior chemotherapy, must have an absolute neutrophil count recovery of ≥ 1000/mm3 following count nadir 3. Biologic: at least 7 days from any anti-neoplastic biologic agent (at least 3 half-lives since last administration of monoclonal antibodies) 4. Immunotherapy: at least 42 days after completion of any cellular immunotherapy, such as CAR-T cell therapy 5. Prior surgery for CNS tumors is allowed 6. Prior tozuleristide: at least 1 week after prior dose of tozuleristide if previously treated * Written informed consent must be obtained from the subject or parent or legal guardian prior to the conduct of study activities. Routine clinical tests, e.g., MRI, clinical laboratory studies, may be used for screening requirements. Assent, when appropriate, will be obtained according to institutional guidelines. * The risks of treatment with tozuleristide during pregnancy have not been evaluated. Female subjects of child-bearing potential must agree not to attempt to become pregnant or undergo in vitro fertilization and, if participating in sexual activity that could lead to pregnancy, must use 2 reliable methods of contraception simultaneously for 30 days after surgery. Male subjects must agree not to attempt to father a child and, if participating in sexual activity that could lead to pregnancy, must use 2 reliable methods of contraception simultaneously for 30 days after surgery if their partner is of child-bearing potential. Exclusion Criteria: * Pregnancy and contraception: Subjects who are pregnant or breast-feeding or planning to conceive a child within 30 days are not eligible. Males and females of childbearing potential must agree to use 2 effective forms of contraception from the time of enrollment until 30 days post-surgery * Subjects with on-going serious medical conditions (poorly controlled asthma, diabetes, heart disease) such that participation in the study could put the subject at increased risk of worsening their condition * Subjects planned to undergo only a diagnostic biopsy procedure, without intent to resect tissue for therapeutic purposes (e.g., stereotactic pontine biopsy) * Subjects who in the opinion of the investigator are not willing or able to comply with randomization procedures or other study-required study procedures and observations. Subjects previously enrolled and randomized to Arm 1 (control) are not eligible for re-enrollment unless a second surgery is required by standard of care.

Study Objectives A randomized, multi-centre trial was conducted between 2013-2016, including 128 patients with untreated CLL from eight hematological clinics in Sweden. Vaccination with polysaccharide pneumococcal vaccine (PPSV23) or conjugated pneumococcal vaccine (PCV13) was performed and the results were published 2018. PCV13 showed a superior immune response, measured as OPA (opsonophagocytic assays) and ELISA (enzyme-linked immunosorbent assay), compared to PPSV23. Immune cells analyses after primary immunization will be performed. Between 2019-2021 a prospective follow up study was conducted of the same cohort and also included a control group. The study participants have been revaccinated with pneumococcal vaccines with the aim to evaluate the effect of repeated dose of PCV13. The antibody response (measured as titer with FMIA (fluorescent multiplexed bead-based immunoassay) and antibody function with MOPA (multiplexed opsonophagocytic assay) will be performed. Studies investigating the dynamics of immune cells before and after primary immunization and revaccination will be performed. The study will give important answers about the optimal vaccination strategy in patients with CLL and can improve the vaccination recommendations in immunocompromised patients. Conditions: CLL, Vaccine Response Intervention / Treatment: BIOLOGICAL: PCV13, BIOLOGICAL: PPSV23 Location: Sweden Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: CLL patients earlier included in the Pneumococcal vaccination study 0887x1-20003 (EudraCT No: 2009-012642-22), who have received either PCV13 or PPSV23 are eligible for evaluation Exclusion Criteria: * Patients receiving high dose corticosteroids ( ≥20 mg Prednisolone) or other immunosuppressive drugs that is not part of active CLL treatment (criteria for inclusion after discontinuing high dose corticosteroid treatment, see section 7.3) * Patients who have had an allergic reaction to any vaccination in the past * Patients with a positive DAT (Direct Antiglobulin Test) or known present or previous hemolysis, ITP (immune thrombocytopenia) and Guillain-Barre * Patients failing to give informed consent * Patients with ongoing immunoglobulin therapy * Patients with known HIV infection * Patients who have received a pneumococcal vaccine outside the study protocol within the last 12 months * Active febrile infection * Increased bleeding risk due to severe thrombocytopenia or other coagulopathies that would, in the opinion of the investigator, contraindicate intramuscular injection (for treatment with oral anticoagulation therapy, see section 7.3) -

Study Objectives Pemetrexed has demonstrated a favorable response with minimal toxicity when used as single agent as first-line and second-line treatment for advanced urothelial carcinoma. The response rates were 32% and 28% for the first-line and second-line setting, respectively. Cisplatin is one the most active chemotherapeutic agents in urothelial cancer, frequently used as combination chemotherapy such as GP (gemcitabine plus cisplatin) or MVAC (methotrexate, vinblastine, adriamycin, and cisplatin). Pemetrexed and cisplatin showed favorable activity profile in advanced non-small cell lung cancer with highly favorable toxicity profile. This study is to assess the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. Conditions: Urothelial Carcinoma Intervention / Treatment: DRUG: Pemetrexed, DRUG: Cisplatin, DRUG: Dexamethasone, DRUG: Vitamins Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic or cytologic diagnosis of urothelial (transitional cell) carcinoma with the exception of micropapillary subtype * Patients must have recurrent disease (locally advanced or metastatic) that is not amenable to local therapy or newly diagnosed distant metastatic disease * Measurable disease defined by RECIST v.1.0 * ECOG performance status of 2 or better * Adequate organ and bone marrow function defined as Exclusion Criteria: * Other tumor type than urothelial carcinoma * Presence or history of CNS metastasis * Prior systemic chemotherapy or immunotherapy (but prior local intravesical chemotherapy or immunotherapy was allowed. And recurrent disease after adjuvant or neoadjuvant cisplatin-based systemic chemotherapy is allowed if the last chemotherapy was administered 1 year or more before the patient enrollment.) * Presence of second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) * Peripheral sensory neuropathy grade 2 or worse * Other serious illness or medical conditions

Study Objectives This phase II trial is studying how well cinacalcet hydrochloride works in treating men with recurrent prostate cancer. Cinacalcet hydrochloride may be effective in lowering prostate-specific antigen (PSA) levels in patients with recurrent prostate cancer that has not responded to previous treatment Conditions: Adenocarcinoma of the Prostate, Recurrent Prostate Cancer Intervention / Treatment: OTHER: laboratory biomarker analysis, PROCEDURE: quality-of-life assessment, OTHER: questionnaire administration, DRUG: cinacalcet hydrochloride 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 histologically or cytologically confirmed adenocarcinoma of the prostate * For patients who have recurrent disease following surgery as first line therapy ("surgical failures") * PSA requirement is 0.2 ng/ml or above * For patients who have recurrent disease following radiation as first line therapy, the eligibility follows the "Phoenix criteria", that is, a rise of 2 ng/mL over the PSA nadir * Eastern Cooperative Oncology Group (ECOG) performance status =< 2 * Granulocytes >= 1000/uL * Serum creatinine =< 2.0 mg/dl * Total serum calcium > 9.0 and < 10.5 mg/dl * Total bilirubin =< 2.0 mg/dl * Platelet count >=100,000/uL * Hemoglobin (Hgb) >= 9 g/dL * Total testosterone >= 50 ng/dL * Ability to understand and the willingness to sign a written informed consent document (either directly or via a legally authorized representative) Exclusion Criteria: * Serious medical illness which would limit survival to less than 3 months * Active, uncontrolled bacterial, viral or fungal infection * Hemorrhagic disorder * Any radiographic evidence of metastatic disease including positive bone scan or computed tomography (CT) abdomen/pelvis * History of hypocalcemia or seizure disorder * Patients with known hypersensitivity to any of the components of cinacalcet (cinacalcet hydrochloride)

Study Objectives This study evaluates addition of Vincristine Sulfate Liposome Injection (Marqibo®) to the standard regimen of Bendamustine and Rituximab in adult patients with indolent B-cell lymphoma. This is a dose-escalation study. Conditions: Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Small-Cell, Waldenstrom Macroglobulinemia, Lymphoma, B-Cell, Marginal Zone Intervention / Treatment: DRUG: Rituximab, DRUG: Bendamustine, DRUG: Vincristine sulfate liposome injection Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Histologically confirmed indolent B-cell non-Hodgkin lymphoma. * Radiological measurable disease. * Previous treatment for lymphoma is allowed, with the exception of use of bendamustine within 6 months or any prior use of vincristine sulfate liposome injection * Eastern Cooperative Oncology Group performance status 0 or 1; * Life expectancy of at least 6 months; * Adequate organ and marrow function; * Women of child-bearing potential and men must agree to use adequate contraception. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * History of allergic reactions attributed to any drug used in the study. * Any lymphoma-directed therapy within 4 weeks. * Any prior treatment with vincristine sulfate liposome injection. * Prior treatment with bendamustine or vincristine sulfate within 180 days of enrollment. * Patients who are receiving any other investigational agents with the exception of endocrine therapy for breast or prostate cancer. * Central nervous system involvement. * Peripheral sensory or motor neuropathy. * History of a demyelinating condition. * Positive test for the Human Anti-Chimeric Antibody (HACA). * Patients receiving any medications or substances that are strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) enzyme are ineligible. * Uncontrolled intercurrent illness. * Prisoners. * Pregnant or breast-feeding women. * Known Human Immunodeficiency Virus (HIV) or active Hepatitis B infection * Any prior or active cancer, which in the opinion of the investigator would preclude safe participation in this study.

Study Objectives This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated). Conditions: Kidney Cancer Metastatic, Kidney Cancer, Kidney Cancer, Stage IV Intervention / Treatment: DRUG: Nivolumab/Ipilimumab, RADIATION: SBRT 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: * Histological confirmation of RCC with a clear-cell component * Metastatic (AJCC Stage IV) RCC * Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred = or > 6 months after the last dose of the adjuvant or neoadjuvant therapy * Any number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mammalian target of rapamycin (mTOR) inhibitor or clinical trial) including previously untreated patients * Karnofsky Performance Status (KPS) of at least 70% * Life expectancy of at least 3 months * At least 2 metastatic sites of which at least 1 must be measurable as per RECIST 1.1 * Archival Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for correlative studies (Note: Fine Needle Aspiration (FNA) and bone metastases samples are not acceptable for submission) * Patients with favorable, intermediate and poor risk categories will be eligible for the study. Patients must be categorized according to favorable versus intermediate/poor risk status at registration. International Metastatic RCC Database Consortium (IMDC) must be used to determine prognostic factors Exclusion Criteria: * Subjects with previously treated brain or CNS (Central nervous system) metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to study drug administration. Liver metastases will not be included as part of the radiated lesions to be treated. Medical History and Concurrent Diseases: * Prior treatment with an anti-Programmed cell death(PD) -1, anti-PD-L1, anti-PD-L2, anti-CD137(cluster of differentiation), or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein ) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Prior treatment with high dose interleukin (HD IL)-2 is allowed. * Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Patients with psoriasis not requiring active, systemic treatment are allowed. * Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease * Uncontrolled adrenal insufficiency * Requirement for anti-coagulation with Coumadin, low molecular weight heparin and anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at least 4 weeks and no recent history of prior bleeding complications. * Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk Gleason 6 prostate cancer * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection * Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results * Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug * Anti-cancer therapy less than 14 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug * Presence of any toxicities attributed to prior anti-cancer therapy, other than alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before administration of study drug Physical and Laboratory Test Findings: * Any of the following laboratory test findings: * White blood cell (WBC) < 2,000/mm3 * Neutrophils < 1,500/mm3 * Platelets < 100,000/mm3 * aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN (> 5 x ULN if liver metastases are present) * Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) * Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance < 40 mL/min (measured or calculated by Cockroft-Gault formula) Allergies and Adverse Drug Reaction: * History of severe hypersensitivity reaction to any monoclonal antibody or study drug components Other Exclusion Criteria: * Prisoners or subject who are involuntarily incarcerated * Not suitable for SBRT treatment * Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness

Study Objectives The primary working hypothesis is that preoperative chemo-sensitivity testing using fluorodeoxyglucose positron emission tomography (FDG-PET) performed before and after one course of FOLFOX (folinic acid, fluorouracil, oxaliplatin) can identify the patients that will least likely have a significant benefit from adjuvant FOLFOX for stage III colon cancer. The benefit will be analyzed by correlating the preoperative FDG-PET uptake changes to the disease free and overall survival. Conditions: Colon Cancer Intervention / Treatment: DRUG: FOLFOX Location: Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age 18 years or older * Clinical/radiological evaluation compatible with stage III colon adenocarcinoma * No prior chemotherapy * No prior abdominal or pelvic irradiation * WHO performance status 0 or 1 * Effective contraception during the study and the following six months * Signed informed consent obtained prior to any study-specific screening procedures * Tumour considered as curatively resectable (R0) based on standard preoperative evaluations * White blood cell count ≥ 3×109/L with neutrophils ≥ 1.5×109/L, platelet count ≥ 100×109/L, haemoglobin ≥ 9 g/dL (5.6 mmol/L) * Direct bilirubin ≤ 1.5×ULN; ASAT and ALAT ≤ 2.5×ULN; Alkaline phosphatase ≤ 2.5×ULN; Serum creatinine ≤ 1.5×ULN * Delay between assessment of screening criteria and first PET/CT < 21 days * Blood glucose < 150 mg/dl at the time of FDG administration. Insulin or oral anti-diabetic medication is not allowed on the days of PET/CT imaging. * Compliance to the first chemotherapy course to be administered before surgery * Delay between the first PET/CT imaging and the start of neoadjuvant FOLOFX < 7 days * Second PET/CT imaging performed on D14 (range: D13-D15, with D1 as the first day of chemo administration) * Delay between the second PET/CT and surgery < 7 days * Stage III (ypTNM) as assessed after surgery * CEA < 1.5 x ULN 1 month after surgery - Exclusion Criteria: * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to screening. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study * Any suspicion of metastatic disease * Rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery * Inflammatory bowel disease * Pregnancy (absence to be confirmed by ß-hCG blood test) or breast-feeding * History or current central nervous system disease or peripheral neuropathy * Hypersensitivity to any of the components of study treatments * Previous malignancy in the last five years except basal-cell carcinoma of the skin or in situ cervical carcinoma * Clinically relevant coronary artery disease or history of myocardial infarction in the last 6 weeks or high risk of uncontrolled arrhythmia * Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent * Any significant disease which, in the investigator's opinion, would exclude the patient from the study

Study Objectives The goal of this clinical research study is to find out if Caphosol® (calcium phosphate) mouthwash is more effective than a baking soda solution at preventing and treating mucositis, in patients with sarcoma who are to be treated with chemotherapy. The safety of this drug will also be studied. Researchers also want to learn about the way calcium phosphate may affect mucous membranes. The goal of this clinical research study is to see if Caphosol® (calcium phosphate) mouthwash is better than baking soda solution in patients with sarcoma who are to be treated with chemotherapy . Caphosol will also be studied to see if it lessens the incidence and severity of oral mucositis (painful sores in the mouth). Conditions: Sarcoma, Oral Mucositis Intervention / Treatment: OTHER: Caphosol, OTHER: Baking Soda Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with high dose doxorubicin (75-90 mg/m\^2) with ifosfamide (AI) or cisplatin (AP) is indicated. * Must be >16 and < 65 years of age. * Females of childbearing potential (defined as not post-menopausal for 12 months, or no previous surgical sterilization) must have a negative blood pregnancy test. * Male and Females of child bearing potential must use acceptable methods of birth control which include oral contraceptives, spermicide with either a condom, diaphragm or cervical cap, us of a intrauterine device (IUD) or abstinence. * Adequate hematologic (ANC > 1500/mm\^3, platelet count > 150,000/mm\^3), renal (serum creatinine < 1.5mg/dL), hepatic (serum bilirubin count < 1.5 x normal and SGPT <3 x normal) functions. * Karnofsky Performance Status >= 80% * Signed informed consent form. Exclusion Criteria: * Pregnant or lactating women. * Patients with any co-morbid condition which renders patients at high risk of treatment complication. * Patient has uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia or hypertension, acute myocardial infarction within 3 months * Patient has an active seizure disorder. (Patients with a previous history of seizure disorders will be eligible for the study, if they have had no evidence of seizure activity, and they have been free of antiseizure medication for the previous 5 years.) * Prior surgery or radiotherapy (RT) within 2 weeks of study entry. * Psychological, social, familial, or geographical reasons that would prevent scheduled visits and follow-up.

Study Objectives This research study is studying Daratumumab as a possible treatment for Waldenström Macroglobulinemia. Conditions: Waldenström Macroglobulinemia Intervention / Treatment: DRUG: Daratumumab 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: * Clinicopathological diagnosis of Waldenström Macroglobulinemia (Owen et al. 2003), and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia (Kyle et al. 2003) * At least one previous treatment for WM with either documented disease progression or no response (stable disease) to the most recent treatment regimen * Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of >2 times the upper limit of normal of each institution is required * Participants with symptomatic hyperviscosity or serum IgM >5,000 mg/dL to undergo plasmapheresis prior to treatment initiation * Age ≥18 years * ECOG performance status ≤2 (see Appendix A) * Participants must have preserved organ and marrow function as defined below: * Absolute neutrophil count ≥ 1,000/mcL * Platelets ≥ 50,000/mcL * Hemoglobin ≥ 8 g/dL * Total bilirubin ≤ 1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease * AST/ALT ≤ 2.5 × institutional upper limit of normal * EGFR ≥ 30 ml/min * Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin. * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 90 days after discontinuation from the study. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. FCBP must be referred to a qualified provider of contraceptive methods if needed. FCBP must have a negative serum pregnancy test at screening. * Able to adhere to the study visit schedule and other protocol requirements. * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent study participation. * Concurrent use of any other anti-cancer agents or treatments or any other investigational agents. * Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Known CNS lymphoma. * New York Heart Association classification III or IV heart failure. * Known history of Human Immunodeficiency Virus (HIV), active infection with Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV). * Lactating or pregnant women. * Grade >2 toxicity (other than alopecia) continuing from prior anti-cancer therapy. * History of non-compliance to medical regimens.

Study Objectives The purpose of this study was to investigate whether perioperative use of low doses of opioids could reduce postoperative delirium . Conditions: Postoperative Delirium Intervention / Treatment: DRUG: Sufentanil Citrate, DRUG: Ropivacaine 0.75% Injectable Solution, PROCEDURE: Epidural catheter Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SCREENING Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients' age ≥65 years * Underwent elective radical gastrectomy Exclusion Criteria: * Mini-Mental Scale Test (MMSE) Exclusion criteria: illiteracy <18, primary school <21, junior school and above <25 * Preoperative clear systems and spiritual history of neurological disease or long-term use of sedatives or antidepressants * History of alcohol abuse or a history of drug dependence * Have brain surgery or trauma * Cannot with the completion of tests of Postoperative Cognitive Dysfunction * Refused to participate in the study

Study Objectives Indocyanine green NIR imaging is valuable for lymph node dissection in D3 radical surgery for rectal cancer. It can guide the intraoperative improvement of lymph node dissection based on the preservation of LCA and peripheral autonomic nerves of IMA. This not only reduces the occurrence of postoperative complications and promotes rapid postoperative recovery, but also provides a more precise and individualized comprehensive treatment plan for patients after surgery. In addition，this trial also demonstrated that ICG is safe and feasible for use in rectal cancer Conditions: Indocyanine Green Intervention / Treatment: OTHER: non-ICG, DRUG: ICG Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * The preoperative colonoscopic pathological diagnosis was clearly rectal cancer and no malignant tumor in other sites. * Good preoperative general condition, no serious cardiopulmonary, hepatic, renal or other major comorbidities before surgery * Radical rectal cancer surgery with preservation of LCA and peripheral autonomic nerves of IMA in patients * No contraindications to surgery * No history of ICG or iodide allergy Exclusion Criteria: *

Study Objectives Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 are administered to support T cell activation and proliferation in vivo. In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy. Conditions: Metastatic Melanoma Intervention / Treatment: DRUG: Cyclophosphamide, DRUG: Fludarabine, BIOLOGICAL: TIL infusion, DRUG: Interleukin-2, DRUG: Peginterferon alfa-2b Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Histologically confirmed unresectable stage III or stage IV metastatic melanoma Metastasis available for surgical resection (about 2 cm3) and residual measurable disease after resection ECOG performance status 0-1 Life expectancy ≥ 3 months No significant toxicity from prior treatments Adequate renal, hepatic and hematologic function Women of childbearing potential (WOCBP) and men in a sexual relationship with a WOCBP must be using an effective method of contraception during treatment and for at least 6 months after completion af treatment. Able to comprehend the information given and willing to sign informed consent * Exclusion Criteria: Other Malignancies, unless followed for ≥ 5 years with no sign of disease, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri. Cerebral metastasis. Patients with previously treated CNS metastases can participate if CNS metastases are surgically removed or treated with stereotactic radiosurgery and stable ≥ 28 days after treatment measured by MRI. Patients with asymptomatic, stable and untreated CNS metastasis can in be included according to investigators and sponsors decision. Patients with ocular melanoma Severe allergies, history of anaphylaxis or known allergies to the administered drugs. Serious medical or psychiatric comorbidity Creatinine clearance < 70 ml/min Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis Severe and active autoimmune disease Pregnant and nursing women Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate Concomitant treatment with other experimental drugs Patients with uncontrolled hypercalcemia Less than four weeks since prior systemic antineoplastic treatment at the time of treatment. *

Study Objectives This is a Phase II study. The purpose of this study is to find out what effects, good and/or bad enzalutamide has on the patient and the cancer. All patients who enter the study will be closely monitored for side-effects. If multiple patients develop significant side effects from enzalutamide, the study may be stopped early. Enzalutamide is an androgen-receptor inhibitor, which means that it blocks the activity of the hormone testosterone. In ovarian, fallopian tube, and primary peritoneal cancers that express the androgen receptor, blocking the androgen-receptor may possibly slow or stop tumor growth. Enzalutamide has been studied in women with breast cancer, but this is the first study using enzalutamide for the treatment of patients with ovarian, primary peritoneal, or fallopian tube cancer. Conditions: Advanced Epithelial Ovarian, Recurrent Epithelial Ovarian, Fallopian Tube, Primary Peritoneal Carcinoma Intervention / Treatment: DRUG: Enzalutamide 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: * Advanced or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Histologic documentation of the original primary tumor is required via the pathology report * AR expression ≥5% by IHC. In cases where multiple blocks are available staining will be performed on unstained slides from 3 separate blocks. If ≥ 5% AR tumor staining is seen on ≥ 1 slide the tumor will be considered to be AR+. * Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified * Measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. Each lesion must be ≥10mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20mm when measured by chest x-ray. Lymph nodes must be ≥ 15mm in short axis when measured by CT or MRI * Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease * Patients may have received, but are not required to have received, one or two additional cytotoxic regimens for management of recurrent or persistent disease * Patients who have received only one prior cytotoxic regimen (platinum-based regimen management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy * Patients are allowed to receive, but are not required to receive, non-cytotoxic therapy (such as bevacizumab) as part of their primary treatment regimen. * Patients are allowed to receive, but are not required to receive, non-cytotoxic therapy for management of recurrent or persistent disease * Must be ≥ 18 years of age * Karnofsky Performance Status (KPS) of ≥ 70% * Life expectancy of ≥ 12 weeks Women of child-bearing potential must have a negative pregnancy test within 14 days prior to commencement of study treatment * Women of child bearing potential must use an effective form of contraception during study and for at least 6 months after completion of study treatment * Recovery from effects of recent surgery, radiotherapy, or chemotherapy * At least 4 weeks out from their last dose of radiation therapy * At least 4 weeks post-op from any major surgical procedure * At least 3 weeks out from their last dose of chemotherapy and/or biologic/targeted therapy * No prior hormonal therapy for treatment of cancer within the past 21 days * Absence of any psychological, familial, sociological or geographic condition that would potentially hamper compliance with the study protocol * Prior use of or participation in a clinical trial evaluating and agent that either blocks androgen synthesis (e.g. abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the AR (e.g., bicalutamide, BMS-641988) (patients who are known to have only received placebo in these studies are eligible) * Laboratory Test Findings performed within 14 days prior to initiation of study drug showing: Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,000/mcL Platelets ≥ 100,000/mcL Hemoglobin ≥ 8 g/dL o Renal function: Creatinine ≤ 1.5 x ULN o Hepatic function: Bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN * Resolution of all acute toxic effects of prior therapy to NCI CTCAE (Version 4.0) Grade ≤ 1, with the exception of unresolved Grade 2 neuropathy and Grade 2 alopecia, which are allowed * Patients must be able to swallow tablets whole, without crushing Exclusion Criteria: * A history of another invasive malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma) with evidence of disease within the past 3 years * Use of a medication known to lower the seizure threshold within 28 days of first dose of study drug * Known brain metastasis * History of seizure * Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) despite medical treatment. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment. * Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic event within the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline * Refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition, drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study drug absorption * Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study

Study Objectives Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD) and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. This research project will investigate the use of particular pre-transplant conditioning regimen (chemotherapy, antibodies and total body irradiation) followed by a stem cell infusion from a "mismatched" family member donor. Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device. The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment, as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment. Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor. Conditions: Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML), Juvenile Myelomonocytic Leukemia(JMML), Hemoglobinuria, Paroxysmal Nocturnal (PNH), Lymphoma, Non-Hodgkin (NHL), Myelodysplastic Syndrome (MDS) Intervention / Treatment: DEVICE: Miltenyi Biotec CliniMACS, PROCEDURE: Stem Cell Transplantation, DRUG: TBI, systemic chemotherapy and antibodies as follows: Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Lacking a HLA-identical sibling or unrelated donor matched at 6 HLA loci formally requested within an approximate 90 day period from search initiation and who has a mismatched family member donor available * At least 2 and less than or equal to 21 years of age * Must have one of the following diagnosis: * Acute lymphoid leukemia (ALL) in second, third, or subsequent remission. * ALL in first remission but high risk for relapse. * Acute myeloid leukemia (AML) in relapse or remission. * Secondary AML / MDS * Chronic myeloid leukemia (CML) * Juvenile myelomonocytic leukemia (JMML). * Myelodysplastic syndrome (MDS). * Paroxysmal nocturnal hemoglobinuria (PNH) * Non-Hodgkin lymphoma in second or subsequent CR * Patients with a shortening fraction ≥ 25% * Patients with a creatinine clearance ≥ 40cc/min/1.73m\^2 * Patients with FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air * Patients with direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L * Patients with a Karnofsky or Lansky (age dependent) performance score of ≥ 70 * Mismatched family member donor is available, HIV negative and ≥ 18 years of age Exclusion Criteria: * Patients who have received a previous hematopoietic stem cell allograft * Patients with a known allergy to rabbit or murine products * Patients with isolated CNS, testicular or other isolated extramedullary site of relapse

Study Objectives This pilot study is an open-label interventional study, prospective, non-comparative, sequential (two stages), national, multicenter study. Patients starting therapy with sunitinib or pazopanib as standard first line treatment for advanced or metastatic renal cell carcinoma will enter the study in one of the two cohorts (115 patients will be treated by sunitinib and 99 patients will be treated by pazopanib). The purpose of this study is to examine the feasibility of sunitinib and pazopanib dose individualisation based on therapeutic drug monitoring (TDM) and to assess the benefit of this approach in terms of tolerance and efficacy compared with the current empirical method based only on tolerance observation. Conditions: Metastatic Renal Cell Cancer Intervention / Treatment: DRUG: Pazopanib, DRUG: Sunitinib Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: OTHER Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients starting therapy with sunitinib or pazopanib as standard first line treatment for advanced or metastatic renal cell carcinoma. * Measurable tumours as defined by RECIST criteria version 1.1. * Age ≥ 18 years old. * WHO Performance Status ≤ 2. * Life expectancy ≥ 6 months. * Adequate cardiac function (baseline Left Ventricular Ejection Fraction (LVEF) ≥ 50% determined by Multiple Gated Acquisition scan (MUGA) or echocardiography) and pulmonary function. * Renal function defined as creatinine clearance (Cockcroft and Gault formula) > 30 mL/min. * Adequate liver function defined as: total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN); Alanine AminoTansferase (ALAT) and Aspartate AminoTransferase (ASAT) ≤ 2.5 x ULN; Concomitant elevation in bilirubin and ASAT/ALAT above 1.0 x ULN is not allowed. * Patients 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. * Negative pregnancy test for women in childbearing potential. * Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study (before study entry and until 30 days after the last administration of study treatment). * Patients affiliated to a social health insurance. Exclusion Criteria: * Patients without any venous access for blood sampling. * Hypersensitivity to the active substance or to any of the excipients. * History or clinical evidence of central nervous system (CNS) metastases, except for individuals who have previously-treated CNS metastases. * Corrected QT interval (QTc) > 480msecs using Bazett's formula. * Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to: * Uncontrolled infection. * Cardiovascular conditions within the last 6 months such as 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 irregular heartbeat requiring medication. * Poorly controlled hypertension \[defined as systolic blood pressure of ≥140 mmHg or diastolic pressure of ≥90 mmHg). * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or deep venous thrombosis (DVT) within the past 6 months. Note: patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. * Evidence of active bleeding or bleeding diathesis. * Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme cytochrome P450 isoenzyme 3A4 (CYP3A4) within the last 14 days prior to inclusion and/or during the study. * Patients already treated with an anticancer treatment in the previous four weeks or patient requiring anticancer treatment during the study (chemotherapy, immunotherapy, hormonotherapy, radiotherapy or surgery). * Pregnant or breast-feeding women. * Positive diagnostic of HIV, B and C hepatitis. * Patients with serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures. * Patients who has forfeited his/her freedom by administrative or legal award or who is under guardianship.

Study Objectives This randomized phase II trial studies how well giving celecoxib with or without eflornithine works in preventing colorectal cancer in patients with familial adenomatous polyposis. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of celecoxib and eflornithine may keep cancer from forming in patients with familial adenomatous polyposis. Conditions: Colorectal Cancer, Familial Adenomatous Polyposis Intervention / Treatment: DRUG: Celecoxib, OTHER: Placebo, DRUG: eflornithine, OTHER: Laboratory biomarker analysis, OTHER: Questionnaire administration Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * REGISTRATION INCLUSION CRITERIA: * Diagnosis of FAP based on any of the following will be acceptable: * > 100 polyps or * > 10 polyps and age < 40 years, or > 25 polyps and age > 40 years and characteristic family history (autosomal dominant pattern) including: * > 100 polyps in a first degree family member or * > 25 polyps in two relatives in two generations, including a first degree family member or * Genetic diagnosis in a relative or * Genetic diagnosis by in vitro synthesized protein (IVSP) or similar assay * Willingness to abstain from use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, for the duration of the study; a cardio-protective dose of aspirin (>= 80 mg) may be permitted but must be reviewed/approved by principal investigator (PI) * If participant is female and of child bearing potential, she agrees to participate in this study by providing written informed consent, has been using adequate contraception (e.g. abstinence, condom, intrauterine device \[IUD\], birth control pill, diaphragm and spermicide gel combination) since her last menses and will use adequate contraception during the study, is not lactating, and agrees to undergo a serum pregnancy test at baseline, month 3 and month 6; sexually active males must agree to use an accepted and effective method of contraception * Colon polyp status: the participant has an endoscopically assessable colonic and/or rectal segment * Participant has no clinically significant hearing loss that is defined by the patient reporting that their hearing loss affects their everyday life and/or wears a hearing aide * Participants whose air conduction pure tone audiogram reveals a deficit that differs from the age specific norm by less than 30 dB when averaged across two contiguous test frequencies in either ear are eligible, as long as no self-reported hearing deficit or tinnitus is present * Willingness and ability to sign informed consent * RANDOMIZATION INCLUSION CRITERIA: * The individual has assessable colonic polyps remaining in the colon or rectum post baseline colonoscopy or flexible sigmoidoscopy * Potential participants must have the following colonic or rectal polyp burden at the conclusion of the baseline endoscopy: * Rectum: * Five or more polyps >= 2 mm diameter * Colon: * Five or more polyps >= 2 mm diameter including: * Three quantifiable polyps > 3 mm diameter, or two quantifiable polyps > 5 mm diameter * In the colon, quantifiable polyps are defined as being within a composite "cloverleaf" photograph that includes a tattoo, the appendix, or the ileocecal valve Exclusion Criteria: * REGISTRATION EXCLUSION CRITERIA: * Anticipated colectomy within eight months of randomization * History of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs or salicylates * Chronic use of NSAIDs, including aspirin or Celebrex, at any dose during the six months prior to study entry will require a three-month washout period prior to eligibility beginning with the time of the patient's last dose; participants must voluntarily agree to be off all NSAIDs for three months prior to study enrollment; a cardio-protective dose of aspirin (>= 80 mg) may be permitted but must be reviewed/approved by PI * The use of fluconazole, lithium or chronic use of adrenocorticosteroids * History in the past year of discrete gastric or duodenal ulcer of size > 5 mm, except that those with a history of Helicobacter pylori related peptic ulcer disease will become eligible for study upon successfully completing antibiotic treatment of Helicobacter pylori * History of invasive carcinoma in the past five years other than resected Duke's A/B1 colon cancer or resected non-melanomatous skin cancer * Partial or complete colectomy within 12 months prior to enrollment * Inability to return for follow-up tests * Significant medical or psychiatric problems, (including significant renal, hepatic or hematologic dysfunction) which would make the individual a poor protocol candidate * Use of any investigational agent within the last 3 months, or at the discretion of the medical monitor * History of pelvic radiation * RANDOMIZATION EXCLUSION CRITERIA: * Anticipated colectomy within eight months of randomization; the results of the initial endoscopies, including pathology reports and blood tests will be reviewed by the study endoscopist and surgeon prior to initiation of drug treatment to determine if the patient can remain on study * Discrete gastric or duodenal ulcer of size > 5 mm; patients with Helicobacter pylori related peptic ulcers of > 5 mm at the time of the baseline endoscopy will become eligible upon endoscopically documented successful treatment of Helicobacter pylori and of the ulcer(s). * Hemoglobin (Hgb) < 10.0 gm/dl * Platelet count < 100,000/ml * White blood cell (WBC) with differential < 3,000/ml * Serum glutamate pyruvate transaminase (SGPT) > 1.5 x upper limit of normal, serum glutamic oxaloacetic transaminase (SGOT) > 1.5 upper limit of normal * Alkaline phosphatase > 1.5 x upper limit of normal * Bilirubin > 2 x upper limit of normal * Creatinine > 1.5 x upper limit of normal * Has had a positive serum pregnancy test within 14 days prior to baseline randomization * Known or prior coagulopathy * Elevated C-reactive protein (CRP) (> 3.0 mg/L) * History of cardiovascular diseases or risk factors that might include one of the following: myocardial infarction, angina, coronary angioplasty, congestive heart failure, stroke, or coronary bypass surgery * Uncontrolled hypertension (> 135/> 85 mm Hg on three repeated measurements during the 6 weeks prior to enrollment on the study); this pertains to subjects with known diagnosis of hypertension; such subjects will have been invited to participate in the trial following successful treatment of their known hypertension; subjects with diagnosis of hypertension established at study entry will be considered cases of potential "white coat" hypertension; such subjects will be otherwise evaluated for protocol and randomized if they agree to be monitored for blood pressure (BP); if BP remains persistently elevated, subjects will be allowed to remain on-study for three months while undergoing antihypertensive therapy and monitoring; if, at the end of 3 months, subjects cannot demonstrate successful BP control as measured and documented locally, dosing will be suspended; such subjects will nevertheless be urged to complete 6-month off study evaluation, for intention to treat analysis * Family history of premature coronary disease (i.e. onset < 55 years of age) * Uncontrolled diabetes; subjects with preexisting diagnosis of diabetes will be eligible to participate in the trial if able to document acceptable management by their treating physician; subjects with diagnosis of diabetes established at study entry will be considered cases of new onset disease; such subjects will be otherwise evaluated for protocol and randomized if they agree to blood sugar monitoring; if glucose remains persistently elevated, subjects will be allowed to remain on-study for three months while undergoing therapy and monitoring; of, at the end of 3 months, subjects cannot demonstrate successful glucose control as measured and documented locally, dosing will be suspended; such subjects will nevertheless be urged to complete 6-month off study evaluation, for intention to treat analysis * Uncontrolled hypercholesteremia (low-density lipoprotein cholesterol \[LDL-C\] > 130); hypercholesteremia needs to be controlled following the updated National Cholesterol Education Program Adult Treatment Panel III Guidelines for at least 3 months prior to enrollment on the study; hypercholesteremia treatment should continue during the entire period of Celecoxib treatment on the protocol; this pertains to subjects with known diagnosis of hypercholesterolemia; such subjects will have been invited to participate in the trial following successful treatment of their elevated cholesterol; subjects with diagnosis of hypercholesterolemia established at study entry will be considered cases of new onset disease; such subjects will be otherwise evaluated for protocol and randomized if they agree to cholesterol treatment and monitoring; subjects will be allowed to remain on-study for three months while undergoing therapy and monitoring; if, at the end of 3 months, subjects cannot demonstrate successful cholesterol control as measured and documented locally, dosing will be suspended; such subjects will nevertheless be urged to complete 6-month off study evaluation, for intention to treat analysis * Metabolic syndrome diagnosis; the diagnosis of metabolic syndrome is made when three or more of these risk factors are present: * Waist circumference: Men > 102 cm (> 40 in.); women > 88 cm (> 35 in.) * Triglycerides > 150 mg/dl ( > 1.69 mmol/L) * High-density lipoprotein cholesterol (HDL-C): Men < 40 mg/dl (< 1.03 mmol/L), women < 50 mg/dl (< 1.29 mmol/L) * Blood pressure > 130/85 mm Hg * Fasting glucose > 110 mg/dl (> 6.1 mmol/L) * History of deep venous thrombosis, pulmonary embolism, systemic lupus erythematous, family history of protein S or C deficiencies, prior heparin-induced thrombocytopenia, Factor V Leiden deficiencies or high homocysteine levels * Any indications for acetylsalicylic acid (ASA)

Study Objectives This is an open-label, multicenter phase II study in patients with aggressive Non Hodgkin Lymphoma scheduled to receive moderately emetogenic polychemotherapy (according to modified Hesketh classification for antiemetic therapy). Conditions: Chemotherapy-Induced Nausea and Vomiting, Non Hodgkin's Lymphoma Intervention / Treatment: DRUG: Palonosetron Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female, >18 years of age; * Histologically or cytologically confirmed aggressive NHL (any stage in accordance with the REAL Classification); * Patients candidates to a initial chemotherapy treatment; * ECOG performance status of 0-1; * Scheduled to receive a single intravenous dose of at least one of the moderately emetogenic agents (according to the modified Hesketh classification) on Day 1; * Written informed consent; * Female of childbearing potential must be using reliable contraceptive measures; * Acceptable hepatic and renal functions; * Willing and able to complete the patient diary. Exclusion Criteria: * Highly emetogenic chemotherapy (containing cisplatin, mechlorethamine, streptozotocin, cyclophosphamide >1500 mg/sqm; carmustine; dacarbazine; hexamethylmelamine; procarbazine), or single-agent chemotherapy with drugs having low/minimal emetogenic potential according to the Hesketh classification); * Diagnosis of Hodgkin's Disease or Leukemia; * Candidates to High-Dose Chemotherapy or Bone Marrow/Peripheral Blood Stem Cells Transplantation; * Chemotherapy schedules considering the administration of emetogenic drugs in more than two consecutive days; * Have received any investigational drugs within 30 days before study entry; * Have received any drug with potential anti-emetic efficacy (with the exception of specific corticosteroids foreseen in the chemotherapy combination) within 24 hours of treatment initiation); * Prior treatment with Palonosetron; * Have a seizure disorder requiring anticonvulsant medication unless clinically stable and free of seizure activity; * Experienced or ongoing vomiting or nausea from any organic etiology, in the screening phase; * Clinical evidence of current or impending bowel obstruction, peritonitis, infection, uremia, severe mucositis; * Clinically relevant electrolyte abnormalities; * Have a known hypersensitivity to 5HT3 receptor antagonists; * Radiotherapy within 30 days before chemotherapy administration, or scheduled to receive radiotherapy within two weeks after chemotherapy; * Female patients who are pregnant or breast feeding; * Inability to understand or cooperate with the study procedures.

Study Objectives RATIONALE: Giving chemotherapy, such as cyclophosphamide and busulfan, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells from bone marrow or umbilical cord blood may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving methotrexate and cyclosporine after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Conditions: Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm Intervention / Treatment: DRUG: busulfan, DRUG: cyclophosphamide, BIOLOGICAL: Stem cell infusion, RADIATION: Total body irradiation 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: * Donors will be <55 years of age and in good health as approved by the National Marrow Donor Program (NMDP) donor and collection centers. Related donors will be < 70 years of age. * Recipients will be <55 years, will have satisfactory organ function (excluding bone marrow) and will have a Karnofsky activity assessment >90% and will have: * Creatinine <2.0 mg/dl. * Bilirubin, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2 x normal. * Pulmonary function test and Carbon Monoxide Diffusing Capacity (DLCO) > 50% of normal. * Multi Gated Acquisition Scan (MUGA) >45% injection fraction. * Recipients with unrelated donor matched at the HLA A, B, DRBI loci, or if < 35 years mismatched at a single HLA A or B, or DRBI locus. * Umbilical cord blood (5) used as an unrelated stem cell source will provide > 2.0 x 10\^7 cells/kg and will be matched at 4 - 6 of 6 HLA A, B, and DRBI loci. Cord blood grafts may include a single or pair of cord units depending on the cell dose. * Partially matched related donors will be at least haploidentical (matched at >3 of 6 HLA A, B, DRB1 loci). * Recipients will fall under one of the following disease categories * Chronic lymphocytic leukemia -- must have all three: * Rai Stage III/IV * Progression after previous Complete Response (CR) or Partial Response (PR) including purine antagonist (i.e. fludarabine). * Recent chemotherapy responsiveness * Advanced non-Hodgkin's lymphoma(NHL). * Low-grade NHL (Working Formulation A, B, C) following progression after initial therapy if asymptomatic at diagnosis (>CR2, >PR2; response duration < 1 year from last therapy) or if no CR was achieved (>PR1). At least one prior therapy of intermediate intensity (e.g. CHOP). * Mantle zone lymphoma after any progression following initial therapy (>CR1, > PR1). At least one prior therapy of intermediate intensity (e.g. CHOP). * Intermediate grade lymphoma (>PR2). Response duration <1 year from prior therapy. * High-grade Non-Hodgkin's Lymphoma (NHL) (IWF H, I, J) after initial therapy if >stage III at diagnosis; after any progression even if localized (stage I, II) at diagnosis with prior response duration < 1 year. * Recent chemotherapy responsiveness after treatment with > 3 intermediate intensity regimens. * Advanced Hodgkin's disease beyond PR2 (>CR3, >PR3). * Recent chemotherapy responsiveness * Multiple Myeloma (>CR2, >PR2) or after initial therapy if no prior PR. * Recent chemotherapy responsiveness * Recipients will sign informed consent approved by the Committee on the Use of Human Subjects at the University of Minnesota. Exclusion Criteria: * No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.

Study Objectives RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Iloprost may be effective in preventing lung cancer. PURPOSE: This randomized phase II trial is studying how well iloprost works in preventing lung cancer in patients who are at high risk for this disease. Conditions: Lung Cancer, Precancerous Condition Intervention / Treatment: DRUG: iloprost, OTHER: placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Current or former smoker with ≥ 20 pack-year history of smoking with no tobacco use within the past 6 months * Mild atypia or worse on sputum cytology, or * Bronchial biopsy with mild or worse dysplasia within the past 12 months * Age 18 and over * SWOG (Southwest Oncology Group)0-2 * Life expectancy at least 6 months * Granulocyte count > 1,500/mm\^3 * Platelet count > 100,000/mm\^3 * Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN) * Transaminases ≤ 2.5 times ULN * Bilirubin ≤ 2.0 mg/dL * Albumin ≥ 2.5 g/dL * Creatinine ≤ 1.5 mg/dL * Well-controlled atrial fibrillation OR rare (< 2 minutes) premature ventricular contractions allowed * Negative pregnancy test * Fertile patients must use effective contraception * Able and willing to undergo bronchoscopy Exclusion Criteria * Clinically apparent bleeding diathesis * Ventricular tachycardia * Multifocal premature ventricular contractions or supraventricular tachycardias with rapid ventricular response * Pneumonia or acute bronchitis within the past 2 weeks * Hypoxemia (< 90% saturation with supplemental oxygen) * Pregnant or nursing * Malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * Serious medical condition that would preclude bronchoscopy or study participation * Clinically active coronary artery disease * Myocardial infarction within the past 6 weeks * Chest pain * Congestive heart failure * Cardiac dysrhythmia that is potentially life-threatening Exclusion for PRIOR CONCURRENT THERAPY: * Biologic therapy (Not specified) * More than 5 years since prior chemotherapy * More than 6 weeks since prior inhaled steroids * More than 5 years since prior thoracic radiotherapy * Surgery (Not specified) * No prior prostacyclin

Study Objectives The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-486 (ONUREG®) in combination with venetoclax in relapsed and/or refractory Acute Myeloid Leukemia (AML) and newly diagnosed AML. Conditions: Leukemia, Myeloid, Acute Intervention / Treatment: DRUG: CC-486, DRUG: Venetoclax Location: United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Confirmation of the following for Acute Myeloid Leukemia (AML) * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. ECOG 3 is allowed if participants are 18 to 74 years old with comorbidities * Agree to serial bone marrow aspirate/biopsies Exclusion Criteria: * Suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype * Received prior hypomethylating agent (HMA) therapy for myelodysplastic syndromes/Chronic myelomonocytic leukemia then develop AML within 4 months of discontinuing the HMA therapy * Prior history of malignancy unless the participant has been free of the disease for ≥ 1 year prior to the start of study treatment Other protocol-defined inclusion/exclusion criteria apply

Study Objectives Surgery within the posterior fossa is associated with the highest incidence and greatest severity of acute postoperative pain that may persist beyond the immediate postoperative period. The utilization of local nerve blocks of the scalp in children may provide analgesia with stable hemodynamics while reducing the need for other anesthetics such as inhaled anesthetics and opioids. This could in turn result in less side effects, higher patient and family satisfaction, and better outcomes. The use of ultrasound-guided greater occipital nerve block (GONB) for perioperative pain management of posterior fossa surgery in pediatrics is not previously reported. Conditions: Posterior Fossa Tumor Intervention / Treatment: DRUG: ultrasound guided Greater occipital nerve block, DRUG: control group C Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * ASA physical status I or II, * Glasgow Coma Scale (GCS) 15, * children scheduled for craniotomy for posterior fossa tumors Exclusion Criteria: * Refusal of patients guardians * Patients with suspected or proved allergic to local anesthetics * Emergency surgery, * Children with GCS < 15 * Craniotomy incision beyond the coverage of the block will be excluded from the study.

Study Objectives This phase II trial studies how well nivolumab and ipilimumab work in treating patients with hormone-resistant prostate cancer that has spread to other places in the body and express androgen receptor-variant-7 (AR-V7). Tumor cells expressing AR-V7 has been shown to be resistant to hormone therapy and some chemotherapy in patients with prostate cancer. Biomarker-driven therapy, such as nivolumab and ipilimumab, may work by blocking key biomarkers or proteins that help tumor cells to escape the immune system surveillance and this may help the immune system to kill tumor cells that express AR-V7. Conditions: Prostate Cancer, Recurrent Prostate Carcinoma, Stage IV Prostate Adenocarcinoma Intervention / Treatment: BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab, DRUG: Enzalutamide 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: * Histologically or cytologically confirmed adenocarcinoma of the prostate * Metastatic disease as defined by two or more bone metastases confirmed by bone scintigraphy or radiographic soft tissue metastasis * Detectable circulating tumor cells (CTCs) with detectable AR-V7 splice-variant by reverse transcriptase (RT)-polymerase chain reaction (PCR) For second cohort (amendment 1): The most recent therapy must be enzalutamide and enzalutamide will be continued for study duration despite progressive disease. The minimum required dose of Enzalutamide at enrolment should be no less than 80 mg once daily. * Known castration-resistant disease, defined according to Prostate Cancer Working Group 2 (PCWG2) criteria as: * Castrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L) * Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a gonadotropin-releasing hormone (GnRH) agonist in combination with an anti-androgen, must first progress through antiandrogen withdrawal prior to being eligible; the minimum timeframe to document failure of anti-androgen withdrawal will be four weeks * Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart; serum PSA at screening >= 2 ng/mL OR * Documented bone lesions by the appearance of two or more new lesions by bone scintigraphy OR * Bidimensionally-measureable soft tissue metastatic lesion assessed by computed tomography (CT) or magnetic resonance imaging (MRI) * Karnofsky performance status (KPS): >= 70% within 14 days before start of study treatment (Eastern Cooperative Oncology Group \[ECOG\] =< 1) * Life expectancy: at least 6 months * White blood count (WBC) >= 2000/uL * Neutrophils >= 1500/uL * Platelets >= 100 x10\^3/uL * Hemoglobin > 9.0 g/dL * Serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN * Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL) * Men who are sexually active with women of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product * WOCBP is defined as any female who has experienced menarche and has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL * No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin) * The subject is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination * The subject has been fully informed about the study and has signed the informed consent form and, where appropriate, Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information * NOTE: HIPAA authorization may be included in the informed consent or obtained separately Exclusion Criteria: * Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period * Has received external radiotherapy within the last 4 weeks prior to start of study treatment * Previous therapy with antiandrogens within 4 weeks * Patients should be excluded if they have had prior systemic treatment with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways * Symptomatic metastatic disease with signs of rapid progression per investigator's clinical judgment * Concurrent use of other anticancer agents or treatments, with the following exceptions: * Ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, denosumab (Prolia) or bisphosphonate (eg, zoledronic acid) is allowed; ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed * Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment * Symptomatic nodal disease, i.e. scrotal, penile or leg edema (>= Common Terminology Criteria for Adverse Events \[CTCAE\] grade 3) * Patients are excluded if they have active brain metastases or leptomeningeal metastases; subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration * Patients should be excluded if they have an active, known or suspected autoimmune disease (e.g. inflammatory bowel disease, rheumatoid arthritis, autoimmune hepatitis, lupus, celiac disease); subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger * Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease * Permitted therapies include topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by contact allergen) is permitted * Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen * Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection * Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Allergies and adverse drug reaction * History of allergy to study drug components * History of severe hypersensitivity reaction to any monoclonal antibody * Other primary tumor (other than castration-resistant prostate cancer \[CRPC\]) including hematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer) * Has imminent or established spinal cord compression based on clinical findings and/or MRI * Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to: * Any uncontrolled infection * Cardiac failure NYHA (New York Heart Association) III or IV * Crohn's disease or ulcerative colitis * Bone marrow dysplasia * Known allergy to any of the compounds under investigation * Unmanageable fecal incontinence

Study Objectives This is a phase 2, multicenter, randomized, open-label study to estimate the efficacy of talimogene laherparepvec as a neoadjuvant treatment followed by surgery compared to surgery alone in subjects with completely resectable stage IIIB, IIIC, or IVM1a melanoma. Conditions: Completely Resectable Stage IIIB, IIIC, or IVM1a Melanoma Intervention / Treatment: DRUG: Talimogene Laherparepvec, PROCEDURE: Immediate surgical resection of melanoma lesion(s) Location: Spain, Brazil, Switzerland, United States, Greece, Australia, Russian Federation, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically confirmed diagnosis of stage IIIB, IIIC or IVM1a melanoma eligible for complete surgical resection. * Prior systemic, regional and radiation anticancer therapies for melanoma must have been completed at least 3 months prior to randomization. * Subject must have measurable disease and must be a candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm. * Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must have a serum lactate dehydrogenase (LDH) ≤ 1.0 X upper limit of normal and adequate hematologic, hepatic, renal, and coagulation organ function- Other criteria may apply Exclusion Criteria: * Subject must not have primary ocular or mucosal melanoma, or history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia). * Subject must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease. * Subject must not have evidence of clinically significant immunosuppression or active herpetic skin lesions or prior complications of herpes simplex type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic systemic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use. * Subject known to have acute or chronic active hepatitis B, hepatitis C, or human immunodeficiency virus infection will also be excluded. * Subject must not have been treated previously with talimogene laherparepvec or tumor vaccine. Other criteria may apply

Study Objectives The purpose of this study is to evaluate the safety, tolerability and efficacy of VB-111 in patients with Relapsed Glioblastoma Multiforme. Conditions: Glioblastoma Multiforme Intervention / Treatment: DRUG: VB-111, DRUG: Bevacizumab Location: United States, Israel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Subjects must have a histologically confirmed diagnosis of glioblastoma multiforme or gliosarcoma; * Measurable disease by RANO criteria; * Disease progression or recurrence following standard of care treatment with temozolomide and radiation; * An interval of at least 4 weeks between prior surgical resection and study enrollment; * An interval of at least 12 weeks between prior radiotherapy or at least 4 weeks from prior chemotherapy, and enrollment in this protocol; * Recovered to Grade 1 or less from the toxic effects of any earlier intervention; * Karnofsky performance status > 60% Exclusion Criteria: * Prior anti-angiogenic therapy including VEGF sequestering agents (ie bevacizumab, aflibercept, etc) or VEGFR inhibitors (cediranib, pazopanib, sunitinib, sorafenib, etc); * Prior stereotactic radiotherapy; * Active infection; * Evidence of CNS haemorrhage CTCAE grade 2 or above on baseline MRI; * Subjects who suffered from an acute cardiac event within the last 12 months; * Subjects with active vascular disease, either myocardial or peripheral; * Subjects with proliferative and/or vascular retinopathy; * Subjects with known active second malignancy;