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Study Objectives The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations. Conditions: Melanoma Intervention / Treatment: DRUG: LGX818, DRUG: MEK162, DRUG: LEE011, DRUG: BGJ398, DRUG: BKM120, DRUG: INC280 Location: Germany, Canada, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

INCLUSION CRITERIA: * Age ≥ 18 years * Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer \[AJCC\]) * Documented evidence of BRAF V600 mutation. * Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated. * Evidence of measurable disease, as determined by RECIST v1.1. INCLUSION CRITERIA for triple combinations: Progressive disease following prior treatment with LGX818/MEK162 combination. PRINCIPAL EXCLUSION CRITERIA Symptomatic or untreated leptomeningeal disease. * Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for four weeks are allowed to enroll. Brain metastases must be stable at least 4 weeks with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs. * Patients who have developed brain metastases during Part I of the study may continue to Part II upon discussion with Novartis Medical Monitor. The brain metastasis must be either asymptomatic or treated and stable for at least 4 weeks and on a stable or tapering dose of steroids for at least 2 weeks. Patients with brain metastasis are not eligible for the combination with LEE011. * Known acute or chronic pancreatitis. * History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); * Clinically significant cardiac disease including any of the following: * CHF requiring treatment (NYH grade ≥ 2), * LVEF < 50% as determined by MUGA scan or ECHO * History or presence of clinically significant ventricular arrhythmias or atrial fibrillation * Clinically significant resting bradycardia * Unstable angina pectoris ≤ 3 months prior to starting study drug * Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug, * QTcF > 480 msec. Patients with any of the following laboratory values at Screening/baseline: * Absolute neutrophil count (ANC) <1,500/mm3 \[1.5 x 109/L\] * Platelets < 100,000/mm3 \[100 x 109/L\] * Hemoglobin < 9.0 g/dL * Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% LLN (lower limit of normal) * Serum total bilirubin >1.5 x ULN * AST/SGOT or ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present Additional exclusion criteria for the triple combinations: LGX818/MEK162/BKM120: * Patients with fasting glucose > 120 mg/dL or 6.7 mmol/L, and HbA1c > 8 %. * Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist: * Patient has a score ≥ 12 on the PHQ-9 questionnaire * Patient has ≥ CTCAE grade 3 anxiety LGX818/MEK162/BGJ398: * History and/or current evidence of significant ectopic mineralization/ calcification with the exception of calcified lymph nodes and asymptomatic vascular calcification. * Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivits etc., confirmed by ophthalmologic examination LGX818/MEK162/LEE011: * Patients with uncontrolled hypertension (please refer to WHO-ISHguidelines) are excluded from study. * QTcF >450 ms for males and >470 ms for females Congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3 and magnesium levels below the clinically relevant lower limits at study entry * Current evidence of brain metastasis or brain metastasis detected by mandatory CT/MRI at screening * PT/INR or aPTT > 1.5xULN Other protocol-defined inclusion/exclusion criteria may apply.

Study Objectives This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane. Conditions: HER2/Neu Over-expressing Locally Advanced Breast Cancer, Metastatic Breast Cancer Intervention / Treatment: DRUG: everolimus, DRUG: Placebo, DRUG: vinorelbine, DRUG: trastuzumab Location: Hungary, Turkey, United States, Greece, France, Poland, Israel, Thailand, Italy, United Kingdom, Singapore, Spain, Belgium, China, Mexico, Germany, Czech Republic, Japan, Australia, Slovakia, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent. * HER2+ status defined as IHC 3+ staining or in situ hybridization positive * Patients with resistance to trastuzumab * Prior taxane therapy * Patients with an ECOG performance status of 0 - 2 * Patients with measurable disease as per RECIST criteria * Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study; * Patients must meet laboratory criteria defined in the study within 21 days prior to randomization Exclusion Criteria: * Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer * More than three prior chemotherapy lines for advanced disease. * Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus * Peripheral neuropathy ≥ grade 2 at randomization * Active cardiac disease * History of cardiac dysfunction * Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer * Known hypersensitivity to any study medication * Breastfeeding or pregnant

Study Objectives This is a non-comparative, prospective, non-randomized single centre phase II clinical trial of Rituximab and alpha interferon immunotherapy following autologous stem cell transplant in patients with relapsed follicular lymphoma conducted at Toronto Sunnybrook Regional Cancer Centre/Sunnybrook and Women's Health Sciences Centre. Conditions: Follicular Lymphoma Intervention / Treatment: DRUG: Rituximab, DRUG: Alpha Interferon Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with 1-2 relapses of WHO Classification follicle centre NHL grade 1-2/3. Patients must have achieved at least a PR to previous treatment. * Central pathology review before registration * Ann Arbor stage III or IV * Measurable disease: defined as clinically or radiologically documented disease with at least one site bidimensionally measurable using clinical exam, CT or MRI performed in the 3 weeks prior to study enrollment. * ECOG performance status of <2. * Patients may have received not more than 1 prior course (4 infusions) of rituximab. Timing of rituximab must exceed 12 months prior to registration. Patients must have demonstrated at least a PR to rituximab if previously administered. * Patient consent according to institutional and university human experimentation committee requirements * Adequate Renal, hepatic and hematopoietic function test unless the abnormal values are thought to be due to involvement with lymphoma as defined by: Hb> 85 ANC >1000/mm3 Platelets >100,000/mm3 Serum/Total Bilirubin >=2 SI units AST/ALT <2x Upper Limit of Normal Exclusion Criteria: * Positive serology for HIV * Uncontrolled Infection * Pregnancy * CNS Metastases * History of Psychiatric Disorder * Other Malignancy (except nonmelanoma skin cancer) * Serious non-malignant disease (e.g., congestive heart failure, or active uncontrolled bacterial, viral, or fungal infections), or other conditions, which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives. * Major surgery, other than diagnostic surgery, within four weeks. * Presence of anti-murine antibody (HAMA) reactivity. These laboratory results must be available prior to receiving treatment for those patients * who have received prior murine proteins or patients who have allergies to murine proteins. * New York Heart Association Class III or IV heart disease (see Appendix H, Clinical Evaluation of Functional Capacity of Patients with Heart Disease in Relation to Ordinary Physical Activity) or myocardial infarction within the past six months. * Treatment with an investigational drug within 30 days or five half-lives (of the study drug with the longest half-life) prior to entry into the study, which ever is longer. * Previous chemotherapy, immunotherapy, radiotherapy, or investigational therapy for the treatment of other malignancy except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix within the last 5 years. * History of allergic reactions to compounds chemically related to Rituximab. * Refusal to practice contraception if of reproductive potential.

Study Objectives This phase Ib study will investigate dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of afatinib and ruxolitinib combination therapy, based on the preclinical data that inhibition of IL-6R/JAK1 signal transmission pathway will increase sensitivity to afatinib. Conditions: NSCLC Intervention / Treatment: DRUG: Afatinib plus Ruxolitinib combination therapy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Stage 4 NSCLC patients * disease progression after platinum doublet (all), EGFR TKI (if EGFR mutant), and crizotinib (if ALK positive) * Men and women aged 20 years or older * Recovery from previous drug-related toxicity: CTCAE 4.03 ≤ Grade 1 * ECOG 0 or 1 * able to orally take and retain drug * have a measurable or unmeasurable lesion under RECIST 1.1 Criteria * have proper hematological, renal, and hepatic functions * intention to use an acceptable contraception * able to read and understand the informed consent form Exclusion Criteria: * previous chemotherapy, radiation therapy, immunotherapy, or other anticancer therapy within 14 days * Clinically significant gastrointestinal disorder or malabsorption syndrome * Acute digestive disorder * major organ failure * Significant cardiac disorders * major operation of a main organ in 4 weeks * Untreated symptomatic brain metastasis * pregnant or nursing * previously diagnosed Interstitial lung disease(ILD) * previously treated with irreversible pan-HER inhibitor including Afatinib or Ruxolitinib * previously experienced hypersensitivity to an ingredient of the study drug * must receive CYP3A4 inducer or inhibitor persistently during the study period. * HIV positive or active hepatitis * threatening patient's safety is predicted

Study Objectives Primary Objectives: To investigate the efficacy of HBM9161 in patients with attack of MG in China Conditions: Myasthenia Gravis Intervention / Treatment: DRUG: HBM9161 Injection (680mg and 340 mg), DRUG: Placebos, DRUG: HBM9161 Injection (340 mg) Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Signed Informed Consent Form. * Male or female ≥ 18 years of age. * A female participant is eligible to participate if she is of: 1. Non-childbearing potential (physically infertile, including women who have been menopausal for 2 years or more); 2. Childbearing potential, negative serum pregnancy test results at screening visits, and agree to consistently use acceptable and effective contraceptive methods until 14 days after the final visit. * A male participant must take effective contraception during this clinical trial or their heterosexual partner must take effective contraception. * Meets MGFA myasthenia gravis clinical classification IIa-IVa (includes types IIa, IIb, IIIa, IIIb, and IVa) at the screening visit and at the baseline visit. * Screening and baseline MG-ADL score ≥ 6, and < 50% of them is from ocular muscle. * Stable background MG treatments at randomization. * Positive serologic test for AChR-Ab or MUSK-Ab at the screening visit and at least 1 of the following: 1. History of abnormal neuromuscular transmission test demonstrated by sign-fiber-electromyography or repetitive nerve stimulation OR 2. History of positive edrophonium chloride test OR 3. Participant has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician. Exclusion Criteria: * Use of rituximab, belimumab, eculizumab or any monoclonal antibody/Fc-fusion biologic for immunomodulation within 6 months prior to screening. * Immunoglobulins given by SC, IV(IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before screening. * Thymectomy performed < 12 months prior to screening. * Total IgG level <6g/L (at screening). * Participant has any laboratory abnormality (at screening) that, in the opinion of the investigator, is clinically significant, has not resolved at baseline, and could jeopardize or would compromise the participant's ability to participate in this study. * Have known autoimmune disease other than MG that would interfere with the course and conduct of the study (such as uncontrolled thyroid disease). * Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to screening. * History of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Participants must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies and a negative TB test at screening.

Study Objectives The purpose of this study is to evaluate the safety and effectiveness of epoetin alfa versus placebo in the treatment of persistent anemia caused by advanced cancer and aggressive cisplatin chemotherapy. Epoetin alfa is a genetically engineered protein that stimulates red blood cell production. Conditions: Anemia, Neoplasms Intervention / Treatment: DRUG: epoetin alfa Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients with cancer (except for rapid onset of severe leukemia and malignancies of the bone marrow and spleen) and having anemia resulting from cisplatin-containing chemotherapy * receiving cyclic chemotherapy for <=5 consecutive days every 3 or 4 weeks (for 3 cycles of chemotherapy) * Performance score of 0, 1, 2, or 3 (grades assessing patients' ability to perform daily activities) * having a life expectancy of at least 3 months * having a hemoglobin level <= 10.5 grams/deciliter, and signs and symptoms of physical stability for 1 month before the study (based on physical examination including vital signs, weight, and electrocardiogram) * with an ability to administer self-injections Exclusion Criteria: * Patients with a history of any blood disease * having signs and symptoms of significant disease/dysfunction not caused by the underlying cancer * receiving radiation therapy or surgery to decrease the number of cancer cells within 30 days before the start of the study * having a sudden and severe onset of illness within 7 days before the start of the study * having cancer that has spread to the brain, a history of seizures, uncontrolled high blood pressure, or an iron, folate, or vitamin B12 deficiency

Study Objectives This research protocol will evaluate the feasibility of administering neoadjuvant gemcitabine and nab-paclitaxel with hypofractionated, image guided, intensity modulated radiotherapy (HIGRT) in resectable and borderline resectable pancreatic cancer Conditions: Resectable Pancreatic Cancers Intervention / Treatment: DRUG: Gemcitabine/nab-Paclitaxel, RADIATION: Radiation therapy, OTHER: Sugical resection, DRUG: Adjuvant chemotheapy 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: * Patient has signed informed consent and is willing to comply with the protocol * Histologically or cytologically proven adenocarcinoma of the pancreas (within the last 90 days) * Either resectable or borderline resectable as determined on staging imaging (as defined by National Comprehensive Cancer Network \[NCCN\]) * Patient is 18 years or older * Karnofsky performance status 70 or greater * The ANC count ≥ 1500, the platelet count ≥ 100,000 and hemoglobin ≥ 9g/dL * Laboratory values meet the following constraints: Bilirubin less than or equal to 2 mg/dL; AST and ALT less than or equal to 3 x ULN (stenting to improve biliary obstruction is permitted) * No evidence of metastatic disease based on imaging of the chest, abdomen and pelvis. Exclusion Criteria: * Metastatic disease on pretreatment imaging * Prior systemic therapy * Prior abdominal radiation. Any prior radiation must be approved by the Radiation Oncology PI * Previous treatment for pancreatic cancer * Patients with any serious/poorly controlled medical or psychological conditions that would be exacerbated by treatment, would complicate protocol compliance * Pregnant or lactating. Adequate birth control must be used if of child bearing potential per institutional policy. Negative pregnancy test in female patients of child-bearing potential per institutional policy. Post-menopausal women must have had amenorrhea for at least 18 months to be considered non-child bearing * Clinically significant peripheral vascular disease * Presence of active or chronic infection * Clinically significant atherosclerotic cardiovascular disease including patients with New York Heart Class II/III/IV CHF, ventricular arrhythmias requiring medication, myocardial infarction, cerebrovascular accident, transient ischemic attack, coronary artery bypass grafting, angioplasty, cardiac or other vascular stenting within the past 6 months * History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within six months prior to treatment start * History of collagen vascular disease or inflammatory bowel disease (Crohn's or ulcerative colitis) * Current grade 2 or higher peripheral neuropathy * Anticoagulation with warfarin * History of arterial thromboembolic events or symptomatic pulmonary embolism within the past 6 months * Active bleeding diathesis or history of major bleeding, CNS bleeding, or significant hemoptysis within the past 6 months

Study Objectives This is a clincial validation study of a dried blood spot (DBS) method for the analysis of immunosuppressive and antifungal agents currently subject of therapeutic drug monitoring (TDM) in a pediatric population. The primary goal is to clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy goals include feasibility of the finger prick DBS method in the target population, to design an inventory of costs that will be incurred in future health-economic analyses and to construct a population PK model based on the available data collected for the primariy goal. Conditions: Hematologic Diseases, Oncology Problem, Kidney Diseases, Transplantation Infection Intervention / Treatment: PROCEDURE: blood drawing Location: Netherlands Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients aged between 2 and 18 years * Admitted to the Radboudumc pediatric ward * Having a venous catheter * Treated with at least 1 of the 9 drugs of interest * The drug concentration being at steady state * Signed informed consent Exclusion Criteria: * Parents and/or patients are not able to understand the Dutch language

Study Objectives A prospective pilot trial was proposed to patients with DLBCL, with IH or high adjusted IPI, up to the age of 60 y.o. This program consisted of 2 courses of high-dose R-CHOP-like regimen, followed by a course of high-dose methotrexate with cytarabin. For patients who achieved at least a PR, ASCT started with a BEAM regimen. Conditions: B-Cell Lymphoma Intervention / Treatment: DRUG: Rituximab Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age 18 to 60 y.o * Aggressive Large B-Cell Lymphoma (CD20+) * Ann Arbor stage III, IV * IH or high adjusted IPI * signed inform consent Exclusion Criteria: * Age < 18 ou > 60 y.o * other type of lymphoma * serology VIH + * other neoplasms apart from basal cell carcinoma or situ carcinoma

Study Objectives To evaluate whether a combination regimen of pentoxifylline, ursodeoxycholic acid and enoxaparin provides a protective effect on the liver parenchyma after high dose rate (HDR) brachytherapy. Conditions: Colorectal Cancer, Liver Metastases, Irradiation Damage, Radiation Induced Liver Disease Intervention / Treatment: DRUG: Pentoxifylline, DRUG: Ursodeoxycholic Acid, DRUG: Enoxaparin Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age 18 to 80 * If female, postmenopausal or surgically sterilized * Liver metastases from colorectal carcinoma scheduled for a CT/MRI-guided single-fraction interstitial HDR brachytherapy * Non-cirrhotic liver * Life expectancy longer than 6 months * willing and able to undergo all study procedures * Having voluntarily provided written and fully informed consent Exclusion Criteria: * Women who are pregnant, lactating or who are of childbearing potential * Liver cirrhosis * Hepatitis B * Hepatitis C * Patients being clinically unstable * Uncooperative, in the investigator's opinion * Having been previously enrolled in this study * Participating in another therapy-modulating clinical trial * Contraindication for MRI * Contraindication or hypersensitivity to one or more components of Gd-EOB-DTPA, Enoxaparin, Ursodeoxycholic acid and/or Pentoxifylline * Any prior irradiation therapy of the liver * Close affiliation with the investigational site; e.g. a close relative of the investigator * Severe coronary artery disease * Autoimmune diseases * Acute bacterial endocarditis * Active major bleedings and high rish of uncontrolled haemorrhage * Patients with severe or moderate renal impairment (GFR below 60 mL/min/1.73 m2 according to the MDRD or Cockroft-Gault formula, calculated from a creatinine value obtained within 1 week before each planned Primovist-enhanced MR examination)

Study Objectives Aim: to observe the graft versus tumor effect of Pegylated Interferonα-2b in patients with hematological malignancies relapsed after allogeneic hematopoietic stem cell transplantation (alloHSCT) Patients: patients relapsed after alloHSCT, men and women aged 14-60 years, without vital organ dysfunction or ongoing graft-verus-host disease (GVHD). Number of subjects: 50, Single center, one group, prospective. Drug: pegylated interferon alpha-2b (Peg Intron®; Schering-Plough) 1\~1.5ug/kg qw, until occurrence of grade II or higher grade of acute GVHD, or no response to treatment after 8 doses of treatments. Conditions: Hematological Neoplasms, Recurrence Intervention / Treatment: DRUG: Peg interferon alfa-2b Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age 14-60 years, male or female * Allo-HSCT recipients with malignant hematological diseases * Disease relapse after allo-HSCT, including hematological relapse, molecular relapse * Able to provide written informed consent and to comply with all study procedures Exclusion Criteria: * Pregnant or nursing woman * Cardiac ejection factor < normal lower limit * Active acute or chronic GVHD with immunosuppressant treatment * Known hypersensitivity or allergy to interferon * Patient might develop serious complications according to investigator's experiences * Patient is undergoing other experimental medication

Study Objectives This study evaluated the efficacy and safety of Everolimus in treating patients with Subependymal Giant Cell Astrocytomas associated with Tuberous Sclerosis Complex. Conditions: Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma Intervention / Treatment: DRUG: Everolimus, DRUG: Placebo Location: Germany, Canada, Italy, Netherlands, United Kingdom, United States, Belgium, Australia, Russian Federation, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * All Ages * Definite diagnosis of Tuberous Sclerosis according to the modified Gomez criteria * At least one Subependymal Giant Cell Astrocytoma of at least 1 cm in diameter * Evidence of SEGA worsening as compared to prior MRI scans * Females of child bearing potential must use birth control * Written informed consent Exclusion Criteria: * SEGA related surgery is likely to be required in the opinion of the investigator * Recent heart attack, cardiac related chest pain or stroke * Severely impaired lung function * Severe liver dysfunction * Severe kidney dysfunction * Pregnancy or breast feeding * Current infection * History of organ transplant * Surgery within two months prior to study enrollment * Prior therapy with a medication in the same class as Everolimus * Uncontrolled high cholesterol * Uncontrolled diabetes * HIV * Patients with metal implants thus prohibiting MRI evaluations Other protocol-defined inclusion/exclusion criteria may apply

Study Objectives The purpose of this study is to determine in a randomized, placebo-controlled, phase II trial if the combination of sulindac and erlotinib causes a significant regression of duodenal and colorectal adenomas in familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) patients. Conditions: Adenomatous Polyposis Coli Intervention / Treatment: DRUG: Erlotinib, DRUG: Sulindac, DRUG: Placebo A, DRUG: Placebo B Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Patients who are 18 years or older with a clinical or genetic diagnosis of FAP or attenuated FAP. * Presence of duodenal polyps with a sum of diameters ≥ 5mm. * Minimum of two weeks since any major surgery * WHO performance status ≤1 * Adequate bone marrow function as show by: normal leukocyte count, platelet count ≥ 120 x 109/L, Hgb > 12 g/dL * Adequate liver function as shown by: normal serum bilirubin(≤ 1.5 Upper Limit Normal {ULN}) and serum transaminases (≤ 2.0 ULN) * Patient must discontinue taking any Nonsteroidal anti-inflammatory drugs (NSAIDS) within one month of treatment initiation. * Patients must be able to provide written informed consent. Exclusion Criteria: * Prior treatment with any investigational drug within the preceding 4 weeks. * Malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skins. * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study as determined by the Principal Investigator such as: 1. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia 2. Severely impaired lung function 3. Any active (acute or chronic) or uncontrolled infection/ disorders. 4. Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy 5. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis * Screening clinical laboratory values that indicate any of the following: 1. anemia 2. thrombocytopenia 3. leucopenia 4. elevations of transaminases greater than 2X ULN 5. elevation of bilirubin > 1.5 X ULN 6. alkaline phosphatase elevation > 1.5 X ULN 7. increased creatinine, urinary protein, or urinary casts outside the clinically normal range. * Gastrointestinal bleeding (symptoms including dyspnea, fatigue, angina, weakness, malaise, melena, hematochezia, hematemesis, anemia or abdominal pain will require clinical assessment to rule out gastrointestinal bleeding). * Patient who is currently taking any anti-coagulation medication. * Women who are pregnant or breast feeding. * Patients with a known hypersensitivity to sulindac or erlotinib or to their excipients

Study Objectives This study is to evaluate the safety and tolerability profile of Recombinant Nonavalent (Types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia Coli) in healthy women ages 18-45 Conditions: Human Papillomavirus Infection Intervention / Treatment: BIOLOGICAL: Recombinant Nonavalent (Types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia Coli), BIOLOGICAL: Recombinant nonavalent Human Papillomavirus (Types 6,11,16,18,31,33,45,52,58) Vaccine Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: Stage 1: * Female subjects 27-45 years of age (inclusive of 27 and 45 years of age); * Subjects decided to be healthy by the principal investigator in accordance with such trial subjects' medical history and physical examination results; * Subjects who understand and agree to comply with the study procedures and provide written informed consent; * Subjects who are able to comply with protocol-specified requirements; * Subjects with negative urine pregnancy test result at screening; * Subjects with no childbearing potential (e.g. females who have undergone bilateral tubal ligation, hysterectomy, bilateral oophorectomy, etc.), or subjects with childbearing potential who have agreed to abstain from any sexual activity that could result in pregnancy or practice adequate contraception for at least 28 days prior to the first dose and throughout the study; * Subjects with axillary temperature≤37.0℃. Stage 2: * Female subjects 18-26 years of age (inclusive of 18 and 26 years of age); * Subjects decided to be healthy by the principal investigator in accordance with such trial subjects' medical history and physical examination results; * Subjects who understand and agree to comply with the study procedures and provide written informed consent; * Subjects who are able to comply with protocol-specified requirements; * Subjects with negative urine pregnancy test result at screening; * Subjects with no childbearing potential (e.g. females who have undergone bilateral tubal ligation, hysterectomy, bilateral oophorectomy, etc), or subjects with childbearing potential who have agreed to abstain from any sexual activity that could result in pregnancy or practice adequate contraception for at least 28 days prior to the first dose and throughout the study; * Subjects with axillary temperature≤37.0℃. Exclusion Criteria: The same exclusion criteria apply to both stage 1 and stage 2 * Women who are pregnant or breastfeeding, or planning for pregnancy in the following 7 months; * Women who have received other HPV vaccine(s) prior to dose 1 of the interventions; * Women who have received an investigational or unregistered drug or vaccine within 28 days prior to the first dose of the interventions, or plan to receive an investigational or unregistered drug or vaccine during the study; * Women who have known allergy history or who are allergic to any component of the interventions, such as penicillin and amikacin; * Women with a history of severe adverse reactions to previous vaccinations, such as allergies, urticaria, dyspnea, angioneurotic edema, or abdominal pain; * Women who have an autoimmune disease or immunodeficiency, are HIV positive, or have primary diseases in vital organs; * Women who have asthma that is unstable and requires urgent care, hospitalization and the use of oral or intravenous corticosteroids during the past two years; * Women who have diabetes mellitus (type I or II), with the exception of gestational diabetes; * Women with a history of thyroidectomy or thyroid diseases that required medical care within the past 12 months.; * Women with serious angioedema episodes within the past 3 years or requiring medical care over the past 2 years; * Women who have hypertension over 145/95 mm Hg at enrolment despite being treated by medication; * Women with coagulation disorders as diagnosed by a doctor (e.g. coagulation factor deficiency, coagulopathy, or platelet disorder) or coagulation difficulty; * Women with active malignancy, or treated malignancy for which there is no reasonable assurance of sustained cure, or malignancy that is likely to recur during the study; * Women with a history of epilepsy other than epilepsy with febrile seizures under two years of age, epilepsy secondary to alcohol use 3 years prior to alcohol withdrawal, or a singular epileptic seizure not requiring treatment within the past 3 years; * Women with the condition of asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen; * Women with a history of systematic chemotherapy in the past 5 years, a history of immunosuppressive therapy and cytotoxic therapy, and treatment with inhaled corticosteroids within the past 6 months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis), and women who received blood products in the 3 months prior to vaccination with the interventions; * Women who received a live attenuated vaccine during the 28 days prior to vaccination with the interventions; Women who received a subunit or inactivated vaccine, such as pneumococcal vaccine, or underwent antianaphylactic treatment during the 14 days prior to vaccination with the interventions; * Women who received a subunit or inactivated vaccine, such as pneumococcal vaccine, or underwent antianaphylactic treatment during the 14 days prior to vaccination with the interventions; * Women who are currently on an anti-TB prophylaxis or therapy; * Women who had fever (with axillary temperature≥38.0℃) during the 3 days prior to vaccination with the interventions or onset of any acute illness that required the use of antibiotics and antiviral treatment within the past 5 days; * Women with psychiatric conditions that preclude compliance with the protocol, or women with past or present psychoses, past or present bipolar disorder that has not been well controlled over the past 2 years, or women who are on medication for psychoses, or women who had suicidal thoughts/tendency in the past 5 years prior to enrolment; * Women with any medical, psychological or social conditions, or for occupational reasons or otherwise as judged by the principal investigator, that preclude participation in the study, or compromise a subject's ability to give informed consent.

Study Objectives This study aims to evaluate the Impact of a topical Lotion, CG428, on permanent chemotherapy induced hair and scalp disorders in Cancer survivors. This is a double-blind, single center, randomized, controlled trial in breast cancer survivors. Hair condition and parameters of 61 breast cancer survivors who were previously included in DERMA study (a prospective cohort study to assess appearance changes due to breast cancer treatment completed in July, 13th,2013) will be assessed. 1. Patients whose hair parameters are below the baseline as measured before the start of the chemotherapy or 2. who complain from incomplete hair regrowth will be eligible to participate in the randomized controlled trial. Patients who agree to participant in the study will be randomly assigned to two parallel arms (Arm 1: CG428/ Arm 2: Placebo). Patients will self-administer the study product or placebo twice per day (morning, evening) for 6 months, for the efficacy assessment. Primary endpoint was recovery of hair thickness 6 months after intervention as assessed using Folliscope 4.0. Secondary endpoints included hair density at 6 months after intervention, distress due to chemotherapy induced alopecia, scalp skin parameters (water and sebum). Patient-reported hair quality improvement, body image and quality of life, and time to first visible improvement based on global photographs of hair and nails. Conditions: Alopecia Intervention / Treatment: OTHER: CG428, OTHER: Placebo Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * hair parameters obtained before the start of chemotherapy * hair parameters obtained 6 months after the completion of chemotherapy * whose hair parameters are below the baseline, as measured before the start of chemotherapy during DERMA study, or * who complain from incomplete hair regrowth at the time of enrollment (on average 24 months after chemotherapy completion) * Able to keep their hair style * Able to use the study treatment in compliance with the protocol. * Physical (ECOG≤1) and psychological ability to participate Exclusion Criteria: * Concomitant use of other anti-hair-loss treatment or hair growth treatment. * Patients with recent hair transplants or who plan to have transplants. * Known allergy or hypersensitivity to some components of CG428 (including allium cepa (onion), citrus, caffeine, the obromine) * Pre-existing alopecia or significant scalp disease, which may alter study treatment administration or absorption.

Study Objectives The purpose of this study is to test whether calcium and/or vitamin D supplementation favorably affects a set of biomarkers of risk for colon cancer in persons who are at higher than average risk for colon cancer (ie, have already undergone the removal of adenomatous polyps, which are known to be precursors to developing colon cancer). Conditions: Colorectal Adenomatous Polyps Intervention / Treatment: DIETARY_SUPPLEMENT: Calcium and vitamin D3 combined, DRUG: Placebo, DIETARY_SUPPLEMENT: Calcium, DIETARY_SUPPLEMENT: Vitamin D3 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: FACTORIAL Masking: QUADRUPLE

Inclusion Criteria: * age 30-74 * adenomatous colon polyp within past 3 years * general good health with life expectancy of at least 2 years * available for 8 months and able to come for clinic visits Exclusion Criteria: * cancer within 5 years * active major disease * renal impairment * history of kidney stones * significant dietary change or weight loss within past 6 months * unable to forego usual calcium or vitamin D use during study

Study Objectives EMI-137 in laparoscopic colonic resections is a single-centre stage IIa developmental study. Ten adult participants with a diagnosis of colon adenocarcinoma undergoing laparoscopic colonic will be recruited to the trial. Participants will receive a single intravenous dose of the IMP - EMI-137 1 to 3 hours before surgery. The ability of EMI-137 to produce visible intra-operative fluorescence of primary colon cancer and lymph node metastases will be explored and evaluated. Conditions: Colonic Cancer, Metastasis to Lymph Node Intervention / Treatment: DRUG: EMI-137 Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age ≥ 18 years. * Patients with a diagnosis of colonic cancer (the disease can be of any radiological TMN stage and be located anywhere from the caecum up to but not including the rectosigmoid junction) * Patients with or without distant visceral or lymphatic metastatic disease. * Patients with synchronous colon cancers or polyps can participate. * American Society of Anaesthesiologists (ASA) classification ≤3. * Normal hepatic and renal function (eGFR ≥60 mls/min/1.73m2) and bilirubin within institutional limits and/or ALT ≤2.5x upper limit of institutional normal value) on serum laboratory blood tests performed ≤30 days prior to EMI-137 administration. * Female participants who are surgically sterile (documented bilateral oophorectomy and/or hysterectomy), post-menopausal (cessation of menses for more than 1 year), or pre-menopausal with two negative urine pregnancy tests performed within 24 hours of administration of EMI-137 Injection. * Pre-menopausal female participants of child-bearing potential who agree to employ two method of contraception (as defined in eligibility criteria of the protocol) during the study period and for 90 days after EMI-137 administration. * Male participants with a non-pregnant female partner. Male participants with a pre-menopausal partner of child-bearing potential who agree to use two forms of contraception (as defined in section 8.2) during the study period and for at least 90 days after receiving EMI-137. (The only permissible exception would be if the participant had undergone documented bilateral orchidectomy or their female partner is post-menopausal (cessation menses >1 year) or has undergone documented bilateral oophorectomy and/or hysterectomy). Exclusion Criteria: * Patients who are participating in another intra-operative fluorescence study, or have participated in another fluorescence study within 3 months of the planned surgical procedure. * Received an investigational medicinal product at any dose within 28 days of planned EMI-137 administration * Patients with pre-existing inflammatory bowel disease. * Patients who have undergone neoadjuvant chemotherapy to treat the colon cancer. * Patients with impaired renal function (eGFR <60 mls/min/1.73m2). * Patients with impaired liver function (Bilirubin above institutional limits and/or ALT >2.5x upper limit of normal). * Pregnant and breastfeeding woman. * Pre-menopausal woman planning to become pregnant within 90 days of receiving EMI-137; or pre-menopausal woman of child-bearing potential who refuse to use two forms of contraception for at least 90 days after receiving EMI-137. * Male patients with a currently pregnant partner or male patients who are planning to conceive a pregnancy with a female partner within 90 days of receiving EMI-137; or male participants who refuse to use two forms of contraception as defined in section 8.2 for at least 90 days after receiving EMI-137 with their female partner of child-bearing potential. * Poorly controlled or serious medical or psychiatric illness that, in the investigator's opinion, is likely to interfere with participation and/or compliance in this clinical trial. * Previous adverse reaction to fluorescent agents.

Study Objectives Phase II Trial of concurrent administration of intravesical BCG \& Interferon in the treatment and prevention of recurrence of superficial transitional carcinoma of the urinary bladder. Conditions: Transitional Carcinoma of Urinary Bladder Intervention / Treatment: DRUG: BCG, Interferon Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with superficial transitional carcinoma of the urinary bladder

Study Objectives To investigate clinical positioning between trastuzumab (Herceptin) monotherapy (H group) and combination therapy of trastuzumab and chemotherapy (H+CT group) based on a randomized controlled trial in women over 70 years with human epidermal growth factor receptor type-2 (HER2) positive primary breast cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: trastuzumab monotherapy, DRUG: trastuzumab and chemotherapy Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer. * Stage: 1 (tumor size \[pT\] > 0.5 cm), 2A, 2B or 3A/ M0 * Female between 70 and 80 years old * Primary region is HER 2 positive: either 3+ overexpression by IHC or positive by FISH * Baseline left ventricular ejection fraction (LVEF) is ≥55% measured by echocardiography or MUGA scan within 4 weeks before registration. * PS: 0-1 (ECOG) * Sufficient organ function meeting following criteria within 4 weeks before registration: * Leukocyte ≥2500 mm3 * Neutrophil ≥1500 mm3 * Platelet ≥100 000 mm3 * Serum total bilirubin ≤2.0 x upper limit of normal (ULN) * ALT (GPT) or AST (GOT) ≤2.5 x ULN * Serum creatinine ≤2.0 x ULN * ALP ≤2.5 x ULN * No previous endocrine therapy or chemotherapy for breast cancer * Signed written informed consent Exclusion Criteria: * Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs) * Postoperative histological axillary lymph node metastasis ≥4 * Axillary lymph node is not histologically evaluated * Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on policy of site) * History of drug-related allergy which could hinder planned treatment * Any history or complication of following cardiac disorders * History of congestive heart failure, cardiac infarction * Complication requires treatment such as: ischemic cardiac disorder, arrhythmia, valvular heart disease * Poorly controlled hypertension (ex. Systolic arterial pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg) * Poorly controlled diabetes * Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living (ADL) * Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms * Ineligible to the trial based on decision of an investigator

Study Objectives This study is designed to evaluate the ability of intravenously (IV)administered 131-I-labeled TM-601 (chlorotoxin) to provide tumor-specific localization(via radiographic imaging) in patients with recurrent or refractory primary solid tumors with evidence of metastatic involvement. (Refractory tumors are non-responsive to standard treatment.) The safety and tolerability of IV administered 131-I-TM-601 in this patient population will be evaluated as part of this study. Conditions: Breast Cancer, Non-Small Cell Lung Cancer, Melanoma, Colorectal Cancer, Pancreatic Cancer, Prostate Adenocarcinoma, Glioma, Primary Solid Tumors Intervention / Treatment: DRUG: 131-I-TM-601 (chlorotoxin) 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: * Histologically confirmed recurrent or refractory primary solid tumor malignancy. Primary tumor cell type is one of the following: breast, non-small cell lung, melanoma, colorectal, prostatic adenocarcinoma (hormone refractory) or glioma. Note: Patients with a primary solid tumor cell type not listed above, meeting all other selection criteria may be considered eligible, on a case by case basis * Demonstration of distant metastatic involvement as seen with standard clinical non-invasive imaging techniques (CT/MRI) or on biopsy. Note: on a case-by-case basis, patients with a locally recurrent, unresectable (inoperable) tumor may be considered for inclusion * Refractory to standard curative treatment * At least 18 years of age * Baseline Karnofsky Performance Status (KPS) of 60-100% * Life expectancy, based on investigator judgement, of greater than 3 months * Adequate organ and marrow function (as defined in protocol) * Women of child-bearing potential must have a negative pregnancy test, refrain from nursing, and must agree to use appropriate contraception for the duration of the trial Exclusion Criteria: * Prior cytotoxic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study * Patients who have not sufficiently recovered from adverse events due to previously administered agents * Concurrent treatment with investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy, including chemotherapy, immunotherapy, biological response modifiers, or palliative radiotherapy. Possible exceptions (at the discretion of the investigator) are for hormonal therapy for breast and prostate cancer, hematologic, analgesic, biphosphonate, and any other form of supportive therapy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to 131-I-labeled chlorotoxin (e.g. iodine or iodine-containing drugs) * Patients with uncontrolled intercurrent illness.

Study Objectives The goal of this clinical research study is to learn if temozolomide alone or given with pegylated interferon alpha-2b can help to control metastatic melanoma. Researchers also want to study the safety of these 2 treatments. Objectives: 1. To determine the anti-tumor activity (pathological response CR+PR) and toxicity of temozolomide (TMZ) alone or in combination with pegylated interferon alpha-2b (PGI) in patients with resectable stage IIIC or stage IV (M1a) metastatic melanoma prior to definitive surgical resection. 2. To determine the relapse-free survival, overall survival and the impact of tumor response to chemotherapy in these patients. 3. To differentiate the in vivo treatment effects of TMZ alone vs.TMZ plus PGI and correlate with clinical outcome by analysis the pre- and post-treatment tumors and peripheral blood mononuclear cells with respect to: 1) Known cellular and molecular markers of apoptosis and cell proliferation, 2) Promotor methylation status of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), 3) DNA sequence variability of tumor suppressor genes and DNA repair enzymes, 4) Tumor genomic expression profiles analysis by complementary DNA (cDNA) microarray and protein array Conditions: Melanoma Intervention / Treatment: DRUG: Temozolomide (TMZ), DRUG: Pegylated Interferon Alpha-2b (PGI) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Histologically documented diagnosis of melanoma metastases. * Stage IIIB/IIIC (N2b, N2c and N3) or stage IV (M1a) melanoma patients with measurable and potentially resectable metastases without clinical and radiological evidence of other distant metastases. * An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Age 18 or older. * Adequate organ function defined as follows: a.) Absolute granulocytes greater than or equal to 1,000/mm\^3 and Platelets greater than or equal to 100,000/mm\^3, b.) Serum bilirubin and serum creatinine of less than or equal to 1.5 times upper limit of laboratory normal. If serum creatinine is greater than 1.5 times upper limit of laboratory normal, the urine creatinine clearance must be greater than 60 ml/min., c.) serum glutamate oxaloacetate transaminase (SGOT) (AST), serum glutamate pyruvate transaminase (SGPT) (ALT) and alkaline phosphatase less than or equal to 3 times upper limit of laboratory normal. * Patients have not had any previous systemic chemotherapy for metastatic melanoma. Prior biologic therapy, targeted therapy or immunotherapy are allowable, but must be at least 2 weeks since prior therapy before starting study drugs. No other concurrent chemotherapy, immunotherapy, or radiotherapy. * Prior radiation therapy used to enhance local regional control is permitted, but must be at least 2 weeks since prior therapy before starting study drugs. In addition, the patient must have unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity. Lesions within the prior field of radiation may only be used as indicator lesions if there has been recent evidence of disease progression after . * Ability to understand and sign an informed consent form, indicating awareness of the investigational nature of this study. Exclusion Criteria: * Significant cardiac or pulmonary dysfunction, such as a history of severe cardiovascular disease, myocardial infarction within 6 months of the start of treatment, unstable angina, Class III or Class IV congestive heart failure, ventricular arrhythmia, or any uncontrolled arrhythmia. * Current significant psychiatric illness. * Serious infection requiring intravenous antibiotics, or any non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by complications of this therapy. * Frequent vomiting or any medical condition (e.g. partial bowel obstruction) that could interfere with oral medication intake. * Autoimmune or immunosuppressive disorders (e.g. HIV or AIDS-related illness). * Patients who require therapy with systemic corticosteroids. * No evidence of active secondary malignancy that requires chemotherapy within the past 2 years (excluding non-melanoma skin cancer, and/or all carcinoma in-situ) * Pregnant or lactating women are ineligible. Women of childbearing potential must have a negative urine pregnancy test within a week of initiation of therapy. All patients must agree to use medically approved contraceptive measures to prevent pregnancy during treatment. * Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial.

Study Objectives The current standard treatment of inoperable intrahepatic cholangiocarcinoma (bile duct cancer in the liver) is chemotherapy, which is of limited efficacy. The use of selective internal radiotherapy treatment (SIRT-Y90) is proven efficacious in patients with intra-heptic tumor. Previous experience with SIRT is safe in patients with intrahepatic cholangiocarcinoma. This study aims to study the benefits of sequential administration of SIRT followed by standard chemotherapy for treatment of inoperable intrahepatic cholangiocarcinoma. Conditions: Cholangio Carcinoma Intervention / Treatment: DRUG: SIRT Yttrium-90 Location: Hong Kong Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age>18 years * Histological or cytological diagnosis of cholangiocarcinoma * Disease not amenable to surgery * Predominant disease load in the liver (in case of extra-hepatic involvement, only patients with lymph nodes metastases are allowed) * Naïve to locoregional or systemic treatment (but patients who develop recurrent disease after surgery are suitable) * ECOG PS 0-1 * At least one measurable disease lesion according to RECIST v 1.1 * Life expectancy of 12 weeks or longer * Adequate hematological, renal and hepatic function * Platelet ≥100 x 109 * ANC ≥ 1.5 x 109 * Bilirubin ≤ 30µmol/L * Albumin ≥ 30g/L * ALT ≤ 3 ULN * INR ≤ 1.5 * Serum creatinine ≤ 1.5 x ULN Exclusion Criteria: * Prior malignancy except cervical carcinoma-in-situ or treated basal cell carcinoma. Any cancers treated curatively > 5 years prior to study entry are permitted. * Patients with extra-hepatic disease other than regional lymph node metastases. * Evidence of ascites or cirrhosis, as determined by clinical or radiologic assessment * Biliary obstruction with no possibility of drainage * Non-malignant disease that would render the patient unsuitable for treatment according to the protocol * Prior treatment of chemotherapy for the cholangiocarcinoma * Prior radiation therapy to the upper abdomen * Complete thrombosis of the main portal vein * Tumor volume > 50% of the normal liver volume * Allergy to non-ionic contrast agents

Study Objectives AIM OF STUDY Primary Efficacy Variable: The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer. Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death. Secondary Efficacy Variables: * Clinical benefit (CR+PR+SD) * ORR (CR+PR) * Time to progression * Time to next Treatment (TTT) * Overall survival * Safety profile Conditions: Metastatic Breast Cancer Intervention / Treatment: DRUG: Paclitaxel and Sorafenib, DRUG: Paclitaxel Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the breast * HER-2/neu negative (primary tumour site HER-2/neu negative by ICH/FISH test) * Second till third-line of chemotherapy * Female, age ≥ 18 years. * ECOG Performance Status of 0 or 1 (Karnofsky-Index ≥ 70%) * Life expectancy of at least 12 weeks. * Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by Xray (pulmonary lesions only) or CT-scan or MRI (Patients with only measurable bone lesions can be also included, as long they meet the criteria for RECIST 1.1.; means, lytic bone lesions or mixed lytic-blastic bone lesions with identifiable soft tissue components.) * No prior therapy for locally recurrent or metastatic disease with TKI's (RAS/Raf, MEK, AKT), mTOR inhibitors and angiogenesis inhibitors (VEGV/VEGFR, PDGF/PDGFR) but bevacizumab will be allowed. * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: * Hemoglobin ≥ 9.0 g/dl * Absolute neutrophil count (ANC) ≥ 1,500/mm3 * Platelet count ≥ 100,000/μl * Total bilirubin ≤ 1.5 x upper limit of normal * ALT and AST ≤ 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer) * Alkaline phosphatase ≤ 4 x upper limit of normal * PT-INR and PTT ≤ 1.5 x upper limit of normal \[Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.\] * Serum creatinine ≤ 1.5 x upper limit of normal. * Signed and dated informed consent before the start of specific protocol procedures. Exclusion Criteria: * History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. * Known history of HIV infection or chronic hepatitis B or C * Active clinically serious infections (> grade 2 NCI-CTC version 4.02) * Prior clinical or radiological evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by contrast enhanced head CT scan or MRI * Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) * History of organ allograft * Patients with evidence or history of bleeding diathesis * Patients undergoing renal dialysis * Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours \[Ta, Tis \& T1\] or any cancer curatively treated > 3 years prior to study entry. * Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial. * Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results * Any condition that is unstable or could jeopardise the safety of the patient and their compliance in the study * Patients unable to swallow oral medications. * Patients with intolerance to Paclitaxel. Excluded therapies and medications, previous and concomitant: * Anticancer chemotherapy, hormonotherapy or immunotherapy during the study or within 3 weeks of study entry. * Radiotherapy within 3 weeks of start of study drug, palliative radiotherapy will be allowed. * Major surgery within 4 weeks of start of study * Autologous bone marrow transplant or stem cell rescue within 4 months of study entry * Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. \[G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.\] \[Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study\] * Investigational drug therapy outside of this trial during or within 4 weeks of study entry * Previous treatment with paclitaxel within 1.line and 2.line palliative therapy (Paclitaxel within (neo-) adjuvant therapy is allowed)

Study Objectives This randomized clinical trial studies radiation therapy and MK-3475 in treating patients with head and neck cancer, kidney cancer, melanoma, or lung cancer that has returned, has spread to other parts of the body, or cannot be removed by surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as MK-3475, may block tumor growth by targeting certain cells and causing the immune system to attack the tumor. Studying the effects of MK-3475 with radiation therapy on the body may help doctors learn whether it may be an effective treatment for these solid tumors. Conditions: Head and Neck Squamous Cell Carcinoma, Metastatic Renal Cell Cancer, Recurrent Head and Neck Carcinoma, Recurrent Lung Carcinoma, Recurrent Renal Cell Carcinoma, Recurrent Skin Carcinoma, Stage III Renal Cell Cancer, Stage IV Lung Cancer, Stage IV Skin Melanoma Intervention / Treatment: RADIATION: Radiation Therapy (RT), DRUG: MK-3475 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Be willing and able to provide written informed consent/assent for the trial. * Be ≥ 18 years of age on day of signing informed consent. * Have provided tissue from an archival tissue sample ( < 6 months old) or newly obtained core biopsy of a tumor lesion before radiation therapy. A core biopsy will be required. It is mandatory to have post-radiation re-biopsy. * In addition to index lesion, there are ≥ 1 measurable lesion(s). * Have a performance status of ≤ 1 on the ECOG Performance Scale. * Demonstrate adequate organ function defined as the following: * Absolute neutrophil count (ANC) ≥1,500 /mcL * Platelets ≥100,000 / mcL * Hemoglobin ≥9 g/dL or ≥5.6 mmol/L * Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.8 X upper limit of normal (ULN) OR ≥50 mL/min for subject with creatinine levels > 1.8 X institutional ULN * Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases * Female subjects of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: * Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the radiation therapy. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the radiation therapy. * Has had a prior monoclonal antibody within 4 weeks prior to radiation therapy or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to radiation therapy or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. * Note: Prior radiation therapy does not necessary excludes patients. The index lesion may be acceptable for stereotactic radiosurgery (SRS) and this will be determined by radiation oncologist. * Note: If there are more than one symptomatic lesions, patients will be excluded if the lesions can't be encompassed within one radiation portal. * Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the radiation therapy and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to radiation treatment. * Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. * Has evidence of interstitial lung disease or active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). * Has a known Human Immunodeficiency Virus infection (HIV 1/2 antibodies) or Acquired Immunodeficiency Syndrome((HIV/AIDS). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days prior to the radiation therapy.

Study Objectives The goal of this clinical trial is to learn the comparative pharmacokinetic parameters between the test product and the Reference listed drug in healthy female volunteers The main question\[s\] it aims to answer are: * To assess the sequential dose exposure safety and tolerability of KSHN001034 injection in healthy female subjects after single ascending doses from 25 mg to 500 mg and multiple doses of maximum tolerable dose from single ascending dose * To assess dose showing comparative bioavailability of KSHN001034 injection in comparison with Faslodex®. Conditions: Metastatic Breast Cancer Intervention / Treatment: DRUG: Fulvestrant injection Location: Jordan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * The subject is healthy female adult of population aged between 40 to 60 years old (inclusive) at screening. * The subject has a body weight not less than 50 Kg and according to the BMI range (18.5 - 30 Kg/m2)6 (inclusive) at screening. * The subject is fully vaccinated for COVID-19 at least two weeks ago, as checked at screening. -. The subject is physically and mentally healthy as judged by means of medical and standard laboratory examinations at screening. * The findings of the subject are within the range of clinical acceptability in medical history, and physical examination, and laboratory results "other than RBC indices (MCH, MCV and MCHC), and hemoglobin, " within "normal ranges" for the laboratory tests performed or abnormalities considered insignificant and justified by the principal/clinical sub- investigator at screening. * The subject results are within normal range or ± 5% of medical lab reference range for all RBC indices (MCH, MCV and MCHC) and hemoglobin, at screening -. The subject's platelets count is within medical lab reference range at screening. * The subject has a normal ECG (12 leads), including normal QTc (below 440 msec), at screening * The subject's chest X-ray, performed within 6 months before screening (if available) or at screening, is normal or considered clinically acceptable with no evidence of ongoing or past serious infections, as per the investigator judgment at screening. * The subject vital signs in sitting position are within the following ranges at screening, and on admission day (before admission): Blood Pressure: Systolic: (90 - 140) mmHg Diastolic: (60-90) mmHg Body Temperature: (36.1 - 37.2) ºC Pulse rate: 60 to 100 beat per minute. Respiratory rate: 12-18 bpm. * Kidney function tests (Creatinine, Potassium and Sodium) are within the medical lab reference range and kidney function tests (Blood Urea Nitrogen, and uric acid) are considered clinically acceptable as per the investigator judgment at screening. If creatinine is below the lower normal limit while the other parameters are normal, it will be considered as clinically not significant unless otherwise judged by the investigator. * Liver function tests (AST, ALT, GGT, and bilirubin (total, direct, and indirect)) results are within the medical lab reference ranges and liver function tests (Alkaline phosphatase, total protein, and albumin) are considered clinically acceptable as per PI / SI judgment at screening. Exclusion Criteria: * The subject has an evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of the consent to participation in the study or limit the ability to comply with the protocol requirements, as determined by the principal investigator/clinical Sub-investigator at screening or on admission day (before admission). * The subject has a known history or presence of any clinically significant abnormality / pathology / disease in any of the body systems, as checked at screening or on admission day (before admission). * The subject has a clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, active inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), short bowel syndrome, upper gastrointestinal surgery including gastric resection, or other conditions known to interfere with the metabolism or excretion of the drug as determined by the principal investigator/clinical sub-investigator at screening or on admission day (before admission). * The subject has a history of allergy or major allergic reactions or known allergy/ hypersensitivity to the drug under investigation (Fulvestrant), or to any of the excipients (ethanol, benzyl alcohol, benzyl benzoate, castor oil refined), as checked at screening * The subject has a history of hypersensitivity to heparin as checked at screening. * The subject has a history of vaginal bleeding or discharge, bleeding diatheses, thrombocytopenia or taking anticoagulant treatment as checked at screening. * The subject has symptoms suggestive of COVID-19 as judged by the principal investigator/clinical sub-investigator at screening or admission day (before admission). The subject is pregnant or nursing (lactating) women, where pregnancy is defined as the state of the female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test at screening or on admission day (before admission). * The subject has consumed or does not agree to abstain from consuming any beverages or food containing alcohol from screening until donating the last PK sample of the study cohort, as checked at screening or on admission day (before admission). * The subject does not agree to abstain from consuming any beverages or food containing methylxanthines e.g. caffeine (coffee, tea, cola, energy drinks, chocolate, ...etc) for at least 24 hours prior to each dosing and for 24 hrs after each dosing, as checked at screening or on admission day (before admission). * The subject has taken any prescribed drugs within four weeks preceding first study drug administration or doesn't agree on not taking them until donating last PK sample of the study cohort, as checked at screening or on admission day (before admission).

Study Objectives Given the lack of other viable treatment options for metastatic neuroendocrine tumors, contrasted with our positive anecdotal experience, and the relative tolerability of the treatment regimen for colorectal cancer patients, we propose a single-institution phase II trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors. Conditions: Neuroendocrine Tumors Intervention / Treatment: DRUG: Capecitabine, DRUG: Oxaliplatin, DRUG: Bevacizumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Subjects must be treated at Stanford University Medical Center for the entire length of study participation. * Patients must have histologically or cytologically confirmed neuroendocrine tumor, including both well-differentiated tumors (carcinoid) or moderately to poorly differentiated tumors. Patients must be deemed unresectable due to involvement of critical vasculature, adjacent organ invasion, or presence of metastasis. * Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases. * Prior chemotherapy will be permitted, although the patient may not have had prior oxaliplatin. * Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (see Section 4.2) within 4 weeks prior to entry of study * Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Patients must be ≥ 18 years of age * Laboratory values ≤ 2 weeks prior to randomization: * Absolute Neutrophil Count (ANC) >=1500/mm3 * Platelets (PLT) ≥ 100,000/mm3 * Hemoglobin (Hgb) ≥ 9 g/dL * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) * Serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if liver metastases present) * Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and alkaline phosphatase ≤ 3.0 x ULN (≤ 5.0 x ULN if liver metastases present). Note: Endoscopic retrograde cholangiopancreatogram (ERCP) or percutaneous stenting may be used to normalize the liver function tests. * Life expectancy ≥ 12 weeks * Ability to give written informed consent according to local guidelines Exclusion Criteria:- Disease-Specific Exclusions * Prior oxaliplatin for any reason. * Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease. * Prior biologic or immunotherapy ≤ 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities * Prior therapy with anti-vascular endothelial growth factor (VEGF) agents * If history of other primary cancer, subject will be eligible only if she or he has: * Curatively resected non-melanomatous skin cancer * Curatively treated cervical carcinoma in situ * Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years * Concurrent use of other investigational agents and patients who have received investigational drugs ≤ 4 weeks prior to enrollment. * General Medical Exclusions * Subjects known to have chronic or active hepatitis B or C infection 2. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results 3. Male subject who is not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of second-line treatment 4. Female subject (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) who is not willing to use an oral, patch or implanted contraceptive, double-barrier birth control, or an intrauterine device (IUD) during the course of the study and for 6 months following the last dose of second-line treatment 5. Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization 6. Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea) 7. Any of the following concurrent severe and/or uncontrolled medical conditions within 24 weeks of enrollment which could compromise participation in the study: * Unstable angina pectoris * Symptomatic congestive heart failure * Myocardial infarction ≤ 6 months prior to registration and/or randomization * Serious uncontrolled cardiac arrhythmia * Uncontrolled diabetes * Active or uncontrolled infection * Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung * Chronic renal disease * Acute or chronic liver disease (eg, hepatitis, cirrhosis) 8. Patients unwilling to or unable to comply with the protocol 9. Life expectancy of less than 12 weeks 10. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study * Bevacizumab-Specific Exclusions 1. Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications) 2. Any prior history of hypertensive crisis or hypertensive encephalopathy 3. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E) 4. History of myocardial infarction or unstable angina within 6 months prior to study enrollment 5. History of stroke or transient ischemic attack within 6 months prior to study enrollment 6. Known central nervous system (CNS) disease 7. Significant vascular disease (eg, aortic aneurysm, aortic dissection) 8. Symptomatic peripheral vascular disease 9. Evidence of bleeding diathesis or coagulopathy 10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study 11. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment 12. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment 13. Serious, non-healing wound, ulcer, or bone fracture 14. Urine protein ≥ 2+ on urinalysis dipstick and ≥ 1.0 gram on 24-hour urine collection 15. Known hypersensitivity to any component of bevacizumab

Study Objectives The purpose of this study is to collect some parameters which may help to provide guidance on how Androgen Deprivation Therapy (ADT) drugs are renewed and physician satisfaction. Conditions: Prostate Cancer Intervention / Treatment: DRUG: triptorelin Location: Romania Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Adult men, ≥18 years old, with recently diagnosed locally advanced or metastatic prostate cancer scheduled to receive androgen deprivation therapy as monotherapy or as concomitant and adjuvant therapy in association with radiation therapy, with a 1 or 3 month GnRH analogue triptorelin formulation * Expected survival > 12 months. * Patients having provided written informed consent. * Patients mentally fit for completing a questionnaire. Exclusion Criteria: * Treatment with any investigational drug within the last 3 months before study entry or planning to participate in a study. * Patients who already have been treated with a GnRH analogue within the last year. * Patients with hypersensitivity to GnRH, GnRH analogue, triptorelin or its excipients. * Patients with a contraindication according to SmPC.

Study Objectives Investigating the safety and the activity of Rapamycin, administered before and during preoperative radiotherapy in patients with an operable colorectal carcinoma. The phase I dose escalation study will be performed in three steps (2, 4 and 6 mg). Patients entered in phase II will follow the same tolerable treatment regimen as patients in phase I study. Conditions: Rectum Cancer Intervention / Treatment: DRUG: Rapamycin Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically proven rectum cancer * UICC TNM I-III * WHO performance status 0-2 * Less than 10% weight loss the last 6 months * No recent (< 3 months) severe cardiac disease * Normal serum bilirubin and serum creatinin Exclusion Criteria: * Concurrent chemotherapy with radiation * History of prior pelvis radiotherapy * Recent (<3 months) myocardial infarction * Uncontrolled infectious disease * Concurrent medication known as inhibitors of CYP3A4 susceptible to increase Rapamycin blood concentrations

Study Objectives The aim of the study is to determine the optimal dose of the combination of docetaxel and gemcitabine in patients with hormone refractory prostate cancer, and evaluate this dose with respect to efficacy and toxicity in a phase II trial. Conditions: Prostate Cancer Intervention / Treatment: DRUG: docetaxel, DRUG: gemcitabine Location: Denmark 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 verified adenocarcinoma of the prostate. * Hormone refractory prostate cancer (HRPC) defined as progression during previous anti-hormone treatment. Patients must have been off previous anti-androgen therapy for more than 4 weeks. * Stage IV disease (verified by imaging or clinical examination). * PSA > 10 microgram/l. * PSA progression defined as a > 25% increase between two independent measurements performed with a 1-month interval or more after discontinuation of anti-androgen treatment. * Castrate level of testosterone (< 50 ng). * No previous oestrogen or steroid as metastatic prostate cancer treatment. * Satisfactory hepatic function in the form of total bilirubin ≤ UNL (upper normal limit), ASAT/ALAT ≤ 2.5 x UNL, alkaline phosphatase ≤ 5 x UNL. * Satisfactory renal function, defined as serum creatinine ≤ 1.5 x UNL. * Satisfactory haematologic function defined as ANC >1.5 x 10\^9/l, leucocytes >3.0 x 10\^9/l, thrombocytes ≥ 100 x 10\^9/l, haemoglobin > 7 mmol/l * ECOG performance status ≤ 2. * Life expectancy > 3 months. * Patient must be able to adhere to protocol requirements. * Written informed consent. * > 18 years of age. Exclusion Criteria: * Previous prostate cancer treatment with oestrogens or steroid hormones. * Previous chemotherapy. * Previous treatment with systemic radioactive isotopes. * Bisphosphonate treatment (concomitant). * Radiation therapy covering more than 25% of the bone marrow producing area. * Other serious coincidental and/or concomitant medical condition. * Symptomatic cerebral metastases. * Other previous or current malignant disease, excluding \*adequately treated and cured planocellular skin carcinoma; or \*other cancer assessed to carry minimal risk of recurrence. * ECOG performance status > 2.

Study Objectives This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with S-1 CCRT for locally advanced NPC. Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count, normal hepatic function and normal renal function. Prior induction chemotherapy with platinum was allowed. Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to S-1; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement. The full-set pretreatment evaluation will be performed to every patient.All patients in this study will receive intensity-modulated radiation therapy (IMRT). During the IMRT course, S-1 will be administered orally according to body surface area.The dose modifications of S-1 will not be permitted during concurrent chemotherapy unless progression of the disease, toxicities of grade 4 or patient's refusal. The primary endpoints of this study is adverse events (AE) rate and progression-free survival (PFS). Conditions: Nasopharyngeal Carcinoma Intervention / Treatment: DRUG: S-1 Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed locally advanced NPC * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; * Normal complete blood count * Normal hepatic function * Normal renal function (creatinine ≤ 1.5 times the upper limit of normal). Exclusion Criteria: * Previous radiotherapy * A history of any other type of malignancy * Pregnancy or lactation * Allergy to S-1 * Obvious disfunction of liver, renal, cardiac or lung function * Uncontrolled infection * Systemic metastasis or distant metastasis * Patients with severe gastrointestinal diseases * Patients with mental disorders affecting patient participation in trial judgement.

Study Objectives This Phase 2 study is an open-label, single-arm trial where each patient is his/her own "intrapatient" control. All patients will receive a single dose of pegsitacianine prior to standard of care surgery. Conditions: Lung Cancer Intervention / Treatment: DRUG: pegsitacianine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Biopsy confirmed diagnosis, or a high clinical suspicion of a lung malignancy based on MRI, CT and/or PET imaging Exclusion Criteria: * Known hypersensitivity or allergy to indocyanine green (ICG), polymethylmethacrylate (PMMA; found in dental and bone cements) or polyethylene glycol (PEG) * Tumor locations the surgeon deems unfeasible to image intraoperatively * Excessive and/or generalized disease deemed inoperable by the surgeon * Life expectancy less than 12 weeks

Study Objectives This phase II trial is studying how well CCI-779 works in treating patients with stage IIIB non small cell lung cancer (with pleural effusion) or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop tumor cells from dividing so they stop growing or die. CCI-779 may also stop the growth of tumor cells by blocking the enzymes necessary for their growth. Conditions: Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer Intervention / Treatment: DRUG: temsirolimus, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) * Stage IIIB (with pleural effusion) or IV disease * Measurable disease * At least 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan * The following are not considered measurable disease: * Bone lesions * Leptomeningeal disease * Ascites * Pleural/pericardial effusion * Inflammatory breast disease * Lymphangitis cutis/pulmonis * Cystic lesions * Abdominal masses that are not confirmed and followed by imaging techniques * Blood and tissue blocks available * Must have accessible tumor (i.e., superficial lesions such as lymph node, subcutaneous nodules) to provide core needle biopsy tissue before and during study treatment * No known brain metastases * Performance status - ECOG 0-2 * At least 12 weeks * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL * Bilirubin ≤ 2 times upper limit of normal (ULN) * AST ≤ 3 times ULN (5 times ULN if hepatic metastases are present) * Creatinine ≤ 1.5 times ULN * Serum fasting cholesterol ≤ 350 mg/dL * Serum fasting triglycerides ≤ 400 mg/dL * HIV negative * No uncontrolled infection * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or non-invasive carcinomas * No concurrent severe underlying disease that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study treatment * No prior biologic therapy * No prior gene therapy * No prior immunotherapy * No concurrent immunotherapy * No concurrent prophylactic growth factors to support neutrophil count * No prior chemotherapy for NSCLC except low-dose cisplatin as a radiosensitizer * No other concurrent chemotherapy * No concurrent dexamethasone (10 mg IV) * No prior radiotherapy to 30% or more of bone marrow * Concurrent radiotherapy for underlying malignancy and non-target sites (e.g., painful pre-existing bony metastasis) allowed * No other concurrent investigational therapy * No concurrent immunosuppressive therapy

Study Objectives This study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK (pharmacokinetics) of oral AMG 900 in subjects with acute myeloid leukemia. Up to 93 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 20 subjects with acute myeloid leukemia. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study. Conditions: Cancer, Hematologic Malignancies, Leukemia, Myeloid Leukemia Intervention / Treatment: DRUG: Arm 1- Dose Escalation, DRUG: Arm 2- Dose Expansion 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: * Men or women ≥ 18 years old * Pathologically documented, definitively diagnosed AML that has failed standard treatments or for which no standard therapy is available or the subject refuses standard therapy * Must consent to undergo bone marrow biopsies per schedule of assessments Exclusion Criteria: * White blood cell greater than 20,000 uL * History of or active central nervous system leukemia * Prior allogeneic bone marrow transplant * Subject will not be available for protocol-required study visits or procedures Other Inclusion/ Exclusion Criteria may apply to qualify for enrollment

Study Objectives This phase II trial studies how well giving paclitaxel albumin-stabilized nanoparticle (Nab-paclitaxel) formulation together with bevacizumab followed by bevacizumab and erlotinib hydrochloride work in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can prevent cancer growth by blocking the ability of cancer cells to grow and spread. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial evaluates a maintenance treatment with erlotinib and bevacizumab after Nab-paclitaxel and bevacizumab which may control cancer growth with biologic therapies. Conditions: Estrogen Receptor-negative Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-negative Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer, Triple-negative Breast Cancer Intervention / Treatment: DRUG: paclitaxel albumin-stabilized nanoparticle formulation, BIOLOGICAL: bevacizumab, DRUG: erlotinib 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: * Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) * Be receiving first-line therapy for metastatic disease * Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration * OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL * Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment * Bilirubin =< 1.5 mg/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis * Alkaline phosphatase =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis * Platelets > 100,000 cells/mm\^3 * Hemoglobin > 9.0 g/dL * Absolute neutrophil count (ANC) >= 1,500 cells/mm\^3 * Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable * If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy * Pre-existing peripheral neuropathy, if present, must be < grade 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0) * Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines Exclusion Criteria: * Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane * Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids * Pre-existing nephritic syndrome * Serious intercurrent medical or psychiatric illness including serious active infection * Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications) * Any prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to study enrollment * History of stroke or transient ischemic attack within 6 months prior to study enrollment * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Serious, non-healing wound, ulcer, or bone fracture * Proteinuria at screening as demonstrated by either: * Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR * Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is < 1.0 to be eligible; if the UPC ratio is >= 1.0 then the patient should undergo a 24-hour urine collection which must demonstrate =< 1 g of protein in 24 hours for the patient to be eligible) * Known hypersensitivity to any component of bevacizumab or to nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation)

Study Objectives This is a study to evaluate the safety and pharmacokinetics in pediatric patients with secondary hyperparathyroidism receiving a single dose of etelcalcetide at the end of hemodialysis. Conditions: Chronic Kidney Disease, Secondary Hyperparathyroidism Intervention / Treatment: DRUG: Etelcalcetide Location: Germany, Lithuania, United Kingdom, United States, Belgium, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Subject's parent has provided informed consent and subject has provided assent * Children Age 2 to less than 18 years * Diagnosed with chronic kidney disease * Diagnosed with secondary hyperparathyroidism receiving hemodialysis, * Weighing at least 7 kg * Laboratory results within specified range. Exclusion Criteria: * Currently receiving treatment in another investigation device or drug study * Subject has received cinacalcet therapy within 30 days * History of prolongation QT interval * Subject is taking any medications that are on the QT prolongation medication list * Electrocardiograph (ECG) measurements within specified range.

Study Objectives The goal of this clinical research study is to learn if lenalidomide (Revlimid®) can help to control CLL in patients who have already received standard therapy. The safety of lenalidomide will also be studied. Conditions: Chronic Lymphocytic Leukemia, Leukemia Intervention / Treatment: DRUG: Lenalidomide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with B-cell CLL with indications for treatment by National Cancer Institute (NCI) Working Group Criteria, or Rai Stage III or IV or patients with CLL requiring treatment because of any of the following: disease related symptoms, progressive marrow failure (development or worsening of anemia and/or patients' thrombocytopenia) progressive splenomegaly, progressive lymphoadenopathy, progressive lymphocytosis * Patients who have received a minimum of one prior purine analog-based chemotherapy regimen. Prior treatment with corticosteroids, immunotherapy, monoclonal antibody or radiation therapy is permitted. All previous cancer therapy, including radiation, hormonal therapy and surgery must have been discontinued 2 weeks prior to treatment in this study. Any cytotoxic chemotherapy must be discontinued 4 weeks prior to treatment in this study. * Age more or equal to 18 years (CLL is not observed in patients less than 18 years of age). * Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status 0-2. * Adequate renal function indicated by serum creatinine less or equal to 2 and adequate hepatic function indicated as total bilirubin less or equal to 2 times the upper limit of normal. * Understand and sign Informed Consent after the investigational nature, study design, risks and benefits of the study have been explained. * Females of childbearing potential (FCBP)must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. * Continued from #7. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. * Continued from #8. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). * Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation can be enrolled in the study as long as they have a reasonable expectation to have been cured with treatment modality received. Exclusion Criteria: * Known sensitivity to thalidomide or its derivatives * The development of erythema nodosum as characterized by a desquamating rash while taking thalidomide or similar drugs. * Prior use of lenalidomide * Concurrent use of other chemotherapy agents. * Known positivity for Human immunodeficiency virus (HIV) or infectious hepatitis type A, B or C. * Pregnant or lactating females. * A serious medical condition, laboratory abnormality or psychiatric illness that would pose the subject at unacceptable risk if he/she were to participate in the study or that would interfere with the ability of the patient to carry out the treatment program or confine the ability to interpret the data from the study. * Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood). * Active cardiovascular disease as defined by the New York Heart Association class 3 or 4.

Study Objectives Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) is a mainstay for treating head and neck cancers, but elderly or fragile patients are often precluded because of the risk of severe toxicities associated with this protocol. DPD (Dihydro Pyrimidine Dehydrogenase) deficiency is a pharmacogenetic syndrome responsible for most of the severe/lethal toxicities showing in 5-FU (5-Fluorouracile)-treated patients, and our institute has developed a strategy for the routine determination of Dihydro Pyrimidine Dehydrogenase (DPD) status prior to starting giving the 5-FU so as to roughly adapt drug dosage according to the Dihydro Pyrimidine Dehydrogenase (DPD) status. This project aims at developing a Bayesian strategy to further individualize 5-FU dosing to reach a target exposure of area under curve (AUC). To this end, 100 patients with head and neck cancer and scheduled for a Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) regimen will be included. Conditions: Patients With Head and Neck Cancer (ORL) Intervention / Treatment: DRUG: Cisplatin, DRUG: Docetaxel, DRUG: 5-Fluorouracile Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age > 18 and ≤ 80 years. * Squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx). * Locally advanced stage (III, IVa or IVb). * The patient must have received the information note and signing the informed consent, as well as being spent in multidisciplinary meeting after which treatment with TPF (Docetaxel, Cisplatin, 5-Fluorouracile) induction chemotherapy was proposed. * Performance Status less than or equal to 2 (WHO performance index). * The patient must be affiliated to a social security scheme and followed in one of the participating centers. * Patients polymorphonuclear neutrophil greater than or equal to 1000 / mm3, platelets greater than or equal to 100 000 / mm3, hemoglobin greater than or equal to 8 g / dl, transaminases less than or equal to 1.5 times the normal, total bilirubin or equal 1.5 times the normal creatinine clearance in the upper or equal to 50 ml / min Modification of Diet in Renal Disease (MDRD) * Satisfactory heart function * Patients must be able to submit to the rhythm of visits, treatment plan, laboratory balances and other study procedures. Exclusion Criteria: * Patient > 80 years. * Patients with uncontrolled infection that could compromise participation in the study. * Patients with other serious concomitant diseases and / or uncontrolled that could compromise participation in the study. * Patients with serum bilirubin> under limit normal and / or Alanine Transaminase (ALAT) and Aspartate Transaminase (AST) 3.5 times the under limit normal with alkaline phosphatase greater than 6 times the under limit normal. * Cardiovascular disease or clinically significant cardiovascular disorder in the judgment of the investigator, such as, but not limited to uncontrolled hypertension, congestive heart failure The New York Heart Association (NYHA) classification> III), unstable angina, myocardial infarction in 6 months prior to treatment, uncontrolled arrhythmias, chronic liver or renal disease, severely impaired lung function. * Disorders significant acute gastrointestinal or recent with a major symptom of diarrhea, such as Crohn's disease, malabsorption syndrome or diarrhea Common toxicity Criteria for Adverse Events (CTCAE) grade> 1 whatever aetiology. * Performance Status and / or laboratory tests incompatible with chemotherapy using cisplatin, docetaxel and 5-fluorouracile (5-FU) * Inability to submit to medical monitoring test for geographical reasons, family, social or psychological. * Patients refusing to participate in biological assessments. * Persons deprived of liberty or guardianship. * Pregnant women or likely to be at the time of enrollment or during breastfeeding. * Free, informed and signed not obtained.

Study Objectives This is a Phase 1, open-label, non-randomized, dose-escalation study to determine the maximum tolerated dose (MTD), safety, tolerance, and pharmacologic profile of EZN-2968, a locked nucleic acid antisense oligonucleotide against hypoxia-inducible factor 1α administered as a 2-hour intravenous (i.v.) infusion weekly for 3 weeks per 6-week cycle. In patients treated at a recommended Phase 2 dose of EZN-2968, dose intensification will proceed by maintaining the dose, but gradually increasing the number of doses per 6-week cycle. Up to 3 intensification cohorts will receive the recommended Phase 2 dose of EZN-2968. Conditions: Carcinoma, Lymphoma Intervention / Treatment: DRUG: Intravenous EZN-2968 (anti-HIF-1α LNA AS-ODN) 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: Patients must meet all of the following criteria to be eligible for enrollment into the study. * Histologically or cytologically confirmed diagnosis of advanced and/or metastatic solid tumor or lymphoma (Hodgkin's or non-Hodgkin's) * Patients who have failed standard therapy and have no known effective therapy available to them * Patients may have a tumor amenable to biopsy * Measurable or evaluable disease. * Age 18 years or older Exclusion Criteria: Patients meeting any of the following exclusion criteria will not be eligible for enrollment. * Concurrent serious medical illness * Known, clinically suspected, or history of central nervous system (CNS) tumor involvement * Prior chemotherapy, immunotherapy, investigational agent, or other therapy used to treat the cancer within 4 weeks (6 weeks for prior treatment with mitomycin C or nitrosoureas) before the scheduled administration of EZN-2968. Luteinizing hormone-releasing hormone (LHRH) agonist therapy is permitted for patients with hormone refractory prostate cancer.

Study Objectives This is a retrospective biobank study evaluating the impact of novel genetic variants in a population of 6-mercaptopurine treated pediatric acute lymphoblastic leukemia patients. Conditions: Acute Lymphoblastic Leukemia, Pediatric, Adverse Drug Event Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Pediatric acute lymphoblastic leukemia (ALL) subjects * Received 6-mercaptopurine * Available biobank (bone marrow or blood) sample(s) from which deoxyribonucleic acid (DNA) can be extracted * White blood cell (WBC) levels Exclusion Criteria: * Pediatric ALL subjects who did NOT receive 6-mercaptopurine * No biobank sample * No WBC level

Study Objectives In a randomized study the investigators aim to characterize the effect of antidepressive medicine on quality of life, body composition, adrenal activity and glucose metabolism in PCOS. PCOS is a common endocrine disorder characterized by adrenal and ovarian hyperandrogenaemia, anovulation and insulin resistance. The pathogenesis of PCOS may be described by a vicious cycle involving insulin resistance which stimulates ovarian and adrenal hyper androgenaemia and leads to abdominal obesity, causing increased risk for diabetes and cardiovascular disease. Adrenal hyperactivity is associated with depression. Antidepressive medicine may normalize pituitary-adrenal activity and in animal studies antidepressive medicine improved adrenal hyperactivity and normalized insulin sensitivity. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DRUG: Escitalopram 20 mg, DRUG: Placebo Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * BMI > 25 and <5 * Age 18-45 years * Two of the following 1: an/oligomenorhea, 2: Hirsutism or hyper androgenaemia, 3: PCO in trans vaginal ultrasound * Other diagnoses excluded Exclusion Criteria: * Post menopausal * Diabetes * Eating disorder * Psychiatric disorder * Usage of oral anticonceptives or metformin * Pregnancy or planned pregnancy in the treatment period * Non-caucasian * Epilepsy * Allergy to the medicine

Study Objectives Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Transcatheter arterial chemoembolization (TACE) is the traditional method for the palliative management of patients with HCC. Few previous studies had demonstrated that the serum level of anticancer drug from patients treated by TACE was similar to those treated by systemic chemotherapy. The defense ability of the patient treated by TACE may thus be influenced by the leakage of anticancer drug to the systemic circulation. Since more than 80% patients with HCC also have liver cirrhosis, the toxicity for those anticancer drugs with hepatic transformation will be increased caused by the cirrhotic liver. The severity of pancytopenia in cirrhosis will be exacerbated by the effect of bone marrow suppression caused by anticancer drugs. Patients are at high risk for infection and hemorrhage. Therefore, it is of clinical importance to prevent or decrease the leakage of anticancer drugs to systemic circulation in patients treated by TACE. The procedures of TACE performed by previous studies were not constant and the distributions of tumor vessels were not evaluated in detail. The possible risk factors for the leakage of anticancer drug have not been investigated. This project will collect 60 patients with HCC including 30 patients with hepatitis B and 30 patients with hepatitis C. The blood levels of anticancer drugs (epirubicin, mitomycin C and cisplatin) will be determined within one hour and at the third day after TACE. Conditions: Hepatocellular Carcinoma Location: Taiwan Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with hepatocellular carcinoma caused by hepatitis B or C who will be treated by TACE Exclusion Criteria: * Previously treated by antiviral drugs for hepatitis B or C

Study Objectives This phase II trial is studying how well romidepsin works in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy, such as romidepsin, work in different ways to stop tumor cells from dividing so they stop growing or die. Conditions: Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Promyelocytic Leukemia (M3), Recurrent Adult Acute Myeloid Leukemia Intervention / Treatment: DRUG: romidepsin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed acute myeloid leukemia (AML) defined by the WHO classification * Initial diagnosis with either of the following: * Bone marrow or peripheral blood myeloblasts of at least 20%, * Recurring genetic abnormalities (e.g., t\[8;21\], inv 16, or t\[16;16\]) and * Bone marrow blast percentage less than 20% * Relapsed or refractory disease defined by 1 of the following: * Under 60 years of age and in second relapse or greater, * Over 60 years of age and in first relapse, * Acute promyelocytic leukemia that has relapsed despite prior tretinoin and arsenic therapy, * Primary refractory AML for which no standard therapy exists * Patients who are over 60 years of age with previously untreated disease and who refuse conventional chemotherapy are eligible * Patients who are over 60 years of age and in first relapse and poor medical candidates for reinduction chemotherapy or who refuse conventional chemotherapy are eligible * Not medically appropriate for OR refused curative bone marrow or stem cell transplantation * No CNS leukemia * ECOG 0-2 OR Karnofsky 60-100% * LVEF at least 40% by MUGA * QTc interval less than 500 msec by EKG * No myocardial infarction within the past 3 months * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior allergic reactions attributed to compounds of similar chemical or biological composition to FR901228 (depsipeptide) * No concurrent uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance * No ongoing or active infection * At least 4 weeks since prior autologous stem cell or bone marrow transplantation * No prior allogeneic stem cell or bone marrow transplantation * No concurrent biologic agents * At least 2 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) * No concurrent chemotherapy, concurrent hydroxyurea allowed during the first course of study therapy to control hyperleukocytosis * No concurrent radiotherapy * Recovered from prior therapy * At least 4 weeks since prior investigational agents * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No concurrent drugs known to have histone deacetylase inhibitor activity (e.g., sodium valproate) * No other concurrent antineoplastic agents * No prior FR901228 (depsipeptide) * At least 2 weeks since prior radiotherapy

Study Objectives A Pilot Phase II Study The primary objective for this study is: * To explore the usefulness of \[F-18\]RGD-K5 PET/CT to predict efficacy or early response to Avastin® (the anti-angiogenesis drug) plus chemotherapy treatment before the full course of treatment is completed The secondary objectives for this study are: * To continue safety evaluation by collection of safety data from all patients * To gain experience with \[F-18\]RGD-K5 PET/CT in order to improve the study design and conduct of future studies Design: An open label, non-randomized, uncontrolled, single group assignment, pilot efficacy study Duration: Screening visit (3-4 hrs), pre-treatment imaging visit of \[F-18\]RGD-K5 PET/CT (\~ 3-4 hrs) and the standard \[F-18\]FDG PET/CT (\~ 3-4 hrs) or diagnostic CT, followed by two \[F-18\]RGD-K5 PET/CT scans, one after the second but before the third Avastin® treatment, and one after the fourth but before the fifth Avastin® treatment, and a follow up standard \[F-18\]FDG PET (\~ 3-4 hrs) or diagnostic CT. Procedures: Informed consent, collection of demographic information, medical history, blood labs, physical examination, vital signs, ECGs, three sets of \[F-18\]RGD-K5 dosing and imaging scans including pretreatment, early mid-treatment, and later mid-treatment, concomitant medication collection, adverse event monitoring, and assessment of tumor response to treatment Patients: Approximately forty (40) patients with non-squamous non-small cell lung cancer, metastatic breast cancer, metastatic colon or rectum cancer who will receive chemotherapy plus Avastin®. This allows for approximately 30 evaluable patients to complete this study at approximately four to eight sites internationally Conditions: Metastatic Breast Cancer, Metastatic Colon/Rectum Cancer, Non-squamous Non-small Cell Lung Cancer Intervention / Treatment: DRUG: [F-18]RGD-K5 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patient is >18 years and male or female of any race / ethnicity * Patient or patient's legally acceptable representative provides written informed consent and willing to comply with protocol requirements * Patient must be scheduled to receive chemotherapy treatment(s) plus Avastin® for their cancer care; treatment management will be made by the treating medical oncologists (According to the package insert for Avastin®, it is administered as an IV infusion every 3 weeks for nonsquamous non-small cell lung cancer, and every 2 weeks for metastatic breast cancer, colon or rectum cancer) * Patient will be scheduled to have a clinical \[F-18\]FDG-PET/CT or diagnostic CT pre-treatment after the fourth but before the fifth Avastin® treatment Exclusion Criteria: * Patient is not capable of complying with study procedures * Female patient is pregnant or nursing; exclude the possibility of pregnancy by one of the following: * Confirming in medical history that the patient is postmenopausal for a minimum of one year, or surgically sterile * Confirming the patient is using one of the following methods of birth control for a minimum of one month prior to entry into this study: IUD, oral contraceptives, Depo-Provera, or Norplant * Confirming a negative urine dipstick test taken the morning of receiving the \[F-18\]RGD-K5 * Patient has a severe hepatic or renal disease as defined by previous medical history or abnormal renal and hepatic functions determined by lab results not within the following ranges, or in the opinion of the Investigator, the values are not acceptable for the patient to be included: * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limits of normal * Serum creatinine ≤ 2x institutional upper limits of normal * BUN within 2x institutional upper limits of normal * Patient has known hyper or hypo-coagulation syndromes. (e.g. Protein C, S deficiency, Hemophilia A/B/C, Factor-V Leiden, etc) or lab results are not within the following ranges, or in the opinion of the Investigator, the values are not acceptable for the patient to be included: Platelet counts of < 75 x 103/μL * Patient has known sensitivity to any components of Avastin® such as recombinant human or humanized antibodies * Patient has been involved in an investigative, radioactive research procedure within 7 days and during the study participation period * Patient will participate in experimental therapy procedures while participating in this clinical trial * Patient has any other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete data or data quality to achieve study objectives, or complete study and/or post-dose follow-up examinations

Study Objectives Colorectal cancer is the second leading cause of cancer-related death within the United States. Animal models and observational studies have suggested that marine-derived n-3 polyunsaturated fatty acids \[PUFA\] such as eicosapentanoic acid \[EPA\] and docosahexanoic acid \[DHA\] may reduce the risk of colorectal cancer. In addition, it may be the relative proportion of n-3 to n-6 PUFAs that best determines the chemopreventive effects of fish oils. This ratio is important because the n-6 PUFA, arachidonic acid (ARA), is converted via the cyclo-oxygenase (COX) pathway to prostaglandin E2 (PGE2), an inflammatory eicosanoid overproduced in colorectal neoplasms while EPA is converted to the anti-inflammatory prostaglandin E3 (PGE3). While the ratio of n-6 to n-3 PUFAs can be altered through dietary changes, genetic factors may also influence this ratio. Recent genetic studies have demonstrated that much of the tissue levels of ARA is determined by differences in a gene called fatty acid desaturase 1 (FADS1). FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA. The study hypothesis is that individuals with genetically determined lower activity of FADS1 will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity because of lower tissue levels of ARA and subsequently a more favorable n-6 to n-3 PUFA ratio. To test this hypothesis the investigators will recruit 150 participants with recently identified adenomatous polyps and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. The first factor will be FADS1 genotype (GG, GT, and TT) and the second factor will be fish oil supplementation (fish oil versus placebo). The primary outcome will be the change in rectal epithelial cell growth and cell death. Secondary outcomes will include rectal epithelial cell expression of genes important in PGE2 production, rectal cell production of PGE2 and PGE3, rectal mucosal tissue levels of fatty acids, and changes in biomarkers of inflammation (C-reactive protein), adipokines (leptin, adiponectin), and markers of insulin sensitivity. The specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention. The investigators long-term objectives are to determine genetic factors that might influence the efficacy of fish oil supplementation in order to conduct a more definitive adenoma recurrence trial using marine-derived n-3 PUFAs. The investigators anticipate that fish oil will have anti-neoplastic effect and individuals with low FADS1 activity will have a greater response compared to individuals with high FADS1 activity Conditions: Colorectal Adenomatous Polyps Intervention / Treatment: DRUG: Eicosapentanoic acid and docosahexanoic acid, DRUG: Oleic Acid Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: FACTORIAL Masking: QUADRUPLE

Inclusion Criteria: * ≥ 40 and < 80 years of age * History of 1 or more adenomatous polyps * Consent to be contacted for future studies * Participants with known genotype for rs174535 in FADS1 * Prior participation in the Tennessee Colorectal Polyp Study or the Personalized Prevention of Colorectal Cancer Trial Exclusion Criteria: * Previously resected colorectal cancer * Coronary artery disease or congestive heart failure * Current metabolic or life-threatening disease * Currently taking fish oil supplements * Inability or unwillingness to stop NSAIDs or ASA during the study * Allergic to fish products * Diagnosis of inflammatory bowel disease * Diagnosis of any cancer (except non-melanoma skin cancer) * Diagnosis of liver or kidney disease * Pregnant or breast feeding

Study Objectives This study will assess the efficacy and safety of intravenous Avastin in combination with chemotherapy regimens as second-line treatment of metastatic cancer of the colon or rectum. The anticipated time of study treatment is until disease progression. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: bevacizumab [Avastin] Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with metastatic colon or rectal cancer, progressing or relapsing after first-line treatment; * Women of childbearing potential must use adequate contraception up to at least 6 months after the last dose of bevacizumab. Exclusion Criteria: * Patients with metastatic colon or rectal cancer scheduled for a first-line systemic treatment; * Untreated brain metastases, spinal cord compression or primary brain tumours; * Pregnant or lactating women; * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study start; * Treatment with any investigational drug, or participation in another investigational study, within 30 days prior to enrollment.

Study Objectives This phase 0 trial studies ixazomib citrate in treating patients with glioblastoma that has spread or returned after period of improvement who are planning to undergo surgery. When given by mouth, ixazomib may be able to reach tumor cells in the brain. Studying samples of tissue, blood, and plasma in the laboratory from patients receiving ixazomib may help doctors learn more about the effects of ixazomib on the cells. It may also help doctors understand how well patients will respond to treatment. Conditions: Glioblastoma Intervention / Treatment: DRUG: Ixazomib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care * Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) * Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) * Patients must have a previous diagnosis of a recurrent or progressive glioblastoma for which surgical resection is now indicated * Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2 or (Karnofsky performance status of 60 or above) * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³; platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment * Hemoglobin > 9 g/dL * Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN for the lab utilized * Creatinine ≤ 1.5 mg/dL * Calculated creatinine clearance ≥ 30 mL/min Exclusion Criteria: * Female patients who are lactating or have a positive serum pregnancy test during the screening period * Failure to have fully recovered (ie, ≤ grade 1 toxicity) from the reversible effects of prior chemotherapy * Major surgery, including craniotomy, within 14 days before enrollment * Radiotherapy of brain tumor within 3 months before enrollment * Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment * Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months * Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of ginkgo biloba or St. John's wort * Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol * Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent * Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing * Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection * Patient has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period * Participation in other clinical trials utilizing other therapeutic investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial * Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not

Study Objectives The primary objective of the study is to study the pharmacokinetics of pyrotinib and docetaxel plus Trastuzumab in HER2 Positive MBC. The secondary objective of the study is to evaluate the safety and efficacy (ORR) of pyrotinib and docetaxel plus Trastuzumab in HER2 Positive MBC. Conditions: Metastatic Breast Cancer Intervention / Treatment: DRUG: Docetaxel, trastuzumab, DRUG: Pyrotinib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * HER2 positive recurrent or metastasis breast cancer. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Adequate organ function. * Signed, written inform consent obtained prior to any study procedure. Exclusion Criteria: * Patients received more than 1 line of chemotherapy or immunotherapy in the phase of recurrence / metastasis. * History of HER tyrosine kinase inhibitors or monoclonal antibody for breast cancer in any treatment setting，except trastuzumab ,or Pertuzumab used in the neo-adjuvant or adjuvant setting. * Assessed by the investigator to be unable receive systemic chemotherapy. * History of other malignancy within the last 5 years，except for carcinoma in situ of cervix，basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. * Pregnant or lactating women，or for women of childbearing potential unwilling to use a highly-effective contraception during of the study treatment and for at least 7 months after the last dose of study treatment.

Study Objectives This is an open label, single arm phase II study, to determine the overall response rate for the combination of lenvatinib and pemrolizumab in patients with metastatic gastroesophageal cancer who have progressed on first or subsequent line therapies. Given the significant cross talk between angiogenesis and the immune response, combined therapy with lenvatinib and pemrolizumab in advanced gastroesophageal cancer patient will provide improved outcomes compared to standard treatment with currently approved agents. Conditions: GastroEsophageal Cancer, Gastric Cancer Intervention / Treatment: DRUG: Lenvatinib, DRUG: Pembrolizumab 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: * Be willing and able to provide written informed consent/assent for the trial. * Be greater than 18 years of age on day of signing informed consent. * Have histologically or cytologically confirmed metastatic or recurrent gastric or GEJ adenocarcinoma. * Have measurable disease based on RECIST 1.1. * Must have received and have progressed, or are intolerant to at least one systemic regimen (platinum- or fluoropyrimidine-based chemotherapy regimen for metastatic or recurrent disease.) * If Her2 positive, must have received and have progressed or are intolerant to treatment with trastuzumab for metastatic or recurrent disease. * Subjects must consent to provide archival tumor tissue (initial and subsequent tumor biopsy samples, if possible) for correlative biomarker studies. * Have a performance status of 0 or 1 on the ECOG Performance Scale. * Adequately controlled blood pressure with or without antihypertensive medications defined as BP < 140/90 mmHg at screening and no change in antihypertensive mediation within 1 week prior to the Screening Visit. * Demonstrate adequate organ function as defined in Table 5, all screening labs should be performed within 10 days of treatment initiation. * Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential (Section 5.5.2) must be willing to use an adequate method of contraception as outlined in Section 5.5.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. * Male subjects of childbearing potential (Section 5.5.2) must agree to use an adequate method of contraception as outlined in Section 5.5.2 - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. * Has a known history of active TB (Bacillus Tuberculosis) * Hypersensitivity to pembrolizumab or lenvatinib or any of its excipients. * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. * Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. * Note: If subject received major surgery, a minimum of four weeks must have passed and they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Subjects having >1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein >1g/24h will be ineligible. * Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib. * Prolongation of QTcF interval to >480ms * Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug. * Bleeding disorders or active significant bleeding (i.e. hemoptysis, hematochezia, hematemesis) within 3 weeks. * Thrombotic disorders or use of anticoagulants, such as warfarin, requiring therapeutic international normalized ratio (INR) monitoring. (treatment with low molecular weight heparin (LMWH) or direct acting oral anti-coagulants is allowed.) * History of prior gastrointestinal fistula and/or perforation. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. * Has known history of, or any evidence of active, non-infectious pneumonitis. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days of planned start of study therapy. * Arrhythmias requiring Class Ia and III antiarrhythmics and/or grade >2 bradycardia.

Study Objectives Primary Objective: To determine the dose limiting toxicity (DLT), the maximum administered dose (MAD) and the maximum tolerated dose (MTD) of AVE8062 and docetaxel in combination administered sequentially on D1 \& D2 respectively every 3 weeks in patients with advanced solid tumors. Secondary Objectives: * To define the overall safety profile of the combination. * To characterize the pharmacokinetic (PK) profile of AVE8062 and docetaxel when administered in combination. * To evaluate anti-tumor activity of the combination. * To evaluate potential predictive biomarkers. The study includes a tumoral pharmacogenomic sub-study conducted in a subset of sites. The objective to analyse a set of biological biomarkers in order to identify a potential predictive signature of efficacy for AVE8062 in combination with docetaxel. Conditions: Advanced Neoplastic Disease Intervention / Treatment: DRUG: AVE8062, DRUG: Docetaxel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Advanced neoplastic disease (i.e metastatic or locally advanced disease) for which docetaxel-based regimen therapy is indicated such as breast, non-small cell lung and prostate cancer. * ECOG performance status of 0 to 1. Exclusion criteria: * Concurrent treatment with any other anticancer therapy. * Patient with locally advanced or metastatic breast cancer who never received adjuvant chemotherapy. * Brain metastases and carcinomatous leptomeningitis. * Prior intensive chemotherapy with autologous stem cell rescue. * Patients who received a high cumulative dose of anthracycline (i.e doxorubicin > 400mg/m2 or epirubicin >750 mg/m2). * Impaired cardiovascular function. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Objectives The purpose of this study: To explore the comparative effectiveness of BIBF 1120 in terms of : * Progression-free survival (PFS), objective response, overall survival * Evaluate and compare safety Conditions: Colorectal Cancer Intervention / Treatment: DRUG: mFOLFOX6 + BIBF 1120, DRUG: mFOLFOX6+placebo Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically proven colorectal adenocarcinoma * Intended treatment with mFOLFOX6 after one prior palliative chemotherapy for metastatic CRC * Age > 18 years * Metastatic disease not suitable for curative-intent surgery * Measurable (> 1 cm) and evaluable disease (according to RECIST 1.1 criteria) * Prior bevacizumab, cetuximab or panitumumab are allowed. * Previous adjuvant oxaliplatin-containing therapy is allowed, if the end of adjuvant chemotherapy is >12 months prior to inclusion into the trial * ECOG performance status 0 or 1 (see appendix 10.4) * Adequate hepatic function * Adequate Renal function * Adequate bone marrow function * Other lab parameters: proteinuria < CTCAE grade 2, Prothrombin time and/or partial thromboplastin time < 50 % deviation from normal limits * Life expectancy at least 3 months * Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation Exclusion Criteria: * Known hypersensitivity to the trial drugs or their excipients. * Treatment with any investigational drug within 28 days of trial onset. * Prior treatment with more than one line of palliative standard chemotherapy for colorectal cancer, prior treatment with a tyrosine kinase inhibitor, prior palliative treatment with an oxaliplatin-containing regime. * History of other malignancies in the last 5 years, in particular those which could affect compliance with the protocol or interpretation of results. Patients with adequately treated basal or squamous cell skin cancer are generally eligible. * Serious concomitant disease, especially those that would limit compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial. * Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period. Portimplantation prior to therapy is allowed. * Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure > NYHA II) (see appendix 10.3). * History of severe haemorrhagic or thrombotic events in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). Known inherited predisposition to bleeds or to thrombosis. * Patient with brain metastases that are symptomatic and/or require therapy. * Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid ≤ 325mg per day) * History of major thrombotic or clinically relevant major bleeding event in the past 6 months * Current peripheral neuropathy ≥ CTCAE grade 2 except due to trauma * Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy * Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug * Active alcohol or drug abuse. * Women and men who are sexually active and unwilling to use a medically acceptable method of contraception * Pregnancy or breast-feeding * Leptomeningeal disease * Radiographic evidence of cavitary or necrotic tumours * Centrally located tumours with radiographic evidence (CT or MRI) of local invasion of major blood vessels * Severe chemotherapy-associated toxicity during or after adjuvant or palliative first-line chemotherapy like 5-FU-associated cardiac toxicity (coronary spasm) or persistent oxaliplatin-associated peripheral neuropathy (≥ CTCAE grade 2) with paresthesia associated with pain or functional impairment (after adjuvant oxaliplatin-containing chemotherapy).

Study Objectives This open-label, multi-center, dose-escalation study will evaluate the safety, pharmacokinetics, and therapeutic activity of RO6895882 in participants with Carcinoembryonic Antigen (CEA)-positive solid tumors who have progressed on the standard of care therapy. The study will be conducted in 3 parts. Part 1 will be a single ascending dose study in single participant cohort at low RO6895882 dose (less than or equal to \[\</=\] 6 milligrams \[mg\]). Part 2 will be a dose-escalation study of RO6895882 monotherapy given every week (qw), every 2 weeks (q2w), and possibly every 3 weeks (q3w). Part 3 will be an expansion phase of the qw, q2w, and possibly q3w at maximum tolerated dose (MTD) (as determined in Part 2). Part 3 will only be conducted if the risk/benefit assessment, as evaluated by the Sponsor and the investigators, is in favor of the participants. Participants will be treated until disease progression, unacceptable toxicity or withdrawal from treatment for other reasons or death for a maximum duration of 24 months. Conditions: Neoplasms Intervention / Treatment: DRUG: RO6895882 Location: Finland, Netherlands, Spain, Switzerland, United Kingdom, Denmark, United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participants with confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of non-critical location accessible to biopsy who have progressed on the standard of care therapy * Locally confirmed CEA expression in tumor tissue (more than \[>\] 20 percent (%) of tumor cells staining with at least moderate intensity) or centrally confirmed CEA expression if no archival tumor tissue and fresh biopsy is collected * Radiologically measurable and clinically evaluable disease * Life expectancy of greater than or equal to (>=) 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 * All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade <=1, except alopecia (any grade) and Grade 2 peripheral neuropathy * Adequate hematological, liver, and renal function * Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women <=2 years after menopause * Participants with Gilbert's syndrome will be eligible for the study. A diagnosis of Gilbert's syndrome will be based on the exclusion of other diseases based on the following criteria: (i) unconjugated hyperbilirubinemia noted on several occasions; (ii) no evidence of hemolysis (normal hemoglobin, reticulocyte count, and Lactate dehydrogenase); (iii) normal liver function tests; (iv) absence of other diseases associated with unconjugated hyperbilirubinemia Exclusion Criteria: * History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before screening * Participants with an active second malignancy (other than non-melanoma skin cancer, or cervical carcinoma in situ). Participants who have a history of malignancy are not considered to have an active malignancy if they have completed therapy and are considered by their treating physician to be at less than (<) 30% risk for relapse * Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases * Uncontrolled hypertension (systolic >150 millimeter of mercury \[mmHg\] and/or diastolic >100 mmHg), unstable angina, congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment * Active or uncontrolled infections * Known infection with human immunodeficiency virus (HIV), seropositive status * Positive test results for chronic hepatitis B infection (defined as positive Hepatitis B surface antigen \[HBsAg\] serology and/or HBcAb status) * Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing) * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug * Pregnant or breast-feeding women * Known hypersensitivity to any of the components of RO6895882 * Concurrent therapy with any other investigational drug * Regular immunosuppressive therapy (that is, for organ transplantation, chronic rheumatologic disease) * Chronic use of steroids (including inhaled) will not be allowed. Concurrent high doses of systemic corticosteroids. High dose is considered as >20 mg of dexamethasone a day (or equivalent) for >7 consecutive days * Radiotherapy within the last 4 weeks before start of study drug treatment with the exception of limited field palliative radiotherapy for bone pain relief

Study Objectives RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation therapy regimens to see how they work in treating patients with stage II or stage III bladder cancer that was removed by surgery. Conditions: Bladder Cancer Intervention / Treatment: DRUG: induction cisplatin, DRUG: induction 5-fluorouracil, DRUG: induction gemcitabine, RADIATION: Induction BID radiation therapy, RADIATION: Induction QD radiation therapy, RADIATION: Consolidation BID radiation therapy, RADIATION: Consolidation QD radiation therapy, DRUG: consolidation gemcitabine, DRUG: consolidation 5-fluorouracil, DRUG: consolidation cisplatin, PROCEDURE: radical cystectomy, PROCEDURE: Post-Induction Chemoradiotherapy Endoscopic Response Evaluation, DRUG: adjuvant gemcitabine, DRUG: adjuvant cisplatin Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion criteria: * Pathologically (histologically or cytologically) proven diagnosis of primary carcinoma of the bladder (transitional cell cancer) within 8 weeks of registration. Operable patients whose tumors are primary carcinomas of the bladder and exhibit histologic evidence of muscularis propria invasion and are American Joint Committee on Cancer (AJCC) clinical stages T2-T4a, Nx or N0, M0 (Appendix IV) without hydronephrosis; patients who have involvement of the prostatic urethra with transitional cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible. T2a, T2b, T3a, T3b -substages‖ are not usually able to be determined with clinical (TURBT) staging. * If radiologic evaluation of a lymph node is interpreted as "positive", this must be evaluated further either by lymphadenectomy or percutaneous needle biopsy. Patients with histologically or cytologically confirmed node metastases will not be eligible. * Patients must have an adequately functioning bladder after thorough evaluation by an urologist and have undergone as thorough a transurethral resection of the bladder tumor as is judged safely possible. * Patients must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy by the joint agreement of the participating Urologist, Radiation Oncologist, and Medical Oncologist. * History and physical examination including weight, performance status, and body surface area within 8 weeks prior to study registration * Zubrod Performance Status ≤ 1 * Age ≥ 18 * Complete blood count (CBC)/differential obtained no more than 4 weeks prior to registration on study, with adequate bone marrow function defined as follows: * 8.1 White blood cell count (WBC) ≥ 4000/ml * 8.2 Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3; * 8.3 Platelets ≥ 100,000 cells/mm3; * 8.4 Hemoglobin (hgb) ≥ 10.0 mg/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.); * Serum creatinine of 1.5 mg% or less; serum bilirubin of 2.0 mg% or less; creatinine clearance of 60 ml/min or greater no more than 4 weeks prior to registration; Note: Calculated creatinine clearance is permissible. If the creatinine clearance is > 60 ml/min, then a serum creatinine of up to 1.8 mg% is allowable at the discretion of the study chair; * Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior to study entry; women of childbearing potential and male participants must practice adequate contraception. * Patient must be able to provide study-specific informed consent prior to study entry. Exclusion criteria: * Evidence of tumor-related hydronephrosis * Evidence of distant metastases or histologically or cytologically proven lymph node metastases * Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy * A prior or concurrent malignancy of any other site or histology unless the patient has been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix * Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease * Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside) * Severe, active co-morbidity, defined as follows: * 7.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; * 7.2 Transmural myocardial infarction within the last 6 months; * 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; * 7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; * 7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol. * 7.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients. * Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. * Prior allergic reaction to the study drug(s) involved in this protocol

Study Objectives This is a randomized controlled trial (RCT) to evaluate the influence of different doses of vitamin D3 (800 IU/d versus 400 IU/d), on serum levels of interleukin (IL)-6, TNF-alpha and C- reactive (CRP) in premature infants with clinical evidence of late-onset sepsis and to assess its influence on clinical outcomes of these infants. Conditions: Prematurity, Late-onset Sepsis Intervention / Treatment: DRUG: High-dose vitamin D 3, DRUG: Conventional-Dose Vitamin D 3 Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Preterm Infants (28-37 wk gestational age) * Late-onset sepsis defined as clinical signs suggestive of infection after 72 h of birth. Clinical sepsis will be defined as the presence of three or more of the following categories of clinical signs: 1. Temperature instability (hypothermia, hyperthermia); 2. Respiratory (grunting, intercoastal retraction, apnea, tachypnea, cyanosis); 3. Neurologic (hypotonia, lethargy, seizures); 4. Gastrointestinal (feeding intolerance, abdominal distension). Exclusion Criteria: * Major congenital anomalies. * Chromosomal anomalies. * Known inborn error(s) of metabolism

Study Objectives This study is for patients who have been diagnosed with soft tissue sarcoma that has spread (metastasized) or that is not eligible for removal by surgery. The purpose of this study is to determine how soft tissue sarcomas respond to treatment with an investigational drug called tivozanib. In some lab and clinical studies, tivozanib has been shown to interfere with the growth of some types of tumors. The study will also evaluate how safe the study treatment is by observing how many and what kind of adverse events (side effects) participants experience. Conditions: Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma Intervention / Treatment: DRUG: tivozanib, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have histologically or cytologically confirmed sarcoma of soft tissue * Patients must have metastatic and/or locally advanced or locally recurrent disease * Patients must have measurable disease within 4 weeks prior to registration by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; tumor lesions that are situated in a previously irradiated area may be considered measurable for the purposes of this study only if there is evidence of growth of the area following a course of irradiation that cannot be attributed to necrosis or bleeding into the tumor * Patients must have had a minimum of 1 and a maximum of 4 prior chemotherapy regimens for recurrent/metastatic disease (it will be up to the treating investigator to define what constitutes a "regimen" in each case); the last dose of systemic therapy (include tyrosine kinase inhibitors) must have been given at least 4 weeks prior to initiation of therapy; patients receiving BCNU or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy * Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids are eligible for study * Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Absolute neutrophil count >= 1.5 x 10\^9/l * Platelets >= 75 x 10\^9/l * Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known Gilbert Syndrome) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 2.5 x institutional ULN * Serum creatinine =< 1.5 x ULN * If urine protein:creatinine (UPC) >= 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < 1g to be eligible * Patients must not have current evidence of another malignancy; there are no restrictions regarding prior history of malignancy * If female and of childbearing potential, documentation of negative pregnancy test is required within 7 days prior to first dose; sexually active males and females of childbearing potential must agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug; all subjects (and their partners) must agree to use a highly effective method of contraception; effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods; effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm) * Note: oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study * Adverse events related to prior tumor-specific therapy must have resolved to less than or equal to National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) (version 4) grade 1 prior to study entry (except alopecia) * Patients taking cytochrome P450 (CYP)3A4 inducers at the time of screening/registration are still eligible for participation, but whenever possible these medications should be discontinued or changed to one that is not an inducer * NOTE: No washout period is required * NOTE: It will be up to the treating investigator's discretion to assess whether or not the risk of discontinuing or changing the medication is higher or lower than the risk of continuing it while on study for the individual patient * Patients must have the ability to understand and the willingness to sign a written informed consent document; signed and dated informed consent must be obtained prior to registration on trial Exclusion Criteria: * Patients with any one of the following sarcoma histological subtypes will not be eligible for participation: alveolar soft-part sarcoma, chondrosarcoma, dermatofibrosarcoma, Ewing sarcoma, gastrointestinal stromal tumor (GIST), Kaposi sarcoma, mixed mesodermal tumor/carcinosarcoma, osteosarcoma, and low grade (grade 1) sarcomas; NOTE: Myxoid liposarcoma with t(12;16) or t(22;22) is permitted; rhabdomyosarcoma (Embryonal, Alveolar, pleomorphic), interdigitating dendritic sarcoma, giant cell tumor of bone * Patients who have had major surgery within 21 days or those who have not recovered from adverse events associated with surgery to =< grade 1 will not be eligible for participation; excluded from such considerations are surgical changes not expected to improve, e.g. removal of muscle tissue; patients may be on replacement glucocorticoids for pre-existing glucocorticoid deficiency (e.g. Addison's disease) * Patients receiving any other investigational agents will not be eligible for participation * Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib will not be eligible for participation * Patients with serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with safety, provision of informed consent, or compliance to study procedures and requirements will not be eligible for participation, including but not limited to: * Uncontrolled intercurrent illness * Ongoing or active infection including HIV, active hepatitis B or C) * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements will not be eligible for participation * Pregnant women and women who are breast-feeding will not be eligible for participation * Patients with a history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis will not be eligible for participation; NOTE: Individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 3 months prior to first dose of study drug are the exception; screening with CNS imaging studies such as CT or magnetic resonance imaging (MRI) is required only if clinically indicated or if the subject has a history of CNS metastases * Patients with clinically significant gastrointestinal (GI) abnormalities that may increase the risk for GI bleeding will not be eligible for participation; these include, but are not limited to: * Active peptic ulcer disease * Known intraluminal metastatic lesion/s with risk of bleeding * Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other GI conditions with increased risk of perforation * History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment * Clinically significant (> 1/2 teaspoon) hemoptysis or gastrointestinal hemorrhage in the past 6 months * Patients with evidence of active bleeding or bleeding diathesis will not be eligible for participation; recent hemoptysis would be >= 1/2 teaspoon of red blood within 8 weeks before first dose of study drug * Patients with clinically significant GI abnormalities that may affect absorption of investigational product will not be eligible for participation; these include but are not limited to: * Malabsorption syndrome * Major resection of the stomach or small bowel * Patients with a corrected QT interval (QTc) > 480 msecs using Bazett's formula (QT Interval / square root(RR interval)) will not be eligible for participation * Patients with left ventricular ejection fraction (LVEF) < 50% will not be eligible for participation * NOTE: patients who do not meet the cutoff for LVEF may be re-screened at a later date and, if eligible then, may be enrolled in the study * Patients with a history of any one or more of the following cardiovascular conditions within the past 6 months will not be eligible for participation: * 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) * Patients with poorly controlled hypertension \[defined as systolic blood pressure (SBP) of >= 140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg\] will not be eligible for participation * Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals; at least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement; these three values will be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure; the mean SBP / DBP ratio must be < 140/90 mmHg in order for a subject to be eligible for the study * Patients with cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months will not be eligible for participation * Note: subjects with recent DVT who have been therapeutically coagulated for at least 6 weeks are eligible * Patients who had major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery) will not be eligible for participation * Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels will not be eligible for participation * Note: tumor abutting the vessel is acceptable, but contiguous tumor and vessel is not; CT with contrast is strongly recommended to evaluate such lesions

Study Objectives Primary Objective: 1. To determine whether the use of a fibrin sealant applied to superficial groin soft tissues following node dissection can result in decreased cumulative postoperative drainage, earlier drain removal, and lower incidence of seroma. Secondary Objectives: 1. To determine the postoperative morbidity rate using fibrin sealant following superficial groin dissection. 2. To assess patient-valuation of outcome by performing a cost-benefit analysis using a willingness-to-pay model. 3. To determine if serum levels, lymphatic fluids level, or cutaneous expression of vascular endothelial growth factor-D (VEGF-D), vascular endothelial growth factor-C (VEGF-C) or their receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) correlates with nodal tumor burden or development of lymphedema in patients with melanoma. Conditions: Melanoma Intervention / Treatment: DRUG: Fibrin Sealant Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Part I - Inclusion Criteria Patients that consent to participate. * Patients with melanoma who have undergone superficial node dissection (with or without a concurrent deep (ilioinguinal) node dissection within the last six months as part of their surgical treatment will be considered for the study. * Part II- Inclusion Criteria Patients that consent to participate. * Patients with melanoma for which a superficial node dissection is indicated (with or without a concurrent deep (ilioinguinal) node dissection. Exclusion Criteria: * Part II - Exclusion Criteria Patients with known hypersensitivity to bovine proteins. * Patient has undergone prior radiation therapy to the operative site (groin). * Patient is pregnant or lactating. * Patient is steroid dependent within last 6 months. * Patient has used aspirin or other anti-platelet drug (excluding Celebrex) within seven days of operation. * Patients with pre-existing lymphedema. * Patients with other pre-existing medical conditions as per the discretion of the principal investigator.

Study Objectives This is a Phase 1, First-in-Human, Multicentre, Open-label Study of RC118 for Injection in Patients with Locally Advanced Unresectable/Metastatic Solid Tumours to determine the safety and tolerability of RC118, including the maximum tolerated dose (MTD)/maximum administered dose (MAD), and to define the recommended Phase II dose (RP2D). Conditions: Unresectable Solid Tumor, Metastatic Solid Tumor, Locally Advanced Solid Tumor Intervention / Treatment: DRUG: RC118 for injection Location: Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must be able to provide documented voluntary informed consent. * Male or female patient ≥ 18 years and ≤ 75 years. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0 or 1. * The expected survival period exceeds 12 weeks. * At least one target lesion that can be measured per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. * Histologically documented, incurable, unresectable locally advanced or metastatic tumours that are intolerable or refractory to standard therapies. * Patients agree to provide pre-treatment archived /biopsy tumour samples for retrospective Claudin 18.2 test. Archival tumour tissue should be from the most recent timepoint before entering the trial. In addition, archived samples obtained out of the screening are acceptable if it is discussed and approved by the Investigator and Sponsor in advance. Only when archived samples cannot be obtained, the biopsy will be considered at screening. Fresh tumour biopsies will NOT be considered if significant risk procedures are required with the discretion of Investigator. * Adequate bone marrow, liver, and renal function defined as: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 100 × 109/L, haemoglobin ≥ 90 g/L, serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), ALT, AST or ALP ≤ 2.5 × ULN (≤ 5 × ULN when there is known liver metastasis), serum creatinine ≤ 1.5 × ULN, INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN. * Willingness to avoid pregnancy or fathering children based on the criteria below: * Female patients of childbearing potential and male patients with partners of childbearing potential treated with RC118, must agree to use a highly effective form(s) of contraception during study and within 6 months after the last dose. Those methods include but not limited to combined (oestrogen and progestogen containing) hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence. * Females of non-childbearing potential (e.g., surgically sterile with a hysterectomy and/or bilateral oophorectomy or chemically sterile or ≥ 12 months of amenorrhea in the absence of chemotherapy, anti-oestrogens, or ovarian suppression). Those females do not need to undergo pregnancy test. Exclusion Criteria: * Women who are pregnant or breastfeeding. * Diagnosed active hepatitis B infection (defined as positive of hepatitis B surface Ag and hepatitis B DNA≥500IU/ml), active hepatitis C infection (defined as presence of hepatitis C RNA), and human immunodeficiency virus infection (defined as positive HIV test) during the screening period. * Received vaccines within 4 weeks prior to administration or plan on receiving any vaccine during the study. * Subjects with a history of other acquired/congenital immunodeficiency diseases or organ transplantation. * Patients have history of targeted therapy of Claudins, or participated in other clinical trials and received investigational product within 4 weeks before the first administration of study drug. * Allergic constitution or allergic to known research drug active ingredients or excipient. * Patients who are under the treatment of anticoagulant drugs (e.g., warfarin, apixaban, and heparin). Patients using prophylactic doses of heparin (e.g., LMWH) is eligible in the study. * Patients undergoing any anti-tumour therapy, including surgery, chemotherapy, radiotherapy and biological therapy, within 4 weeks prior to the first administration of study drug, or palliative radiotherapy for bone/other solitary metastases within 2 weeks prior to the first administration of study drug. * Previous adverse reactions resulting from previous anti-tumour therapies, which have not returned to Grade 0 or 1 according to NCI-CTCAE v5.0 (except alopecia) at screening. * There are clinical symptoms of fluid in the third space (e.g., large amounts of pleural fluid or ascites) that cannot be controlled by drainage or other therapies. * A clinically significant active infection judged by the investigator. * Comorbidities that may seriously endanger the patient's safety or affect the completion of the study, such as gastrointestinal bleeding (within 4 weeks prior to the screening period), peptic ulcer, intestinal obstruction, intestinal paralysis, interstitial pneumonia, pulmonary fibrosis, kidney failure, and uncontrolled diabetes. * QTc interval > 480 ms in both male and female (based on the mean value of the triplicate screening ECGs); family or personal history of long/short QT syndrome, History of ventricular arrhythmia deemed clinically significant by the investigator, or currently receiving antiarrhythmic drug treatment, or implantation of arrhythmia defibrillation device. * History of myocardial infarction within 6 months prior to the screening period, severe or unstable angina pectoris, coronary or peripheral artery bypass grafting, heart failure ≥ 3 (New York Heart Association), or uncontrolled hypertension. * Patients with known current alcohol dependence or drug abuse. * Patients with a long-term history of systemic steroid therapy. Patients with short-term (≤ 7 days) use and drug withdrawal > 2 weeks are eligible. * History or presence of uncontrolled primary brain tumours (e.g., leptomeningeal carcinomatosis) or metastatic brain tumours, unless considered stable by the Investigator and local therapy was completed. * History or presence of Grade ≥ 2 peripheral neuropathy. * History or presence of uncontrolled mental illness at the discretion of the Investigator, which may place the participant at increased risk of safety/tolerability issues. * The patient is, in the opinion of the investigator, expected to be non-compliant with critical trial procedures and is not willing or able to adhere to the trial requirements in the future. * Patients who are not appropriate for this clinical trial at the discretion of the investigator.

Study Objectives The primary purpose of this study is to help answer the following research question: whether enzastaurin given together with fulvestrant can help participants who have breast cancer and make the tumor smaller or disappear and for how long. Conditions: Breast Cancer Intervention / Treatment: DRUG: enzastaurin, DRUG: placebo, DRUG: fulvestrant Location: Germany, Netherlands, Italy, Spain, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Female participants with a histological-documented diagnosis of locally advanced or metastatic breast cancer. The primary or metastatic tumor must be estrogen response (ER) and/or parathyroid hormone receptor (PtR) positive. Note: Hormone receptor positivity is defined as ER or PtR greater than 10 fmol/mg by biochemical assay or 10% positive cells by immunohistochemistry * Participants are resistant to aromatase inhibitors (AI) therapy * Females with postmenopausal status * Previous radiation therapy is allowed, but should have been limited * Measurable or non-measurable disease * Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale * Have adequate organ function * Have an estimated life expectancy of at least 24 weeks * Must sign an informed consent document Exclusion Criteria: * Have had prior treatment with fulvestrant or enzastaurin * Are receiving concurrent administration of any other antitumor therapy, with the exception of gonadotropin-releasing hormone (GnRH) antagonists. * Have received treatment within the last 4 weeks with a drug that has not received regulatory approval for any indication at the time of study entry * Have received supplemental estrogen or progesterone within 4 weeks prior to study entry * Are hormone estrogen receptor (HER2)-positive * Are unable to discontinue use of anticoagulants * Have hypercalcemia * Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment * Have documented central nervous system (CNS) metastases, symptomatic pulmonary lymphangitis, or involvement of more than 1/3 of the liver * Have a serious concomitant systemic disorder * Have a serious cardiac condition * Are unwilling or unable to discontinue use of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy * Are unable to swallow tablets.

Study Objectives The purpose of this study is to assess the 2-year progression-free survival rate. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Bortezomib, DRUG: Melphalan, DRUG: Prednisone Location: Korea, Republic of Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Participants who are naïve to chemotherapy for multiple myeloma and not eligible for autologous stem cell transplantation * Participants with symptomatic multiple myeloma: a) Intramedullary monoclonal plasma cells greater than or equal to (>=) 10% or histologically confirmed plasmacytoma; b) Presence of monoclonal protein in the serum or urine; c) Myeloma-related organ impairment as defined in protocol * Participants with presence of an illness that is detectable by definitions as defined in protocol * Postmenopausal, sterilized or sexually inactive women, including women of childbearing potential who exercise effective contraceptive measures before and during the clinical trial Exclusion Criteria: * Participants with previous experience of receiving a therapy for multiple myeloma (excluding radiotherapy and dexamethasone < 160mg in total) * Participants with severe peripheral neuropathy (Grade >= 2 by NCI CTC version 4.0) * Pregnant or breastfeeding mothers * Participants with mental illness that can interfere with his/her cooperation with the therapy or the monitoring conditions of the clinical trial * Participants with other serious medical conditions (such as uncontrolled hypertension, diabetes mellitus and active infections)

Study Objectives The purpose of this study is to evaluate the safety and effectiveness of bevacizumab plus erlotinib following radical prostatectomy. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Erlotinib + Bevacizumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Karnofsky performance status of > 80 * Patients must have localized, organ-confined prostate cancer documented by physical examination, CT scan, or bone scan, and must have undergone radical prostatectomy. Post RP must have documented node negative prostate cancer. * Pretreatment granulocyte count > 1500/mm3, hemoglobin > 9.0 g/dL, and platelet count > 100,000/mm3, * Normal PT and PTT * Serum creatinine < 2.0 mg/dL * Adequate hepatic function with a serum bilirubin < upper limit of normal (ULN), AST and ALT < 1.5x ULN, and alkaline phosphatase < 2.5x ULN. * High-risk prostate cancer defined as a pre-RP prostate specific antigen level > 15 ng/dL or a Gleason score of > 8 or Stage T3 disease or positive surgical margins * Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for 3 months thereafter Exclusion Criteria: * Evidence of small cell (neuroendocrine) tumor * Evidence of metastatic disease * Prior administration of immunotherapy, biological therapy, hormonal therapy or radiation therapy for prostate cancer * Active secondary malignancies (other than basal cell carcinoma of the skin) * Serious, nonhealing wound, ulcer, or bone fracture. * Clinically significant cardiovascular disease (e.g., blood pressure of >150/100 mmHg, myocardial infarction, or unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or clinically significant peripheral vascular disease. Patients with a history of myocardial infarction or stroke within the last 6 months will be excluded. * Presence of seizures not controlled with standard medical therapy * Active infection requiring parenteral antibiotics at the time of the first administration of study drugs * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0. * Current, recent (within the 4 weeks preceding Day 0), or planned participation in another experimental drug study * Inability to comply with the study visit and follow-up schedule or procedures * History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications. * Urine protein:creatinine ration > 1.0 at screening * Evidence of bleeding diathesis or coagulopathy. * History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days prior to Day 0. * Presence of central nervous system or brain metastases

Study Objectives The purpose of this study is to determine if this epothilone leads to a response in patients with recurrent ovarian cancer that has progressed during, or in the last six months since a treatment of platinum-based chemotherapy. We also aim to look at the safety of the study drug and assess the impact of the infusion duration on tolerability. Conditions: Ovarian Neoplasms Intervention / Treatment: DRUG: Sagopilone (BAY86-5302 , ZK219477) Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria:- Females aged 18 or over - Cancer of any of the following types: -- epithelial ovarian cancer -- peritoneal cavity cancer -- fallopian tube cancer - Up to 2 previous chemotherapies; the most recent must have been a platinum- containing therapy - Progression of disease or symptomatic relapse during, or within 6 months of previous therapy - 4 weeks or more since prior radiotherapy or chemotherapy - 3 weeks or more since prior immunotherapy - Adequate recovery from previous surgery, radiotherapy, and chemotherapy ( excluding alopecia) - Survival expectation of 3 months or more Exclusion Criteria: - More than 2 previous chemotherapies - Previous treatment with epothilones - Use of any investigational drug within 4 weeks of start of study treatment or inadequate recovery from any toxic effects of such therapy - Previous radiation to the whole pelvis - Symptomatic brain metastases requiring whole-brain irradiation - Active infection - Any other malignancy except: -- Non-melanoma skin cancer -- Carcinoma in situ of cervix -- Malignancy with treatment 5 or more years ago without relapse - Mixed mesodermal tumor - Prior hormone therapy for any malignancy in the previous month - Women of childbearing potential

Study Objectives This pilot study is designed to evaluate the safety and tolerability of oral crenolanib besylate given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3 activating mutations. Conditions: Newly Diagnosed AML With FLT3 Activating Mutations Intervention / Treatment: DRUG: crenolanib, DRUG: cytarabine, DRUG: daunorubicin, DRUG: idarubicin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Unequivocal diagnosis of AML based on the WHO classification, excluding acute promyelocytic leukemia * No prior therapy for AML, except for hydroxyurea, in this setting is allowed. * Subjects with AML evolving from MDS may have received prior MDS therapy with demethylating agents * Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations * Age ≥18 years * ECOG PS 0 - 2 * Adequate liver function, defined as normal total bilirubin, ALT ≤2.0x ULN, and AST ≤2.0x ULN measured within 24 hours prior to crenolanib commencement * Adequate renal function, defined as serum creatinine ≤1.5x ULN or GFR >50 mL/min * Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP) * Women considered not of childbearing potential include any of the following: no menses for at least 2 years or menses within 2 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months or with bilateral tubal ligation * WOCBP must practice contraception. Acceptable methods of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, tubal ligations, and abstention * Male patients (except those with prior surgical contraceptive procedures) with female partners who are of childbearing potential: Recommendation is for male and partner to use effective contraceptive methods, such as latex condoms, during the study * Able and willing to provide written informed consent Exclusion Criteria: * Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.) * Active CNS leukemia * Subject with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy * NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy * Unable to swallow pills * Major surgical procedures within 14 days of administration of crenolanib (does not include line placement as needed for chemotherapy administration). * Unwillingness or inability to comply with protocol. * Concurrent use of other investigational agents. * Subjects who are not eligible for standard chemotherapy

Study Objectives This was a Phase II, multicenter, non-randomized, open-label study to assess the efficacy, safety, and tolerability of dabrafenib administered as a single agent and in combination with trametinib in stage IV disease to subjects with BRAF mutant advanced non-small cell lung cancer. Central confirmation testing for the BRAF V600E mutation was performed and a sufficient number of subjects were enrolled with the intent of having at least 125 centrally confirmed subjects among the three cohorts. Conditions: Cancer Intervention / Treatment: DRUG: Dabrafenib, DRUG: Trametinib Location: Norway, Germany, Japan, Korea, Republic of, Italy, Netherlands, Spain, United Kingdom, United States, Taiwan, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed written informed consent; * Histologically or cytologically confirmed non-small cell cancer of the lung (NSCLC) stage IV (accordingto AJCC Staging 7th Edition); * For Cohorts A and B, documented tumor progression (based on radiological imaging) after receiving at least one prior approved platinum-based chemotherapy regimen for advanced stage/metastatic NSCLC. An alternate chemotherapeutic agent/regimen is an acceptable substitute in the event that the subject was intolerant to, or ineligible to receive platinum based chemotherapy. Subjects enrolled in Cohort B cannot have more than 3 prior systemic treatments for advanced stage/metastatic NSCLC (neoadjuvant and adjuvant therapies are not counted in number of prior regimens and maintenance therapy is not counted as a separate regimen). Subjects in Cohort C will be required to have not received prior systemic anti-cancer therapies for metastatic disease (i.e., dabrafenib/trametinib will be 1st line treatment for metastatic disease); * Measurable disease according to Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]; * At least 18 years of age; * Anticipated life expectancy of at least three months; * Presence of a BRAF V600E mutation in lung cancer tissue. Mutation must be locally confirmed in a CLIA-certified laboratory (or equivalent). An adequate amount of tumor tissue (archived tumor tissue, or fresh biopsy if archived tissue is not available) must be available at the time of enrolment for central validation of BRAF mutation; * Able to swallow and retain oral medication; * Women of childbearing potential must have a negative serum pregnancy test within 14 days before the first dose of study treatment and agree to use effective contraception during the study; NOTE: Oral contraceptives are not reliable due to potential drug-drug interaction with dabrafenib. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2; * Must have adequate organ function as defined by the following baseline values: Absolute neutrophil count (ANC) >=1.5x10\^9/L Hemoglobin >=9 g/dL Platelets >=100x10\^9/L Prothrombin time /International normalized ratio (INR) and partial thromboplastin time <=1.5xULN (Subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to starting study treatment.) Total bilirubin <=1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5xULN Serum creatinine <=1.5 mg/dL (if serum creatinine is >1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault; creatinine clearance must be > 50 mL/min); creatinine clearance should be >= 50 mL/min Left ventricular ejection fraction >= institutional lower limit of normal ECHO * French subjects: 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 * Previously tested for presence of EGFR and ALK mutations in lung cancer tissue confirmed in a CLIA-certified laboratory (or equivalent). Subjects with EGFR or ALK mutation are eligible if they have previously received EGFR or ALK inhibitor(s) respectively. Exclusion Criteria: * Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, LGX818, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) prior to start of study treatment (Note: Prior treatment with dabrafenib is allowed for crossover subjects in Cohort A); * Anti-Cancer therapy including chemotherapy, radiation-therapy, immunotherapy, biologic therapy or major surgery within 14 days prior to start of study treatment (Note: Dabrafenib monotherapy within 14 days prior to starting combination therapy is allowed for crossover subjects in Cohort A); * Use of any investigational anti-cancer drug within 14 days or 5-half-lives (minimum 14 days), prior to start of study medication (Note: Dabrafenib monotherapy within 14 days prior to starting combination therapy is allowed for crossover subjects in Cohort A); * Current use of a prohibited medication or expected to require any of these medications during treatment with study treatment. * Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia; * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GSK medical monitor for guidance to enrol the subject; * Known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection may be enrolled; * History of another malignancy < 3 years prior to starting study treatment or any malignancy with confirmed activating RAS-mutation; Exceptions: Subjects with any of the following malignancies within 3 years (does not include malignancies with confirmed activating RAS-mutation) are eligible: (a) a history of completely resected skin cancer, (b) successfully treated in situ carcinoma, (c) chronic lymphocytic lymphoma (CLL) in stable remission, or (d) indolent prostate cancer (definition: clinical stage T1 or T2a, Gleason score <= 6, and prostate specific antigen \[PSA\] < 10 ng/mL) requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from lung cancer target and non-target lesions are eligible * Subjects with brain metastases are excluded if their brain metastases are: * Symptomatic OR * Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy(as assessed by contrast enhanced magnetic resonance imaging \[MRI\] or computed tomography \[CT\]), OR * Asymptomatic and untreated but >1 cm in the longest dimension * A history or evidence of cardiovascular risk including any of the following: Corrected QT (QTc) interval >=480 msecs History of acute coronary syndromes (including myocardial infarction or unstable angina) within 6 months prior to first dose of study treatment Coronary angioplasty, or stenting within the past 24 weeks; A history or evidence of current Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) guidelines; Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by antihypertensive therapy; Abnormal cardiac valve morphology ( >=Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities \[i.e., mild regurgitation/stenosis\] can be entered on study). Subjects with moderate valvular thickening should not be entered on study; Patients with intra-cardiac defibrillators A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible. Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc.), psychological, familial, sociological, or geographical conditions that interfere with the subject's safety or obtaining informed consent or do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol; * Pregnant, or actively breastfeeding females. * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO) * Additional Exclusion Criteria for dabrafenib and trametinib combination therapy (Cohort B and C as well as subjects that crossover from monotherapy to combination therapy): * History of interstitial lung disease or pneumonitis * A history or current evidence of retinal vein occlusion (RVO).

Study Objectives The goal of this clinical research study is find the highest tolerable dose of BMTP-11 when given to patients with prostate cancer that has spread. The safety of this drug will also be studied. Conditions: Prostate Cancer Intervention / Treatment: DRUG: BMTP-11 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: * Have histologically confirmed adenocarcinoma of the prostate, with clinically significant bone metastases exhibiting castrate-resistant progression. Progression is defined as any of the following: 1) New lesions or obviously worsening lesions on bone scan within the previous three months; 2) a PSA doubling time of < 3 months; 3) New or progressive symptoms requiring a change in therapy that are referable to the cancer; 4) New extra-osseous lesions within the past 3 months * Have progression in the face of a serum testosterone of less than 50 ng/dL, and have either failed or refused chemotherapy * Have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 * Have adequate bone marrow function defined as an absolute peripheral granulocyte count of >= 1,000/mm\^3 and platelet count of >= 140,000/mm\^3; hemoglobin >= 9.0 g/dL (without transfusion or growth factor support), unless the patient is < 6 weeks from last cancer therapy in which case transfusion is allowed. * Have adequate hepatic function defined as a total bilirubin of <= 1.5 mg/dl and AST <= 2\* the upper limits of normal * Have adequate renal function defined as serum creatinine <= 1.5\* the upper limits of normal or creatinine clearance >= 60 mL/min (measured or calculated). In the absence of hematuria, patients must have either a negative urinalysis for protein (i.e. no more than "trace" by dipstick) or a 24 hour urine collection showing less than 1,000 mg of protein/24 hour. In the presence of hematuria, patients may have up to 2,000 mg of protein/24 hour. * Have adequate cardiovascular function as defined by: i) a normal beta-natruetic peptide (BNP) with ii) no signs or symptoms suggestive of cardiac disease and iii) a normal Electrocardiography (ECG). Alternatively, patient not meeting all of these criteria is still eligible if he has both i) an echocardiogram showing an ejection fraction (EF) of 45% or greater (and no more than "mild" diastolic dysfunction) and ii) a Brain Natriuretic Peptide (BNP)of < 200 * Sign the current Institutional Review Board (IRB) approved informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution * Age >= 18 years old Exclusion Criteria: * Small cell prostate cancer * Infectious process, which, in the opinion of the investigator, could worsen or its outcome be affected, as a result of the investigational therapy * Any of the following in previous 6 months: New York Heart Association (NYHA) Class III/IV congestive heart failure, unstable angina, cerebrovascular accident (including transient ischemic attack), pulmonary embolism or myocardial infarction (by ECG or serologic criteria) * Significant co-morbidity that could affect the safety or evaluability of participants, including: a) Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 140 or diastolic pressures above 90 despite therapy. Note that this is NOT a criterion related to particular BP results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes. (Please see further explanation in the Treatment Plan below) * (# 4 cont'd) b) uncontrolled diabetes mellitus (defined as Hgb A1c > 8.5, or symptomatic hypoglycemic episodes > 1 per week during the two months prior to eligibility evaluation, or more than 1 glucose excursion to >300 mg/dL in prior two months--unless clearly iatrogenic and the cause has been eliminated),c) lung disease requiring supplemental oxygen, d) known chronic liver disease, or e) HIV infection * Hydronephrosis (either bilateral or involving a solitary kidney) that has not been addressed by means of a nephrostomy or indwelling stent. (Non-obstructive hydronephrosis in setting of prior urinary diversion is allowed.) * Overt psychosis, mental disability or being otherwise incompetent to grant informed consent or a history of non-compliance with medical care * Patients must not require ongoing therapy with non-steroidal anti-inflammatories (NSAIDs),other than low-dose (i.e. 81 mg or less) aspirin daily, i.v. vancomycin, aminoglycosides, or other potently nephrotoxic drugs, and must agree to abstain from NSAIDs for the duration of their participation in the trial * Any other medical condition that in the opinion of the principal investigator would compromise the ability to deliver or evaluate study drug * Unwillingness to maintain adequate contraception measures for the entire course of the study * Any therapy for prostate cancer (other than ongoing androgen deprivation or associated hormonal therapies such as diethylstilbesterol, low-dose dexamethasone, megace, etc) in the two weeks prior to starting BMTP-11

Study Objectives This study will evaluate the use of nivolumab before surgery in patients with high-risk clear cell renal cell carcinoma who are eligible for nephrectomy. Nivolumab is an antibody that may help activate the immune system by blocking the function of an inhibitory molecule, Programmed cell death-1 (PD-1). Conditions: Clear Cell Renal Cell Carcinoma Intervention / Treatment: DRUG: Nivolumab 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 (abbreviated): * Confirmed non-metastatic high-risk clear cell renal cell carcinoma (T2a-T4NanyM0 or TanyN1M0) * Schedule to undergo either partial or radical nephrectomy as part of treatment plan * Patient agrees to have a tumor biopsy * ECOG performance status of 0 or 1 * Adequate organ and marrow function defined by study-specified laboratory tests * Must use acceptable form of birth control while on study and for approximately 31 weeks post-treatment completion * Willingness and ability to comply with scheduled visits, treatment plans, lab tests and other study procedures Exclusion Criteria (abbreviated): * Other active malignancies within last 3 years (with some exceptions for skin, prostate, cervical, or breast cancer) * Need for urgent or emergent nephrectomy to relieve symptoms * Prior treatment for RCC including surgery, radiation, thermoablation or systemic therapy * Surgery within 28 days of starting study treatment (some exceptions for minor procedures) * Received live vaccine for infectious diseases within 28 days of starting study treatment * Prior treatment with any antibody or drug targeting T-cell costimulation or immune checkpoint pathways (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, etc) * Use of immunosuppressive doses of systemic medications within 14 days prior to starting study drug. * Current use of immunosuppressive agents * History of severe hypersensitivity reaction to other monoclonal antibodies * Current signs or symptoms of severe progressive or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC * Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements. * Active infection requiring therapy. * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. * Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA). * History of autoimmune disease or syndrome requiring systemic steroids or immunosuppressants (some exceptions apply). * Pulse oximetry of <92% on room air * Pregnant or breastfeeding women

Study Objectives The purpose of this study is to compare the effects, good and/or bad, of posaconazole and micafungin in preventing fungal infections after chemotherapy for acute leukemia or myelodysplastic syndrome. When people take chemotherapy, they are more likely to get infections. Posaconazole has been approved for the prevention of fungal infections in patients who receive induction chemotherapy for acute leukemia and myelodysplastic syndrome. Posaconazole is available only as an oral suspension and has to be given with food. After chemotherapy, many patients are not able to tolerate food or oral medication because of severe mucositis. Patients unable to tolerate food and oral medications cannot take posaconazole. Micafungin is an antifungal medication that is given only intravenously. Micafungin is approved for the treatment of certain fungal infections and for preventing fungal infections in patients who receive bone marrow transplant. The investigators know that micafungin is safe. Micafungin has not been tested for the prevention of fungal infections in patients receiving chemotherapy for acute leukemia and myelodysplastic syndrome. Because micafungin is given by vein, it can be given even in patients who cannot take food or medications by mouth after chemotherapy. In this study the investigators want to compare micafungin to posaconazole when given for the prevention of fungal infections in leukemia and myelodysplastic syndrome patients. Conditions: Acute Myelogenous Leukemia, Myelodysplastic Syndrome Intervention / Treatment: DRUG: micafungin, DRUG: posaconazole Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Subjects of greater than or equal to 18 years of age of either sex and of any race. Disease definition: * Anticipated or documented prolonged neutropenia (ANC<500/mm3 \[0.5x109/L\]) at baseline or likely to develop within 3 to 5 days and lasting for at least 7 days due to: * Intensive induction chemotherapy for new diagnosis of acute myelogenous leukemia, acute lymphocytic leukemia or myelodysplastic syndrome receiving standard anthracycline based chemotherapy * Re-induction of acute myelogenous or lymphocytic leukemia after primary relapse * Myelodysplastic syndromes requiring induction (myelosuppressive) chemotherapy * Female subjects of childbearing potential must have a negative serum pregnancy test as per MSKCC guidelines. * Able to swallow oral medications Exclusion Criteria: * Subjects with history of presumed or proven invasive fungal infection within 30 days of randomization. * Subjects who are taking the following: Drugs known to interact with posaconazole and that may lead to life-threatening side effects (terfenadine, cisapride, and ebastine at entry or within 24 hours before entry, or astemizole at entry or within 10 days before entry); b. Drugs known to lower the serum concentration/efficacy of posaconazole: cimetidine, rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, and isoniazid at entry or within 24 hours before entry; c. Subjects who are planned to receive > 2mg flat dose of vinca alkaloids. * Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents. * Subjects with renal insufficiency (estimated creatinine clearance less than 20 mL/minute at baseline or likely to require dialysis during the study). * Subjects having an electrocardiogram with a prolonged QTc interval by manual reading: QTc greater than 490 msec. * Subjects with moderate or severe liver dysfunction at baseline, defined as aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase levels greater than 5 times the upper limit of normal (ULN), or a total bilirubin level greater than 3 times the ULN. * Subjects who are undergoing re-induction chemotherapy and have participated in this study during their first induction chemotherapy. * Subjects who will be receiving dasatinib.

Study Objectives This study is to characterize the indications for which rituximab is being used and to evaluate the use of the Patient Alert Card (PAC) in participants receiving the medication for non-oncology conditions at infusion centers. The study involves the retrospective chart review of rituximab users' medical records in non-oncology indications as well as a survey to collect information on participant characteristics, and will include questions about participant knowledge on the risk of infections, participant receipt and review of the PAC, and any actions the participant has taken as a result of receiving the PAC. Conditions: Off-Label Use Intervention / Treatment: BIOLOGICAL: Rituximab Location: Germany, Italy, Spain, United Kingdom, France Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Participant is in the center to receive an infusion for rituximab for a non-oncology indication during the study period * Aged 18 years or older Exclusion Criteria: * Has previously already completed the rituximab survey * Has participated in the past 12 months in a clinical trial in which rituximab was one of the treatments being evaluated.

Study Objectives This phase I/II trial is studying the side effects of giving laboratory-treated T cells and ipilimumab together to see how well they work in treating patients with metastatic melanoma. Treating a patient's T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving laboratory-treated T cells together with ipilimumab may kill more tumor cells Conditions: Recurrent Melanoma, Stage IV Melanoma Intervention / Treatment: BIOLOGICAL: ipilimumab, DRUG: cyclophosphamide, PROCEDURE: biopsy, BIOLOGICAL: aldesleukin, OTHER: immunohistochemistry staining method, GENETIC: polymerase chain reaction, OTHER: immunoenzyme technique, BIOLOGICAL: therapeutic cytotoxic T lymphocytes Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: SINGLE

Inclusion Criteria: * Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease * Expression of human leukocyte antigen (HLA)-A2 * Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1 * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized; suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal * Men must be willing and able to use an acceptable method of birth control, for at least 3 months after completion of the study, if their sexual partners are WOCBP * Willing and able to give informed consent * Adequate venous access-consider peripherally inserted central catheter (PICC) or central line * Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography \[CT\] scan) * At least 4 weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery; at least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin; if started before T-cell administration, Ipilimumab infusions must be least 21 days apart * Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible * Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped Exclusion Criteria: * Patients with active infections or oral temperature > 38.2 C within 72 hours prior to planned leukapheresis; the procedure may be deferred * Patients with hematocrit (Hct) < 30%, white blood cells (WBC) < 2500/uL and platelets < 50,000 immediately prior to leukapheresis; the procedure may be deferred * Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix * White blood cell count (WBC) < 2000/uL * Hematocrit (Hct) < 24% or hemoglobin (Hb) < 8 g/dL * Absolute neutrophile count (ANC) < 1000 * Platelets < 50,000 * Creatinine > 3.0 x upper limit normal (ULN) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN * Bilirubin > 3 x ULN * Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception; women of childbearing potential with a positive pregnancy test within 3 days prior to entry * Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusion capacity of carbon monoxide (DLco) (corr for Hgb) < 50% will be excluded * Significant cardiovascular abnormalities as defined by any one of the following: * Congestive heart failure * Clinically significant hypotension * Symptoms of coronary artery disease * Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy * Ejection fraction < 50 % (echocardiogram or multi gated acquisition \[MUGA\] scan) * Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening magnetic resonance imaging \[MRI\] or contrast CT) * Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable * Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea * Positive screening tests for human immunodeficiency virus (HIV), hepatitis (Hep) B, and Hep C; if positive results are not indicative of true active or chronic infection, the patient can be treated * Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy * No prisoners or children will be enrolled on this study * Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose * Patients may not be on any other treatments for their cancer aside from those included in the protocol; patients may not undergo another form of treatment concurrently with this study

Study Objectives The main purpose of this study is to determine the anti-tumor activity of MEDI4736 in combination with tremelimumab in patients with metastatic HER2-negative breast cancer. Both MEDI4736 and tremelimumab are antibodies (proteins used by the immune system to fight infections and cancers). MEDI4736 attaches to a protein in tumors called PD-L1. It may prevent cancer growth by helping certain blood cells of the immune system get rid of the tumor. Tremelimumab stimulates (wakes up) the immune system to attack the tumor by inhibiting a protein molecule called CTLA-4 on immune cells. Combining the actions of these drugs may result in better treatment options for patients with breast cancer. Conditions: Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative, Recurrent Breast Carcinoma, Stage IV Breast Cancer Intervention / Treatment: BIOLOGICAL: Anti-B7H1 Monoclonal Antibody MEDI4736, OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study, BIOLOGICAL: Tremelimumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have a histologically documented (either primary or metastatic site) diagnosis of breast cancer that is HER2 non-overexpressing by immunohistochemistry, namely 0 or 1; if they have an equivocal immunohistochemistry, 2, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio < 2 and HER2 copy number < 4); estrogen receptor (ER) positivity is defined as 1% or greater * Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria * Patients who are ER negative must have progressed through at least one prior chemotherapy regimen in the metastatic setting or within 12 months of their last adjuvant systemic treatment; patients who are ER positive must have progressed through standard hormone therapy options and have received at least one line of chemotherapy in the metastatic setting * Completion of prior chemotherapy systemic anticancer therapy at least 2 weeks prior to study entry * Radiation therapy must be completed at least 2 weeks prior to study entry; radiated lesions may not serve as measurable disease unless they have been radiated over 12 months prior to enrollment * Patients may have parenchymal brain metastases if stable (no evidence of progression) for at least 1 month after local therapy (radiation or surgery); leptomeningeal disease is excluded; must have completed any prescribed steroid taper * Patients may have had a prior diagnosis of cancer if it has been > 5 years since their last treatment * Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 * Absolute neutrophil count >= 1,000/mcL * Platelets >= 50,000/mcl * Total bilirubin =< 1.5 times the institutional upper limit of normal (ULN) (or =< 3 times ULN in case of liver metastasis) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SPGT\]) =< 2.5 X institutional ULN (or =< 5 times ULN in case of liver metastasis) * Creatinine =< 2 ng/ml * Females of child-bearing potential (FOCBP) and males must agree to use 2 methods of adequate contraception prior to study entry, for the duration of study participation, and for number (#) days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months) * FOCBP must have a negative pregnancy test within 7 days prior to registration on study * Willingness to provide a fresh biopsy prior to study enrollment and after 2 cycles of treatment * Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are not eligible. * Current or prior use of immunosuppressive therapy within 2 weeks of starting investigational therapy * Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration for at least 2 weeks; NOTE: Vitamin supplements are acceptable * Patients may not have received any other investigational agents within 4 weeks prior to registration * Prior treatment with immune therapy (including but not limited to cluster of differentiation \[CD\]137, OX40, programmed death \[PD\]-1, PD-L1 or cytotoxic T-lymphocyte antigen 4 \[CTLA4\] inhibitors) * Prior severe infusion reaction to a monoclonal antibody * Patients with a history of or active autoimmune disease within the past 3 years with the following exceptions: * Vitiligo or alopecia * Hypothyroidism on stable doses of thyroid replacement therapy * Psoriasis not requiring systemic therapy within the past 3 years * History of primary immunodeficiency disease or tuberculosis * Major medical conditions that might affect study participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) are not eligible; other significant comorbid condition which the investigator feels might compromise effective and safe participation in the study * Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible: * Uncontrolled pulmonary, renal, or hepatic dysfunction * Ongoing or active infection requiring systemic treatment * Known active or chronic viral hepatitis or human immunodeficiency virus (HIV) * Psychiatric illness/social situations that would limit compliance with study requirements * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints * Female patients who are pregnant or nursing are not eligible

Study Objectives The purpose of this study is to investigate if androgen deprivation therapy in men with prostate cancer increases hepatic fat content and changes visceral/subcutaneous fat distribution. Conditions: Prostate Cancer, Metabolic Syndrome, Hypogonadism, Fatty Liver Intervention / Treatment: DRUG: Triptorelin, PROCEDURE: Orchiectomy Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Eligible for inclusion are patients who are included in the already ongoing Randomised trial entitled: Metabolic Changes Due to Iatrogenic Hypogonadism in Patients With Prostate Cancer: Orchiectomy vs. Triptorelin (EudraCT number: 2013-002553-29) Exclusion Criteria: * Implanted devices or foreign metallic bodies incompatible with Magnetic Resonance Imaging. * claustrophobia * Severe Psychiatric disease

Study Objectives The purpose of this study is to investigate if zalutumumab in combination with Best Supportive Care (BSC) is superior to BSC in non-curable patients with head and neck cancer Conditions: Head and Neck Cancer, Squamous Cell Cancer Intervention / Treatment: DRUG: Zalutumumab, OTHER: Control Location: Hungary, Estonia, Canada, Lithuania, Brazil, United Kingdom, Serbia, Belgium, Russian Federation, Sweden, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Males and Females age ≥ 18 years * Confirmed diagnosis, initially or at relapse, of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, considered incurable with standard therapy * Failure to at least one course of standard platinum-based chemotherapy Exclusion Criteria: * Three or more chemotherapy regimens other than platinum-based chemotherapy * Prior treatment with EGFr antibodies and/or EGFr small molecule inhibitors * Past or current malignancy other than SCCHN, except for certain other cancer diseases

Study Objectives The purpose of this study is to assess the toxicity of PS-341 combined with one of four doses of thalidomide in patients with refractory multiple myeloma, and to find the most appropriate doses of PS-341 and thalidomide in the combination. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: PS-341, DRUG: Thalidomide, DRUG: Dexamethasone 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: * History of histologically documented multiple myeloma with relapsed or resistant disease, defined as previously treated with/without autologous stem cell transplantation and is either relapsing or is resistant after > 1 line of prior therapy for myeloma * Patients can not be eligible for MTRC phase III protocols of higher priority * Performance status of greater than or equal to 2 as per SWOG scale * Patients must have an absolute neutrophil count > 750/mm3, and a platelet count greater than or equal to 25,000/mm3 * No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years. Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval * Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Male or female adults of at least 18 years of age. * Signed written informed consent and willingness to meet follow-up schedule and study procedure obligations Exclusion Criteria: * Chemotherapy or radiotherapy received within the previous 2 weeks * Prior Treatment of PS-341 * Significant neurotoxicity, defined as grade greater than or equal to 2 neurotoxicity per NCI Common Toxicity Criteria * POEMS Syndrome * Non-secretory multiple myeloma * Active infection requiring antibiotics * Clinically significant hepatic dysfunction in the absence of liver metastases as noted by bilirubin or AST >3 times the upper normal limit or clinically significant concurrent hepatitis * New York Hospital Association (NYHA) Class III or Class IV heart failure * Myocardial infarction within the last 6 months * Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol * Severe renal dysfunction defined as a creatinine clearance < 20 cc/min. * Absolute neutrophil count < 750/mm3, and a platelet count < 25,000/mm3 * Pregnant or potential for pregnancy * Breast-feeding

Study Objectives This phase Ib trial studies the side effects of combination chemotherapy and donor stem cell transplant followed by ixazomib citrate maintenance therapy in treating patients with multiple myeloma that has returned after a period of improvement and is likely to recur (come back), or spread. Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving ixazomib citrate after the transplant may improve the overall treatment outcome without causing additional toxicities. Conditions: Plasma Cell Leukemia, Recurrent Plasma Cell Myeloma Intervention / Treatment: PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Carmustine, DRUG: Cytarabine, DRUG: Etoposide, DRUG: Ixazomib Citrate, DRUG: Melphalan, DRUG: Methotrexate, PROCEDURE: Peripheral Blood Stem Cell Transplantation, OTHER: Quality-of-Life Assessment, DRUG: Tacrolimus 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: * Relapsed multiple myeloma in patients that have been treated previously with autologous hematopoietic stem cell transplantation (auto-HCT), bortezomib and an immunomodulatory agent, AND with at least one of the following high-risk criteria * High-risk multiple myeloma defined by cytogenetic or fluorescence in situ hybridization (FISH) detection of any one or more of the following: * Deletion 17p * Translocation t(4;14) * Translocation t(14;16) * Translocation t(14;20) * Chromosome 1q gain * Chromosome 1p deletion * Deletion 13q by conventional karyotyping (FISH only not acceptable) * Hypodiploidy * High-risk gene expression profiling (GEP) at the time of relapse * Beta-2 (B2) microglobulin > 5.5 mg * Plasmablastic morphology (> 2%) * Relapsed plasma cell leukemia * Chemo-sensitive disease; patients with relapsed plasma cell leukemia may have received systemic therapy including an autologous transplant but it is not required; patients with relapsed multiple myeloma (MM) must have received prior systemic therapy including an autologous transplant; patient must be in at least a PR at the time of transplant; early relapse from complete response will be allowed * Measurable disease at the time of relapse, defined as a monoclonal immunoglobulin spike on serum electrophoresis of >= 1 gm/dL (immunoglobulin \[IG\]G) or >= 0.5 gm/dL (IGA) and/or urine monoclonal immunoglobulin spike of > 200 mg/24 hours and/ or involved free light chain (FLC) level >= 10 mg/dl and the serum FLC ratio is abnormal * Non-secretors must have measurable disease such as plasmacytomas, or positron emission tomography (PET) avid lytic lesions or bone marrow plasmacytosis >= 30% at the time of relapse to be eligible * The patient must have an available sibling or matched unrelated donor with at least a 7/8 human leukocyte antigen (HLA) match * Creatinine =< 2.0 mg/dL * Ejection fraction >= 45% * Diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50% * Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) >= 50% predicted * Both men and women and members of all races and ethnic groups will be included * Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%) * Willing to use adequate contraception for the duration of time on the study and for 90 days after the last therapy * Female patients must meet one of the following: * Postmenopausal for at least 1 year before the screening visit, OR * Surgically sterile, OR * If they are of childbearing potential: * Agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) * Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care * DONOR: HLA genotypically identical sibling matched relative * DONOR: HLA matched unrelated donor according to Standard Practice HLA matching criteria: * Matched HLA-A, -B, -C, and -DRB1 alleles by high resolution typing * Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing Exclusion Criteria: * Previous allogeneic stem cell transplant * POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[protein\] and skin changes) * Bilirubin > 1.5 x the upper limit of normal * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x the upper limit of normal * Patients with >= grade III or grade II with pain peripheral neuropathy (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 4.03 criteria) * Receiving steroids > the equivalent of 10 mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosus, rheumatoid arthritis * Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment * Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive * Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months * Second malignancy requiring concurrent treatment or those with non-hematological malignancies (except non-melanoma skin cancers); cancer treated with curative intent < 5 years previously will not be allowed unless approved by the protocol chair; cancer treated with curative intent > 5 years previously is allowed * Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol * Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent * Radiotherapy within 14 days before enrollment; if the involved field is limited to a single site, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib * Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort * Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing * Female patients who are lactating or have a positive serum pregnancy test during the screening period * Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible effects of prior chemotherapy * Major surgery within 14 days before enrollment * Central nervous system involvement * Participation in other clinical treatment trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial * DONOR: Identical twin * DONOR: Donors unwilling to donate PBSC * DONOR: Pregnancy * DONOR: Infection with HIV * DONOR: Inability to achieve adequate venous access * DONOR: Known allergy to filgrastim (G-CSF) * DONOR: Current serious systemic illness * DONOR: Failure to meet institutional criteria for stem cell donation * DONOR: Patient and donor pairs must not be homozygous at mismatched allele

Study Objectives The primary objective of the study is to evaluate the effect of rifampicin on pharmacokinetics of healthy adult subjects after oral administration of HRS-1167 tablets. The secondary objective of the study is to evaluate the safety of HRS-1167 alone and when co-administered with rifampicin. Conditions: Advanced Solid Tumor Intervention / Treatment: DRUG: HRS-1167 tablets; rifampicin Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Healthy adult subjects aged 18 to 50 years old at the date of signing the informed consent; * Weight ≥ 50 kg for male, weight ≥ 45 kg for female, body mass index (BMI): 19\~28 kg/m2 (including critical value); * Female patients of childbearing age who are not surgically sterilized and male patients whose partners are women of childbearing age must use highly effective contraceptive measures from the signing of the informed consent form to 6 months after the last dose of HRS-1167; female patients of childbearing age who are not surgically sterilized must have a negative serum HCG test within 7 days before the first dose, and must be non-lactating; * Be able to communicate well with the investigators and understand and comply with the requirements in this study. Exclusion Criteria: * History of or currently suffering from any serious clinical diseases such as diseases in circulatory system, endocrine system, nervous system, digestive system, respiratory system, genitourinary system, hematology, immunology, psychiatry, and metabolic abnormalities, or any other diseases may interfere with the test results * Any surgery within 6 months before screening, or plan to perform surgery during the study period, or who have previously undergone any surgery that affects gastrointestinal absorption (including gastrectomy, bowel resection, gastric reduction surgery, etc.); * Those who donate blood or other reasons of bleeding cause the total loss of blood more than 400mL, or receive blood transfusions, or used blood products within 3 months before screening; * Allergic constitution, including severe drug allergy or history of drug allergy; Have allergic history to HRS-1167 tablets, rifampicin, rifamycin or their accessories; * Frequent use of sedatives, sleeping pills or other addictive drugs; History of drug abuse within 1 year prior to screening; Positive for urine drug abuse screening test; * Have taken hepatotoxic drugs (such as dapsone, erythromycin, fluconazole, ketoconazole, rifampicin, etc.) for a long time (continuous administration for more than 7 days) within 6 months before screening; * Those who have participated in any clinical trials and taken study drugs within 3 months before the first administration; * Have used any drugs that effect enzyme activity within 28 days prior to taking the study drug; * Used any prescription drugs and Chinese medicines within one month before the first administration; Have used any over-the-counter drugs (OTC) or food supplements (including vitamins and calcium tablets, etc.) within 2 weeks prior to the first administration; * Those who smoke more 5 cigarettes per day in the 3 months before screening or those who do not agree to quit smoking during the test, or those who are positive for urine nicotinic screen; * Alcohol abuse in the 6 months prior to screening, with an average weekly intake of more than 14units of alcohol (1 unit = 285 mL of beer, 25 mL of spirits, or 100 mL of wine), and those who cannot abstain from alcohol during the trial, or those who have a positive alcohol breath screening; * The results of vital signs, physical examination, 12-lead electrocardiogram, B-ultrasound, chest X-ray, blood-routine examination, blood biochemistry, urine-routine examination, and coagulation function are abnormal during the screening and judged by the research doctor as clinically significant. * Those who are positive for HBsAg, HCV antibody, syphilis antibody and HIV antibody. * From 48 hours before taking the study drug to the end of the study, subjects have xanthine-rich beverages (chocolate, coffee, tea, etc.) or food; From 7 days before taking the study drug to the end of the study, subjects have; Can't comply with the unified dietary arrangement or have special requirements for diet; * Who have blood phobia and faint with acupuncture; or those with poor vascular conditions, inability to embed needles or inability to tolerate venipuncture; * Pregnant and lactating women; * Subjects who are judged by researchers to be unsuitable for participating in this test.

Study Objectives A multi-center , opened, Phase II study to assess the efficacy and safety of Sulfatinib 300 mg Sulfatinib in advanced Medullary Thyroid Carcinoma ( MTC) and iodine-refractory differentiated thyroid carcinoma (DTC). Conditions: Thyroid Carcinoma Intervention / Treatment: DRUG: Surufatinib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Informed consent must be obtained in writing for all subjects before enrollment into the study; * Age 18 years or older * Subjects must have histologically or cytologically confirmed diagnosis of locally advanced and/ or metastatic MTC or iodine-refractory DTC (papillary, follicular , Hürthle cell and other variable type carcinoma), losing the surgical indications or can't undertake external radiotherapy * Subjects must show evidence of disease progression within 12 months (assessed and confirmed by central radiographic review of CT and/or MRI scans) before initial treatment of this study * Subjects must be I-refractory / resistant as defined by at least one of the following: One or more measurable lesions that has progressed by CT and/or MRI scans within 12 months of Iodine-131 (131I) therapy; One or more measurable lesions that do not demonstrate 131I uptake on any radioiodine scan ; Cumulative activity of 131I of > 600 millicurie or 22 gigabecquerel (GBS), and independently reviewed radiologic evidence of progression within the previous 12 months before initial treatment of this study * At least 6 months of last dose administered prior to study treatment * Subjects may have received 0 or 1 prior vascular endothelial growth factor (VEGF)/VEGFR-targeted therapy (for example , patients with MTC have received vandetanib or cabozantinib; patients with DTC have received sorafenib or lenvatinib) or other targeted inhibitors * Subjects with DTC, serum thyroid-stimulating hormone (TSH) concentration should be lower than 0.1 milliunits per litre (mU/L) (or other corresponding units) before enrollment into the study; Subjects with MTC, levels of serum TSH concentration should be in the normal range * Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 * Subjects must have measurable lesions meeting the criteria of Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * The expecting life scan was more than 12 weeks * Females or Males of childbearing potential must agree to use a highly effective method of contraception (e.g., a double-barrier method, condom, a injective or oral contraceptive, an intrauterine device) throughout the entire study period and for 90 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal. Exclusion Criteria: * Absolute neutrophil count 1.5×109/L, or platelet<100 ×109/L, or hemoglobin< 9g/dL * Serum bilirubin >1.5 the upper limit of normal (ULN) * Serum alanine transaminase (ALT) , aspartate aminotransferase (AST) or Alkaline phosphatase (ALP) ≥2.5 ULN (Patients with documented disease infiltration of the liver may have ALT, AST or ALP levels ≥ 5 the ULN) * Serum creatinine≥1.5 the upper limit of normal (ULN) , or estimated creatinine clearance < 60 mL/min * Subjects having≥2+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein≥1g/24 h will be ineligible * International normalized ratio (INR) ≥1.5 the ULN or activated partial thromboplastin time (aPTT) ≥1.5 the ULN (For patients requiring anticoagulation therapy with warfarin, a stable INR between 2-3 is required) * Serum potassium, calcium (albumin-bound ionic or corrected) or magnesium exceed the normal range with clinical significance * Active hypertension (systolic pressure≥140mm Hg, or diastolic pressure ≥90mm Hg) that drugs can't control * Gastrointestinal disease or condition that investigators suspect may affect drug absorption, including but not limited to, previously subtotal gastrectomy surgery, active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that may cause bleeding or perforation by investigator's discretion * History or presence of a serious hemorrhage (>30 ml within 3 months), hemoptysis (>5 ml blood within 4 weeks) or a thromboembolic event (including transient ischemic attack) within 12 months * Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification ≥ 2; ventricular arrhythmias which needs drug treatment; LVEF (LVEF) <50% * Prolongation of QT interval to≥480 ms * Active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 5 years * Patients were excluded from the study if they had received anti-tumor therapies, including but not related to chemotherapy, radial radiation therapy, biological therapy, immunotherapy, or treatment with herb product within 4 weeks prior to initial treatment of this study. TSH suppression therapy is not included * Patients receive palliative irradiation for the bone metastasis within 2 weeks prior to before initial treatment of this study * Patients receive cytochrome P450 3A4 (CYP3A4) strong inducer or inhibitors (as seen in attachment 3) within 2 weeks (3 weeks for Hypericum perforatum) prior to initial treatment of this study * Clinically significant and active infection, including but not limited to HIV infection * Clinically significant history of liver disease, including virus hepatitis \[known HBV carrier, active hepatitis B virus (HBV) infection (>1\*104/ml) must be excluded; known hepatitis C virus (HCV) carrier, active HCV infection (>1\*103/ml) must be excluded\] and other hepatitis, cirrhosis * Major surgery within 4 weeks prior to enrollment, or the incision is still not fully healed * Subjects with known brain metastases or spinal cord compression who have not completed radiosurgery or surgical resection, or who have previously treated but with no clinical imaging evidence of disease stability * Subjects has not recovered from any toxicity related to previous anticancer treatment to level 0 or 1 (alopecia excluded) * Subjects who have received any investigational agent within 4 weeks prior to the first dose of study drug * Pregnancy (test is positive before the first dose of study drug) or any other lactating women * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

Study Objectives To compare treatment with oxaliplatin/5-FU/leucovorin plus vatalanib versus oxaliplatin/5-FU/leucovorin plus placebo in patients with colorectal cancer that has spread to other organs and are seeking first chemotherapy treatment Conditions: Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms Intervention / Treatment: DRUG: Vatalanib Location: Hungary, Canada, Portugal, United States, Taiwan, Czechia, France, Italy, Netherlands, United Kingdom, Spain, Brazil, Belgium, Sweden, Germany, New Zealand, Switzerland, Australia, Slovakia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion criteria: * Patients with metastatic colorectal cancer coming for initial chemotherapy * Documented metastatic colorectal cancer * WHO Performance Status of 0, 1, or 2 * Measurable tumors * Adequate hematologic status, liver and kidney function * Life expectancy greater than 12 weeks * Written informed consent obtained Exclusion criteria: * History or presence of central nervous system disease * Patients with a history of another primary cancer within 5 years * Prior chemotherapy for metastatic colorectal cancer * Prior full field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks before entry to study * Major surgery within 4 weeks or minor surgery within 2 weeks before entry to study * Investigational drugs within 4 weeks before entry to study * Prior therapy with anti-VEGF agents * Any prior therapy with oxaliplatin or allergy to platinum-containing drugs * Peripheral neuropathy with functional impairment * Female patients who are pregnant or breast feeding * Any severe or uncontrolled medical conditions which could prevent participation in study * Patients who are taking Coumadin Other protocol-defined inclusion / exclusion criteria may apply

Study Objectives The aim of the study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines and Cyclophosphamide can induce a measurable immune response in patients with metastatic malignant melanoma, and to evaluate the clinical effect (objective response rate) of the vaccination regime. Conditions: Advanced Melanoma Intervention / Treatment: BIOLOGICAL: tumor antigen loaded autologous dendritic cells Location: Denmark 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 proven progressive metastatic or locally advanced melanoma * No standard treatment indicated * Age: > 18 * WHO-Performance Status 0-1 * At least tone measurable tumor lesions according to the RECIST criteria. * Life expectancy more than 3 months * Acceptable CBC and blood chemistry results * Written informed consent Exclusion Criteria: * Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin). * Patients with metastatic disease in the central nervous system (CNS). * Patients with other significant illness including severe allergy, asthma, angina pectoris or congestive heart failure. * Patients with acute or chronic infection including HIV, hepatitis and tuberculosis. * Patients who are pregnant. * Patients who have received antineoplastic therapy including chemotherapy or immunotherapy less than 4 weeks before beginning the trial. * Patients who receive corticosteroids or other immunosuppressive agents. * Baseline serum LDH greater than 2.5 times the upper limit of normal. * Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis.

Study Objectives This is an open-label multicenter, study to assess the pharmacokinetic interaction of ketoconazole with ABT-199 in up to 12 subjects with relapsed or refractory non-Hodgkin's lymphoma. Conditions: Non-Hodgkin's Lymphoma Intervention / Treatment: DRUG: ABT-199, DRUG: Ketoconazole Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Subject must have relapsed or refractory non-Hodgkin's lymphoma. * Subject must have histologically documented diagnosis of non-Hodgkin's lymphoma as defined by a B-cell neoplasm in the World Health Organization (WHO) classification scheme except as noted in the exclusion criteria. * Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2. * Subject must have adequate bone marrow (independent of growth factor support per local laboratory reference range), coagulation, renal and hepatic function: * Absolute Neutrophil Count (ANC) greater than or equal to 1000/µL (without growth factor support unless neutropenia is clearly due to underlying disease); * Platelets greater than or equal to 75,000/mm3 (unless thrombocytopenia is clearly due to disease-related immune thrombocytopenia or to underlying disease; entry platelet count must be independent of transfusion within 14 days of Screening); * Hemoglobin greater than or equal to 9.0 g/dL (unless anemia is clearly due to underlying disease; entry hemoglobin must be independent of transfusion within 14 days of Screening); * If cytopenias are present, no evidence of myelodysplastic syndrome or hypoplastic bone marrow; * Subject must have activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × the upper normal limit (ULN); * Calculated creatinine clearance greater than or equal to 50 mL/min using a 24-hour urine collection for creatinine clearance or per the Cockcroft-Gault equation; * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3.0 × ULN of institution's normal range; * Bilirubin less than or equal to 1.5 × ULN. Subjects with Gilbert's Syndrome may have a bilirubin greater than 1.5 × ULN per discussion with the AbbVie medical monitor. Exclusion Criteria: * Subject has been diagnosed with Post-Transplant Lymphoproliferative Disease (PTLD), Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or mantle cell lymphoma (MCL). * Subject is receiving combination anti-retroviral therapy for HIV (due to potential drug-drug interactions between anti-retroviral medications and ABT-199, as well as anticipated ABT-199 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections). * Subject has hypersensitivity to ketoconazole. * Subject has a cardiovascular disability status of New York Heart Association Class greater than or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain. * Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease within the past 6 months that in the opinion of the investigator would adversely affect his/her participating in this study. * Subject has malabsorption syndrome or other condition which precludes enteral route of administration (e.g., prior surgical resection). * Subject has undergone an allogeneic stem cell transplant.

Study Objectives The primary purpose of this study is to assess the safety and tolerability of ascending single oral doses of PRA-027 in healthy Japanese females. The secondary purpose is to provide the initial pharmacokinetic and pharmacodynamic profiles of PRA-027 in healthy Japanese female subjects. Conditions: Uterine Leiomyomata (Fibroids) Intervention / Treatment: DRUG: PRA-027 Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

INCLUSION CRITERIA * Women of nonchildbearing potential aged 20 to 64 years. Must have a negative pregnancy test result within 48 hours before administration of test article. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound scan. * Body mass index (BMI) in the range of 17.6 to 26.4 kg/m2 and body weight must be at least 45 kg. * Healthy as determined by the investigator on the basis of screening evaluation. EXCLUSION CRITERIA * Any significant cardiovascular, hepatic, renal, respiratory, gynecologic gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease. * Any history of drug abuse or admitted alcohol abuse or history of alcohol use that may interfere with the subject's ability to comply with the protocol requirements. * Use of any investigational drug within 90 days before study day 1, use of any prescription drug within 30 days before study day 1, consumption of any caffeine-containing products (eg, coffee, tea, chocolate, or cola) or alcoholic beverages within 48 hours before study day 1, consumption of grapefruit or grapefruit-containing products within 72 hours before study day 1, use of any over-the-counter drugs, including herbal supplements (except for the occasional use of vitamins ≤100% of the recommended daily allowance), within 14 days before study day 1, or the donation of blood within 90 days before study day 1.

Study Objectives Subjects will receive treatment with nivolumab monotherapy at 240mg flat dose as a 30 minute IV infusion on Day 1 of a treatment cycle every 2 weeks (14 days) until confirmed progression of disease, unacceptable toxicity, death or withdrawal of consent. This study is designed to better evaluate the safety profile of nivolumab in a large series of patients with Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck. The primary endpoint of this study is the incidence of high-grade (CTCAE v 4.03 Grade 3 or higher), treatment-related, select adverse events. Conditions: Squamous Cell Carcinoma of Head and Neck Intervention / Treatment: DRUG: Nivolumab 240 MG in 24 ML Injection Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed Written Informed Consent; * Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study * Males and Females, 18 years of age; * Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx) not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy), p16 positive SCCHN of unknown primary; * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; * Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie, with radiation after surgery), primary (ie, with radiation or prior to it or to surgery as induction chemotherapy), recurrent, or metastatic setting; * Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria. * Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of oropharyngeal cancer * Tumor tissue (archival or fresh biopsy specimen) must be available; * Patients with CNS metastases: * Patients are eligible if CNS metastases are treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, patients must be either off corticosteroids or on a stable or decreasing dose ≤ 10 mg daily prednisone (or equivalent) OR * Patients are eligible if they have previously untreated CNS metastases and are neurologically asymptomatic. In addition, patients must be either off corticosteroids or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent); * Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration; * Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test; * Screening laboratory values must meet the following criteria (using CTCAE v4.03) and should be obtained within 14 days prior to the initial administration of study drug: * WBC ≥ 2000/μL * Neutrophils ≥1500/μL * Platelets ≥100 x103/μL * Hemoglobin ≥ 9.0 g/dL * Serum creatinine ≤ 1.5 x ULN o AST/ALT ≤ 3 x ULN * Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL). * Calcium levels must be normalized and maintained within normal limits for study entry and on treatment. Medical management of calcium levels is permitted. Note: Normal calcium levels may be based on ionized calcium or adjusted for albumin. * Subjects with an initial magnesium < 0.5 mmol/L (1.2 mg/dL) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at the investigator's discretion. * Women must not be breastfeeding. * WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post treatment completion; * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 halflives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 31 weeks post treatment completion. Exclusion Criteria: * Patients with untreated, symptomatic CNS metastases are excluded; * Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, p16 negative squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg, mucosal melanoma) are not allowed; * Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results; * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; * 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 prostate, cervix, or breast; * Subjects with active, known or suspected autoimmune disease. Subjects with experienced GVH disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition or previous neck RT only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Subjects with 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; * All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enroll. * Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Subjects who test positive for HCV antibody but negative for HCV ribonucleic acid are permitted to enroll; * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS); * Any Grade 4 laboratory abnormalities; * History of allergy to study drug components; * History of severe hypersensitivity reaction to any monoclonal antibody; * Prisoners or subjects who are involuntarily incarcerated. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study Objectives This study was performed to determine whether calcitriol provides a therapeutic advantage to alfacalcidol for treatment of secondary hyperparathyroidism in ESRD patients. Conditions: Secondary Hyperparathyroidism, End Stage Renal Disease Intervention / Treatment: DRUG: alfacalcidol and calcitriol Location: Thailand Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: SINGLE

Inclusion Criteria: * Chronic hemodialysis patients who underwent scheduled hemodialysis for at least 3 months with secondary hyperparathyroidism (intact PTH levels > 300 pg/mL) Exclusion Criteria: * (1) age < 18 years (2) hypersensitivity to calcitriol or alfacalcidol (3) inadequate dialysis \[defined as single-pooled Kt/V (sp-Kt/V) <1.2 and <2.0 for thrice a week and twice a week hemodialysis\] (4) corrected serum calcium >10.2 mg/dL or serum phosphate >6 mg/dL after adjusting dialysate calcium and phosphate binders (5) diameter of parathyroid gland >10 mm (6) pregnancy or lactation (7) liver cirrhosis (8) active kidney transplantation (9) previous parathyroidectomy (10) malignancy or chronic infection/inflammation.

Study Objectives Study objectives: To determine Ro resection rate of Docetaxel, cisplatin and fluorouracil combination for the treatment of neoadjuvant gastric carcinoma. Conditions: Stomach Neoplasms Intervention / Treatment: DRUG: Docetaxel, DRUG: Cisplatin, DRUG: Fluorouracil Location: Turkey Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically proven gastric adenocarcinoma diagnosis * Selected Stage IIB (T3N0M0), Stage IIIA (T2aN2M0, T2bN2M0, T3N1M0, T4N0M0), Stage IIIB (T3N2M0) and selected Stage IV (all T4 , NM0, all TN3M0's). Clinical staging performed with endoscopic ultrasound and CT. Laparotomy or laparoscopy is preferred to determine resectability and peritoneal involvement. * ECOG performance status between 0 and 2 * Acceptable hematological profile : * WBC (White Blood Cell) count ≥4000/mm3 * Platelet count ≥100 000 mm3 * Hemoglobin ≥9 g/100 mL (if lower, may be included following transfusion) * Adequate renal function * Serum creatinine <1.2 mg/dl or calculated creatinine clearance in 24-hours urine >60 mL/min. * Adequate hepatic function * Bilirubin < UNL * Transaminases (ALT, AST) <2.5 x UNL * Alcaline phosphatase <2.5 x UNL * Adequate pulmonary function * Adequate cardiac function * No prior chemotherapy for gastric cancer Exclusion Criteria: * Other histological types of gastric cancer (leiomyosarcoma, lymphoma) than adenocarcinoma * Pregnant or lactating patients * Patients with brain, bone or other metastases; peritoneal involvement * Other serious underlying medical conditions which could impair the ability of the patient to participate in the study (congestive heart failure, serious arrhythmia, uncontrolled diabetes mellitus, serious neuropathy), history of myocardial infarction within 6 months prior to study entry * Previous or other current malignancies, with the exception of carcinoma of the cervix uteri or breast cancer or basal cell skin cancer and a disease-free period shorter than 5 years * Active infection and other serious disease * Any other experimental drugs within a 4-week period prior to the study * Contraindications for the use of any study drug (e.g. history of hypersensitivity to the contents of the study drugs) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Objectives To evaluate the safety and efficacy of CD19/CD22 Bispecific chimeric antigen receptor (CAR)-T for the treatment of measurable residual disaese (MRD)-positive B cell acute lymphoblastic leukemia. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells. Conditions: MRD-positive, Acute Lymphoblastic Leukemia Intervention / Treatment: BIOLOGICAL: anti-CD19/CD22 CAR-T cells, DRUG: Fludarabine, DRUG: Cyclophosphamide Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * (1) CD19 positive/CD22 positive, or CD19-CD22 positive B-cell acute lymphoblastic leukemia; * (2)18 to 70 Years Old, Male and female; * (3) Expected survival > 12 weeks; * (4) ECOG score 0-2; * (5) Bone marrow examination clearly diagnosed as B-cell acute lymphoblastic leukemia and who met one of the following conditions: 1. Recurrent patients who achieves MRD-positive CR or CRi after standard therapy; 2. Those who achieves CR, but failed to achieve MRD-negative after at least 2 courses of consolidation therapy; 3. For Ph-positive ALL patients, a history of at least one TKI application is required in addition to two standard chemotherapy treatments * (6) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators; * (7) Liver, kidney and cardiopulmonary functions meet the following requirements: 1. Creatinine is in the normal range; 2. Left ventricular ejection fraction >50%; 3. Baseline oxygen saturation>92%; 4. Total bilirubin ≤ 2×ULN; 5. ALT and AST ≤ 2.5×ULN; * (8) Able to understand and sign the Informed Consent Document. Exclusion Criteria: * (1) Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection; * (2) Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive; * (3) Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; * (4) Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment; * (5) Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; * (6) Received CAR-T treatment or other gene therapies before enrollment; * (7) Patients with symptoms of central nervous system; * (8) Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion; * (9) The investigators consider other conditions unsuitable for enrollment.

Study Objectives This phase I trial studies the safety and best dose of ipilimumab, nivolumab, or both in combination with temozolomide in treating patients with newly diagnosed glioblastoma or gliosarcoma. Monoclonal antibodies, such as ipilimumab and nivolumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known which combination is a better treatment for glioblastoma or gliosarcoma. Conditions: Gliosarcoma, Supratentorial Glioblastoma Intervention / Treatment: BIOLOGICAL: Ipilimumab, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Nivolumab, DRUG: Temozolomide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report * The tumor must be unifocal, confined to the supratentorial compartment and have undergone a gross total or near gross total resection; this will increase the likelihood that the patient will not require corticosteroids or develop pseudoprogression * The formalin-fixed, paraffin-embedded (FFPE) tumor tissue block must be available to be sent for retrospective central pathology review after registration * Patients must be registered within 35 days of completion of chemoradiation * History/physical examination within 7 days prior to registration * Patients must have undergone an evaluation by magnetic resonance imaging (MRI) within 35 days of completing radiation and must also be within 7 days prior to registration; MRI must NOT demonstrate tumor progression, but patients with imaging changes consistent with pseudo-progression, stable neurologic function and not needing corticosteroid treatment are eligible * Karnofsky performance status >= 70 within 7 days prior to registration * Absolute neutrophil count >= 1,500 cells/mm\^3 * Platelet count >= 100,000 cells/mm\^3 * Hemoglobin (Hgb) > 9 g/dL (can be achieved with transfusion) * Blood urea nitrogen (BUN) =< 30 mg/dl * Serum creatinine =< 1.7 mg/dl * Total bilirubin (except patients with Gilbert's syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) =< 2.0 mg/dl * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) * The patient must have completed chemoradiation (all cohorts) within standards of care established by prior Radiation Therapy Oncology Group (RTOG)/Network Radiotherapy Group (NRG) Oncology studies as follows: * Radiation therapy * Modality: either 3-dimensional (3D) or intensity-modulated radiation therapy (IMRT), or proton therapy is allowed * Time to initiation: radiotherapy must be initiated within or equal to 42 days after surgery * Target volumes: target volume definition will be based upon postoperative-enhanced MRI; preoperative imaging should be used for correlation and improved identification, as necessary * Dose guidelines: the initial target volume will be treated to 46 Gray (Gy) in 23 fractions; after 46 Gy, the cone-down or boost volume will be treated to a total of 60 Gy, with seven additional fractions of 2 Gy each (14 Gy boost dose) * Temozolomide during concomitant radiation therapy * Temozolomide must have been administered continuously from day 1 of radiotherapy to the last day of radiation (+/- 3 days to take into consideration holidays) at a daily oral dose of 75 mg/m\^2 for a maximum of 49 days (except missed doses due to toxicity) * The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent * The patient must provide study-specific informed consent prior to study entry * Echocardiogram (ECHO) cardiogram and cardiology consultation required within 7 days prior to registration for patients with a history of congestive heart failure or cardiovascular disease or history of exposure to cardiotoxic agents who are not already excluded Exclusion Criteria: * Definitive clinical or radiologic evidence of progressive disease * Prior placement of Gliadel wafer or local brachytherapy * Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years * Unstable angina within the last 6 months prior to registration * Transmural myocardial infarction within the last 6 months prior to registration * Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 7 days prior to registration * New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration * History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration * Serious and inadequately controlled cardiac arrhythmia * Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for additional liver function tests and coagulation parameters are not required for entry into this protocol * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol * Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for immunologic toxicity * Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded * Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible * Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy * Pregnancy or lactating females; women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration * History of severe hypersensitivity reaction to any monoclonal antibody

Study Objectives The study will compare PK, efficacy, safety, and immunogenicity of SIBP-01 (Trastuzumab Biosimilar) in combination with Docetaxel and Carboplatin versus Herceptin® (CN-Trastuzumab) approved in the CN in combination with Docetaxel and Carboplatin in patients with operable HER2 positive, with early or locally advanced HER2-positive breast cancer. The hypothesis to be tested in this study is the tpCR of patients with Cycle 6 of SIBP-01 is similar to CN-approved trastuzumab, using a 90% bilateral confidence interval between 0.74 and 1.5. Conditions: HER2-positive Early Breast Cancer Intervention / Treatment: DRUG: SIBP-01, DRUG: Herceptin, DRUG: Docetaxel, DRUG: Carboplatin Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Those voluntarily signing the informed consent form, understanding the study and willing to follow all testing procedures; * Females aged ≥ 18 years and ≤ 75 years (at the date of signing the informed consent form); * Patients diagnosed with early (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0) invasive breast cancer histologically; * Patients with HER2-positive breast cancer: HER2 detection is based on the Chinese Breast Cancer HER2 Detection Guidelines (2019 Edition), the immunohistochemistry (IHC) method is used to detect the expression level of HER2 protein, and the in situ hybridization (ISH) method is used to detect the HER2 gene amplification level. ISH includes fluorescence in situ hybridization (FISH) and bright-field in situ hybridization. The common bright-field in situ hybridization method includes chromogenic in situ hybridization (CISH) and silver-enhanced in situ hybridization (SISH);The HER2-positive criterion is: IHC detection +++, or IHC++, and further in situ hybridization confirms that HER2 gene amplification is positive; * Those planning to receive final surgical resection of breast cancer, i.e. breast-conserving surgery or total mastectomy, sentinel node (SN) biopsy or axillary lymph node dissection (ALND); * Those planning to receive neoadjuvant chemotherapy; * Those with the maximum primary tumor diameter of > 2cm determined by the standard evaluation method of study center (MRI); * Patients with performance status score of 0 or 1 by the US Eastern Cooperative Oncology Group (ECOG); * Those with left ventricular ejection fraction (LVEF) of ≥ 55% within 4 weeks prior to randomized enrollment; 10) Those with suitable organs and hematopoietic functions, without significant abnormality in the following laboratory examinations: * Absolute neutrophil count (NEUT#) ≥1.5×109/L; * Absolute white blood cell count (WBC) ≥ 3.0 × 109/L; * Platelet ≥90×109/L; * Hemoglobin ≥90g/L; * Serum creatinine ≤1.5 x upper limit of normal (ULN); * AST and ALT values ≤ 1.5 x ULN; * Serum total bilirubin (TBIL) ≤ 1.5 x ULN; * International normalized ratio (INR) ≤ 1.5 x ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (except for subjects undergoing anticoagulation therapy). (The above laboratory examinations are subject to the normal values of each clinical research center) * Female patients without menopause or surgical sterilization: they agree to practice abstinence or effective contraception during treatment and at least 7 months after the last administration in the study treatment. Women at childbearing age who have undergone surgical sterilization (including hysterectomy, bilateral oophorectomy or total hysterectomy) or have been menopausal (defined as having no menstruation for more than 12 months without medical reason) are considered as having no possibility of pregnancy. Throughout the clinical trial, women with the possibility of pregnancy are willing to practice medically accepted, effective contraception, including intrauterine contraceptive device. Exclusion Criteria: * Pregnant or lactating women, and patients with positive baseline pregnancy test; women of childbearing age who do not agree to practice abstinence or effective contraception during the study period and within 7 months after the last administration; * Those with a clear history of drug allergy, especially those with prior severe allergic reaction to macromolecular protein preparation/monoclonal antibody, or to any of the test drug components (NCI-CTCAE 5.0 greater than grade 3); * Patients with bilateral breast cancer or inflammatory breast cancer; * Patients with (metastatic) breast cancer Stage IV; * Those with a history of congestive heart failure, unstable angina, arrhythmia or myocardial infarction; * Those with other invasive tumors (including second primary breast cancer) that might affect the result evaluation and protocol compliance; however, subjects who are cured with a disease-free survival of at least 5 years may be enrolled; * Patients with breast cancer who have previously received chemotherapy, endocrine therapy, or anti-HER2 biotherapy, or have received breast surgery (except for diagnostic biopsy of primary breast cancer); * Those with known, uncontrolled, active bacterial, viral, fungal, mycobacterial, parasitic or other infections (excluding nail bed fungal infection) or with any significant systemic infection event that required intravenous antibiotic treatment or hospitalization (except for neoplastic fever) within 4 weeks prior to enrollment); * Those with any positive HIV antibody or treponema pallidum antibody; * Those with active hepatitis B (hepatitis B virus DNA titer is above the lower limit of normal); * Those with existing, sudden lung disease, interstitial lung disease, pneumonia or pulmonary fibrosis, except for local interstitial pneumonia induced by radiotherapy; * Those with a prior history of drug abuse, alcohol abuse or drug addiction; * Those with a clear history of neurological or mental disease and with poor compliance, such as epilepsy and dementia; * Those with a major surgical operation or infusion of blood or blood components 4 weeks prior to the clinical trial; * Those with blood loss or donation of more than 400 ml within the 2 months prior to the clinical trial; * Those who have participated in other clinical trials 3 months prior to this clinical trial; * Those with reduced possibility of enrollment (e.g. weakness) or non-compliance tendency during the study period, or with other diseases that might complicate enrollment as judged by the investigator.

Study Objectives The purpose of this study is to evaluate the safety and tolerability of XL147 in subjects with solid tumors or lymphoma. Both a capsule and a tablet formulation will be evaluated. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells. Conditions: Cancer, Lymphoma Intervention / Treatment: DRUG: XL147 (SAR245408), DRUG: XL147 (SAR245408) 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: * The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival. An expanded cohort will be enrolled; NSCLC subjects enrolled must have a diagnosis of relapsed or refractory NSCLC (Stage IIIB or IV) and have received at least two prior regimens including one platinum-based chemotherapy regimen. * The subject has a histologically confirmed diagnosis of lymphoma which is relapsed or refractory to standard therapy. * For subjects with solid tumors, the subject has disease that is assessable by tumor marker, physical, or radiologic means. There are separate criteria that apply to subjects with lymphoma. * Subjects with indolent lymphoma must have documented disease status within 12 months prior to study entry. * The subject is ≥18 years old. * The subject's weight is ≥40 kg. * The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2. * The subject has adequate organ and marrow function, and a fasting plasma glucose (FPG) <160 mg/dL and HbA1c of <8% at screening. * For the subjects with solid tumors who are to be enrolled into the expanded MTD cohort and tumor genetic alteration subjects: 1. tumor tissue amenable to serial biopsy, and 2. additional informed consent. * The subject is capable of understanding and complying with the protocol and has signed the informed consent document. * Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study and for 3 months following discontinuation of study drug. * Female subjects of childbearing potential must have a negative serum pregnancy test at screening. * At least ten 4-10 micron tissue sections, archival or fresh, or a tissue block, of the subject's tumor should be identified and designated for shipment to the sponsor where allowed by local regulatory bodies. For subjects with lymphoma, tissue from an excisional or core biopsy or, in case of marrow involvement, a bone marrow aspirate/biopsy is acceptable. Exclusion Criteria: * The subject has previously been treated with a selective PI3K inhibitor. * Additional restrictions on prior treatment apply. * For lymphoma subjects: known central nervous system involvement, autoimmune disease requiring immunosuppressive therapy, systemic treatment with prednisone >20mg/day or equivalent within 2 weeks prior to first dose of XL147, autologous stem cell transplantation within 12 weeks prior to first dose, history of any allogeneic transplantation. * The subject has not recovered from toxicity due to all prior therapies. * The subject has a primary brain tumor. Subjects with brain metastasis are considered eligible if the subject has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks. * The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin is permitted). * The subject has prothrombin time/partial thromboplastin time (PT/PTT) or International Normalized Ratio (INR) test results at screening that are above 1.3x the laboratory upper limit of normal. * The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. * The subject has psychiatric illness/social situation(s) that would limit compliance with study requirements. * The subject is pregnant or breastfeeding. * The subject is known to be positive for the human immunodeficiency virus (HIV). * The subject has a previously identified allergy or hypersensitivity to components of the XL147 formulation. * The subject has a baseline corrected QT interval (QTc) >460 ms. * The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Study Objectives Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week. It will be the first time this agent will be administered to humans. At lower dose levels, the first cycle duration is 7 weeks. In subsequent cycles, APO010 is administered as 4 weekly doses followed by a two-week drug rest, cycle duration is 6 weeks. Based on preclinical studies of APO010 may cause liver toxicity and a drop in platelets, that recover within 5 days. The main aim of the study is to identify the recommended dose of APO010 for future clinical studies of APO010. Conditions: Cancer Intervention / Treatment: DRUG: APO010 Location: Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological/cytological diagnosis of non-resectable solid tumors for which therapy of proven efficacy does not exist or is no longer effective. * Eastern Cooperative Oncology Group (ECOG) performance status ≤1. * Ongoing toxicity associated with prior anticancer therapy ≤Grade 1 (NCI-CTCAE v.3.0). * No more than 3 prior chemotherapy lines for advanced disease (not including neo/adjuvant chemotherapy; reintroduced chemotherapy is considered only 1 line, e.g. platinum reintroduction in ovarian cancer). Exceptions must to be discussed with, and agreed by the Co-ordinating Investigator. * Adequate hematological, liver and renal function, e.g.: * Hemoglobin ≥9 mg/dl; Absolute Neutrophil Count (ANC) ≥1.5x109/l; platelets ≥100x109/l; normal coagulation factors (INR, PTT, PT). * Serum bilirubin ≤upper normal limit (UNL); ALT, AST ≤ UNL but ≤ 2.5 x UNL in case of liver metastases; alkaline phosphatase (liver isoenzyme fraction) ≤ UNL or ≤1.5 x UNL of in case liver metastases; albumin within normal limits. * Creatinine ≤1.5 mg/dl (≤133µmole/l) or calculated creatinine clearance ≥60 ml/min. * Life expectancy of at least 3 months. * Capability of understanding the nature of the trial and giving written informed consent. Exclusion Criteria: * Less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than 2 weeks since last hormone or immunotherapy or signal transduction therapy. * More than 30% liver parenchyma involvement assessed by computed tomography (CT) scan. * History of hypersensitivity to preparations containing human albumin, and to intravenously administered proteins/peptides/antibodies. * Active infection. * Presence of cirrhosis with abnormal liver function test or chronic viral hepatitis. * Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder. * Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study. * Symptomatic brain metastases, primary brain tumors or leptomeningeal disease. * Pregnancy or lactation, or unwillingness to use adequate method of birth control

Study Objectives RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving bortezomib as maintenance therapy after autologous stem cell transplantation may kill more cancer cells and prolong remission. PURPOSE: This phase I/II trial is studying the side effects and best dose of adjuvant bortezomib as maintenance therapy and to see how well it works in treating patients who have undergone stem cell transplantation for intermediate or advanced multiple myeloma. Conditions: Multiple Myeloma and Plasma Cell Neoplasm Intervention / Treatment: DRUG: bortezomib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of intermediate or advanced multiple myeloma meeting criteria for at least 1 2 following: * Intermediate- to high-M-component production rates (immunoglobulin \[Ig\]G > 5 g/dL or immunoglobulin A (IgA) > 3 g/dL or urine M component > 4 g/24 hours) * More than one osteolytic bone lesion or radiographic evidence of diffuse osteoporosis * β-2 microglobulin > 3 * Nonsecretory myeloma if bone marrow plasmacytosis is greater than 30% * Must have undergone autologous peripheral blood stem cell transplantation within the past 3-4 months * Age 18 to 69 years old * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 30,000/mm\^3 * serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) ≤ 300 IU * Bilirubin ≤ 2 mg/dL * Creatinine ≤ 2.0 mg/dL * Creatinine clearance ≥ 30 mL/min * Negative pregnancy test * Fertile patients must use effective contraception Exclusion Criteria: * concurrent major cardiac disease that would preclude study participation * concurrent major pulmonary disease that would preclude study participation * pregnant or nursing * peripheral neuropathy ≥ grade 2 * history of hypersensitivity to bortezomib, boron, or mannitol * concurrent major gastrointestinal or bladder disease that would preclude study participation * concurrent major neurologic or psychiatric disease that would preclude study participation * dementia or significantly altered mental status that would preclude giving informed consent * prior interferon post-transplantation * prior thalidomide post-transplantation * prior chemotherapy post-transplantation * prior radiotherapy post-transplantation * prior investigational therapy post-transplantation * prior bortezomib * prior therapy for myeloma post-transplantation * other concurrent anti-myeloma therapy * other concurrent investigational therapy

Study Objectives A multicenter randomized phase II study evaluating the activity and tolerability of three different combinations of docetaxel (taxotere) and irinotecan (campto) as second line therapy for recurrent or metastatic non small cell lung cancer (NSCLC) Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Irinotecan, DRUG: Docetaxel Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically proven NSCLC * Recurrent or metastatic NCSLC Exclusion Criteria: * Prior malignancies; except for cured non melanoma skin cancer, curatively treated in situ carcinoma of the cervix or other cancer adequately treated an with non evidence of disease for at least 5 years * History or presence of brain or meningeal metastases

Study Objectives This phase I/II trial studies the side effects and best dose of carfilzomib when given together with melphalan and to see how well they work in treating patients with multiple myeloma before stem cell transplant. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving carfilzomib together with melphalan may kill more cancer cells. Conditions: DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma Intervention / Treatment: PROCEDURE: Autologous Bone Marrow Transplantation, PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, DRUG: Carfilzomib, OTHER: Laboratory Biomarker Analysis, DRUG: Melphalan Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Serum creatinine =< 2 mg/dL * Absolute neutrophil count >= 1000/uL * Platelet count >= 50,000/uL * Hemoglobin >= 8.0 g/dL * Diagnosis of symptomatic MM * Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following: * Serum monoclonal protein >= 1.0 g/dL * >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis * Serum immunoglobulin free light chain >=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio * Bone marrow plasma cells >= 30% * NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis * NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapy * Patient is considered for autologous stem cell transplantation with full dose melphalan (200 mg/m\^2) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 * Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity) * Provide informed written consent * Ejection fraction >= 45% * Corrected pulmonary diffusion capacity of greater than or equal to 50% * Forced expiratory volume in 1 second (FEV1) >= 50% * Forced vital capacity (FVC) >= 50% * Negative pregnancy test performed =< 7 days prior to registration, for women of childbearing potential only * Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida for treatment * Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up * Willing to provide blood and bone marrow samples for correlative research purposes Exclusion Criteria: * Prior autologous or allogeneic bone marrow/peripheral blood stem cell transplant * More than two prior regimens for therapy of MM * Myocardial infarction within 6 months prior to enrollment, or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant * Seroreactivity for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) I or II, hepatitis B virus (HBV), hepatitis C virus (HCV) * Other active malignancy < 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer * Any of the following: * Pregnant women or women of reproductive capability who are unwilling to use effective contraception * Nursing women * Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment * Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease * Concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment * Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments

Study Objectives Postoperative pain caused by surgery-associated tissue injury is a major concern for all the clinical practitioners. Because it affects multiple systems and induces physiological, immunological and psychological changes. Previous literature showed surgical injury induces a systemic inflammatory metabolic-endocrine response that is proportional to the severity of the surgical stress. In surgeries such as liver transplantation, the patients suffer not only from postoperative pain but also an additional oxidative stress caused by ischemia reperfusion. Previous report have proved that an adequate postoperative pain control improves the recovery and reduces the inflammatory cascade by suppression of physiological and psychological stresses. However, the effect of postoperative pain management on ischemia reperfusion injury is unclear so far. In this three year study, we plan to continue our previous study to test the following two hypothesis: (1) postoperative pain exacerbate remote organ injury caused by ischemia reperfusion, (2) the interaction of different antinociceptive modalities on ischemia reperfusion injury. Conditions: End Stage Liver Disease, Lung Cancer Intervention / Treatment: DRUG: Patient controlled analgesia Location: Taiwan Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * End stage liver disease patients scheduled for liver transplantation in National Taiwan University Hospital * Lung cancer patients scheduled for thoracic surgery in National Taiwan University Hospital Exclusion Criteria: * preoperative pulmonary dysfunction

Study Objectives This study investigates the safety and efficacy of the combination therapy with BAY86-9766 and sorafenib in patients with liver cancer. Safety will be determined by laboratory and other evaluations. Efficacy of the combination BAY86-9766 and sorafenib will be determined by disease control rate, overall survival, time to progression, response rate and duration of response. Conditions: Carcinoma, Hepatocellular Intervention / Treatment: DRUG: BAY86-9766 MEK Inhibitor + Sorafenib Location: Singapore, Korea, Republic of, Taiwan, Hong Kong 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 age >= 18 years of age * Life expectancy >= 12 weeks * Histologically or cytologically confirmed diagnosis of HCC, unresectable advanced or metastatic * Liver function status of Child-Pugh class A. Child-Pugh status based on clinical findings and laboratory results during the screening period * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 * Patients must have at least one naïve (not previously treated by locoregional therapy) uni-dimensional measurable lesion by CT or MRI according to RECIST 1.1 * Adequate bone marrow, liver and renal function Exclusion Criteria: * Previous or concurrent cancer other than HCC, except for cervical carcinoma in situ, basal cell carcinoma, superficial bladder tumors. * History of cardiac disease: Congestive heart failure (CHF), unstable angina, arrhythmias, Uncontrolled hypertension * Clinically significant GI bleeding (CTCAE grade 3 or higher) within 30 days * Renal failure requiring hemo- or peritoneal dialysis * Known human immunodeficiency virus (HIV) infection * Known history or symptomatic metastatic brain or meningeal tumors * History of organ allograft. * History of interstitial lung disease (ILD). * Excluded previous therapies and medications: * Prior use of systemic anti-cancer treatment for HCC including cytotoxic chemotherapy, targeted agents, or any experimental therapy * Radiotherapy within 4 weeks prior to start of study treatment * Any other investigational agents within 4 weeks from the first dose of study treatment * Major surgery within 4 weeks of start of study * Concomitant use of strong inhibitors and strong inducers of CYP3A4

Study Objectives This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve and die. Conditions: Mesothelioma Intervention / Treatment: DRUG: ADI-PEG 20 plus Pem Platinum, OTHER: Placebo plus Pem Platinum Location: Italy, United Kingdom, United States, Australia, Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Histologically proven unresectable MPM of biphasic or sarcomatoid histology * Naïve to chemotherapy or immunotherapy * ECOG PS 0-1 * Expected survival of at least 3 months * Age 18 years or over (there is no upper age limit) * Measurable disease by modified RECIST criteria for MPM for local pleural disease and RECIST 1.1 criteria for metastatic lesions * Written (signed and dated) informed consent and must be capable of co-operating with treatment and follow up * Adequate hematologic, hepatic, and renal function Exclusion Criteria: * Radiotherapy (except for palliative reasons) in the previous two weeks before study treatment * History of unstable cardiac disease * Ongoing toxic manifestations of previous treatments * Symptomatic brain or spinal cord metastases (patients must be stable for > 1 month post radiotherapy or surgery) * Major thoracic or abdominal surgery from which the patient has not yet recovered.

Study Objectives The purpose of this study is to evaluate the efficacy and tolerability of the ECF regimen (epirubicin, cisplatin and FU) combined with endostar-- a inhibitor of angiogenesis, in patients with advanced or metastatic gastric cancer (A/MGC). Conditions: Gastric Cancer Intervention / Treatment: DRUG: ECF-endostar Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed advanced or metastatic adenocarcinoma of the stomach * ECOG performance scale ≤ 2 * At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan) * Adequate hepatic, renal, heart, and hematologic functions (platelets>80×109/L, neutrophil> 2.0 × 109/L, serum creatinine ≤ 1.5mg/dl, total bilirubin within upper limit of normal(ULN), and serum transaminase ≤ 2.5×the ULN) Exclusion Criteria: * Pregnant or lactating women * Concurrent cancer * History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix * Neuropathy, brain, or leptomeningeal involvement * Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months or high risk/uncontrolled arrhythmia * Uncontrolled significant comorbid conditions and previous radiotherapy

Study Objectives The purpose of this study is to estimate antitumour activity of abiraterone acetate in Patients with a Molecular Apocrine HER2-negative locally advanced or metastatic Breast Cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: Abiraterone Acetate Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Women aged ≥18 years; * Histologically confirmed locally advanced or metastatic breast cancer; * Triple negative breast cancer: Estrogen receptor (ER)-negative and Progesterone receptor (PR)-negative, as defined by a <10 % tumour stained cells by immunohistochemistry (IHC); HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative), confirmed centrally before inclusion with FFPE tissue from either primary or metastatic breast cancer site\*; * Androgen receptor (AR)-positive, as defined centrally by a ≥10% tumour stained cells by IHC (AR assessment by local pathologist before inclusion is not mandatory); * Patients could be chemotherapy naïve (provided they are not presenting with life-threatening metastasis) or have received any number of previous lines of chemotherapy (providing their life expectancy is ≥3 months); * Pre and post menopausal patients are eligible. * Measurable or non measurable disease according to RECIST v1.1 criteria; * PS (ECOG) ≤2; * Normal haematological function: ANC ≥1,500/mm3; platelets count ≥100,000/mm3; haemoglobin >10 g/dl; * Normal hepatic function: total bilirubin ≤1.5 upper normal limit (UNL); ASAT and ALAT ≤2.5 UNL (≤5 UNL in the presence of liver metastases); * Creatinine clearance (MDRD formula) ≥50 mL/min OR creatinine ≤1.5 times ULN; * Normal kalemia (serum potassium ≥3.5 mM), natremia and magnesemia; * Systolic blood pressure (BP) <160 mm Hg and diastolic BP <95 mm Hg, as documented on inclusion day (Hypertension at baseline assessment allowed provided it is currently controlled under anti-hypertensive drugs); * Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before inclusion; * If receiving a bisphosphonate or denosumab, dose must have been stable for at least 2 doses before inclusion; * Patient agreeing to use effective contraception during and for ≥ 6 months after completion of study treatment; * Patient able to comply with the protocol; * Patient must have signed a written informed consent form prior to any study specific procedures; * Patient must be affiliated to a Social Health Insurance. Exclusion Criteria: * Male breast cancer; * HER2-positive status (positivity defined as IHC3+ and/or FISH amplification >2.2); * Other concurrent malignancies, except adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin; patients who have undergone potentially curative therapy for a prior malignancy are eligible provided there is no evidence of disease for ≥ 5 years and patient is deemed to be at low risk for recurrence; * Active brain metastases or leptomeningeal disease; History of brain metastases allowed provided lesions are stable for at least 3 months as documented by head CT scan or MRI of the brain; * Non-malignant systemic disease, including active infection or concurrent serious illness that would make the patient a high medical risk; * Significant cardiovascular disease, including any of the following: 1. NYHA class III-IV congestive heart failure; 2. Unstable angina pectoris or myocardial infarction within the past 6 months; 3. Severe valvular heart disease; 4. Ventricular arrhythmia requiring treatment. * Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not be included; * Patients with known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisone, or their excipients; * Persistent toxicities ≥ grade 2 from any cause, except chemotherapy-induced alopecia and Grade 2 peripheral neuropathy; * Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy; * Any gastrointestinal disorder interfering with absorption of the study drug; * Difficulties with swallowing study capsules; * Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (CT) within the last 3 weeks (2 weeks for oral or weekly CT ; 6 weeks for nitrosoureas and mitomycin C), or other investigational agents ; Concurrent palliative radiotherapy allowed; * Concurrent enrolment in another clinical trial in which investigational therapies are administered; * Pregnant women, women who are likely to become pregnant or are breast-feeding; * Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial; * Patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol; * Individual deprived of liberty or placed under the authority of a tutor.

Study Objectives This is a randomized Phase I/II study designed to assess the induction of an anti-tumor immune response; the effect of cyclophosphamide on the vaccine; and to assess safety in subjects with advanced ovarian cancer or primary serous peritoneal cancer given a multivalent DC vaccine, with or without a single dose of cyclophosphamide. Potential benefit may range from no direct benefit to the study participants to stimulation of the subject's own immune system to attack ovarian cancer to prevent relapse. Conditions: Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma Intervention / Treatment: BIOLOGICAL: DC-Ova, BIOLOGICAL: DC Ova with Cyclophosphamide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * The following conditions must be met before a patient may be enrolled in the study. * Patients age 18 years of age and older. Disease Criteria. Patients will be eligible: * If no clinical evidence of disease is present after diagnosis with stage III or * IV disease and completion of primary surgery and chemotherapy, or, if no clinical evidence of disease is present after completion of chemotherapy for a disease recurrence diagnosed after a progression-free interval of at least 2 years, for patients of any initial stage.or primary peritoneal carcinoma. * Complete clinical response = no evidence of tumor lesions shown by abdominal CT scan or MRI, chest Xray,and CA 125 level ≤ 35 UI/mL. * Time from completion of Chemotherapy will be no more than 6 months from last dose from initial diagnoses. * HLA-A2 positive (must be typed by molecular methods; all A2 alleles eligible). Patients with adequate organ function as measured by: * Hematopoietic: WBC at least 3000/mm3; platelets at least 100,000/mm3, hemoglobin at least 10.0 g/dL (may be transfused). * Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be ≥50% or within the normal range of the institution. A cardiology clearance will be required for LV ejection fraction <50%. * Hepatic: SGOT within 2x normal range and total bilirubin ≤ 2.0 mg/dL. * Renal: Serum creatinine ≤2.0 mg/dL * Adequate performance status > 80% (Karnofsky) or ECOG 0-2 * Written informed consent conforming to institutional guidelines. * Life expectancy > 6 months and absence of co-existing medical problems which would preclude participation in the judgment of the principal investigator. Exclusion Criteria: * Any one of the following conditions eliminates a patient from participating in this protocol. * Prior malignancy (except basal cell or squamous cell skin cancer) within the past five years. * Presence of active Central Nervous System disease. * Serious systemic disease. * Active bacterial, viral or fungal infections. * Chemotherapy, biologic therapy or radiation therapy less than 4 weeks prior to study entry. * History of active autoimmunity or immunosuppression. * Use of immunosuppressive drugs within 4 weeks prior to study entry or anticipated use of immunosuppressive agents. * Patients with tumors of low malignant potential (borderline tumors) will not be eligible. * Seropositivity for HIV, HTLV-1, or HTLV-2. * Prior Influenza vaccination with the current vaccine will exclude patient from receiving protocol-specified influenza vaccine but will not exclude participation with the other aspects of the protocol. Each year's vaccine supply generally becomes available in October. Patients with a history of serious hypersensitivity to eggs, previous influenza vaccine or its components, will not receive influenza vaccine, but may continue to participate in other aspects of the protocol. Patients with a history of serious hypersensitivity to the Prevnar vaccine, its components, or diptheria toxoid will not receive the Prevnar vaccine, but may continue to participate in other aspects of the protocol. * Pregnant or breast feeding subjects.

Study Objectives This is an observational study in which data from the past of people with solid tumors harboring an NTRK gene fusion in Japan are studied. In observational studies, only observations are made without specified advice or interventions. Advanced or recurrent solid tumor harboring an NTRK gene fusion is a rare type of solid cancer caused by specific changes in the genes called NTRK gene fusion, and which has spread to nearby tissues and/or lymph nodes or has returned. Due to this change in the gene, an altered protein known as a TRK fusion protein is made, which can cause cancer cells to grow and survive. The main purpose of this study is to learn more about NTRK gene fusion in people in Japan. To do this, researchers will collect information on the number or percentage of Japanese people with NTRK gene fusion in any solid tumor. The data will come from the national database called C-CAT. They will cover the period from June 2019 until January 2023. Besides this data collection, no further tests or examinations are planned, and no visits are required in this study. Conditions: Advanced or Recurrent Solid Tumor Harboring an NTRK Gene Fusion Intervention / Treatment: OTHER: No Drug Location: Japan Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with any solid tumor and genome profiling results Exclusion Criteria: * None

Study Objectives The primary objective of this study is to determine whether the test product, mercaptopurine oral 100 mg/5 mL suspension, and the reference product, Purinethol® 50 mg tablets are bioequivalent. For this purpose the PK profile of 6-mercaptopurine (6-MP) will be compared after administration of a single dose of each of the two formulations, under fasting conditions. The secondary objective is to assess the safety and tolerability of the test product, mercaptopurine oral 100 mg/5 mL suspension. Conditions: Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: Mercaptopurine 20mg/ml oral suspension, DRUG: Mercaptopurine 50mg tablet Location: South Africa Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Healthy male subjects, 18 years to 50 years inclusive at time of last administration of the IMP. * Body Mass Index (BMI) between 18.5 and 30 kg/m2. * Body mass not less than 50 kg. * Medical history, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations: Findings clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the investigator considers the deviation to be irrelevant for the purpose of the study. * Non-smokers. Exclusion Criteria: * Current alcohol use > 21 units of alcohol per week for males. * Regular exposure to substances of abuse (other than alcohol) within the past year. * Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks prior to the first administration of IMP except if this will not affect the outcome of the study in the opinion of the investigator. * Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks before the first administration of IMP in this study. * Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system. * A major illness during the 3 months before commencement of the screening period. * Subjects with a deficient, low or intermediate TPMT enzyme activity by means of phenotyping. * Subjects who participated in previous azathioprine/mercaptopurine studies within six months will be excluded. * Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome. * Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of IMP. * Diagnosis of hypotension or hypertension made during the screening period or current diagnosis of hypertension. * Resting pulse of > 100 beats per minute or < 45 beats per minute during the screening period, either supine or standing. * Positive testing for HIV and/or Hepatitis B and/or Hepatitis C. * Positive urine screen for drugs of abuse. * Positive urine screen for tobacco use. * Subjects who plan to procreate within 12 weeks after IMP administration, or not willing to practice reliable forms of contraception during the study and for at least 12 weeks after the last dose of IMP. * Immunization using a live organism vaccine within 4 weeks prior to the first dosing of IMP. * Any specific IMP safety concern.

Study Objectives This study will evaluate GMI-1271, a specific E-selectin antagonist, in acute myeloid leukemia in combination with standard agents used to treat this disease. Conditions: Leukemia, Myeloid, Acute Intervention / Treatment: DRUG: GMI-1271, DRUG: Mitoxantrone, DRUG: Etoposide, DRUG: Cytarabine, DRUG: Idarubicin Location: United States, Ireland, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion criteria: * AML (including secondary AML) diagnosed as per WHO criteria * For relapsed/refractory subjects only: * Subjects age ≥ 18 years with relapsed or refractory AML after ≤ 2 prior induction regimens, at least one containing anthracyclines * Medically eligible to receive MEC * Absolute blast count (ABC) ≤ 40,000/mm * For treatment-naïve subjects only: * Subjects ≥ 60 years of age with newly diagnosed AML * Medically eligible to receive "7+3" cytarabine/idarubicin * ABC count ≤ 40,000/mm * ECOG performance status 0-2 * Hemodynamically stable and adequate organ function Exclusion criteria: * Acute promyelocytic leukemia * Acute leukemia of ambiguous lineage (biphenotypic leukemia) * Active signs or symptoms of CNS involvement by malignancy * No prior G-CSF, GM-CSF or plerixafor within 14 days of study drug dosing * Known history or evidence of active hepatitis A, B, or C or HIV * Uncontrolled acute life threatening bacterial, viral or fungal infection * Active graft versus host disease (GVHD) ≥ Grade 2 or extensive chronic GVHD requiring immunosuppressive therapy * Hematopoietic stem cell transplantation ≤ 4 months of dosing * Clinically significant cardiovascular disease

Study Objectives A prospective, double-blinded study. The present study consisted in applying Stroke volume variation fluid guided therapy to old patients (65 years old) undergoing radical resection of colon surgery. The aim of this study is to compare the effects of norepinephrine and phenylephrine in treating perioperative hypotension, and to find the safest and most effective vasopressor for elderly. Conditions: Hypotension, Fluid Therapy Intervention / Treatment: DRUG: phenylephrine, DRUG: Norepinephrine Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Operation time should be equal or greater than 2h, * Patients older than 65 years old, * ASA Ⅱ or Ⅲ. Exclusion Criteria: * Clear arrhythmia, * Need to apply PEEP, * Peripheral vascular disease and arterial catheter contraindications.

Study Objectives T-cell Non-Hodgkin's lymphomas are a group of cancers that are usually treated with chemotherapy, radiation therapy, or occasionally surgery. T-cell lymphomas are relatively uncommon and therefore not well studied. Treatment approaches are patterned after the more common B-cell lymphomas. T-cell lymphomas are more likely to relapse following standard therapy than are B-cell lymphomas. New therapies are needed for T-cell lymphomas. In this study, we will administer the drug called lenalidomide as a pill to patients with T-cell lymphoma. The goals are to determine if the drug can induce regression of the cancer, and to determine if the treatment is well tolerated in this patient group. This study will take place at six cancer centres across Canada. Conditions: T-cell Lymphoma Intervention / Treatment: DRUG: Lenalidomide Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * T-cell lymphoma (excluding mycosis fungoides) * WHO performance status 0-2 * measurable lesions * acceptable hematological and biochemical parameters * previously treated OR untreated but not suitable for standard therapy Exclusion Criteria: * pregnant * HIV * viral hepatitis