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Study Objectives Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as motexafin gadolinium may make the tumor cells more sensitive to radiation therapy. Phase I trial to study the effectiveness of motexafin gadolinium plus radiation therapy in treating children who have newly diagnosed brain stem glioma Conditions: Untreated Childhood Brain Stem Glioma Intervention / Treatment: DRUG: motexafin gadolinium, RADIATION: radiation therapy, OTHER: pharmacological study Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Clinically and radiographically (MRI) proven newly diagnosed diffuse intrinsic brainstem glioma * Greater than 50% intra-axial involvement of the pons, pons and medulla, pons and midbrain, or entire brainstem * Contiguous involvement of the thalamus or upper cervical cord allowed * Performance status - ECOG 0-2 * More than 2 months * Absolute neutrophil count at least 1,000/mm^3 * Platelet count at least 100,000/mm^3 * Hemoglobin at least 10.0 g/dL (transfusion allowed) * No glucose 6 phosphate dehydrogenase deficiency * Bilirubin no greater than 1.5 times normal * SGOT or SGPT less than 1.5 times normal * Creatinine no greater than 1.5 times normal * Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No concurrent immunomodulating agents * No other concurrent chemotherapy * Concurrent corticosteroid therapy allowed for increased intracranial pressure only * No prior cranial radiotherapy * No prior motexafin gadolinium * No other concurrent experimental agents

Study Objectives RATIONALE: rucaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and best dose of rucaparib and to see how well it works in treating patients with locally advanced or metastatic breast cancer or advanced ovarian cancer. Conditions: brca1 Mutation Carrier, brca2 Mutation Carrier, Breast Cancer, Ovarian Cancer Intervention / Treatment: DRUG: rucaparib (CO-338; formally AG-014699 or PF-01367338), GENETIC: protein expression analysis, GENETIC: western blotting, OTHER: immunohistochemistry staining method, OTHER: liquid chromatography, OTHER: mass spectrometry, OTHER: pharmacological study Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Masking: NONE

INCLUSION CRITERIA * All stages of the study (IV and oral): Patients must be proven known carriers of a mutation of BRCA1 or BRCA2 or considered to be highly likely to be carriers of a BRCA1 or 2 mutation* (score of >= 20 as per Manchester criteria) and have histologically documented locally advanced or metastatic breast cancer or advanced ovarian cancer. *Patients considered highly likely to be carriers will be tested after consenting and a BRCA1 or 2 mutation must be confirmed for the patient to be eligible to receive treatment. Oral stage 1 only: In addition to the above, patients with high grade serous ovarian cancer with unknown BRCA status may be entered into oral stage 1. * Patients with ovarian cancer (including epithelial, fallopian tube cancer and primary peritoneal cancer) who have had no more than 5 prior chemotherapy regimens in the last 5 years. For the BRCA carriers > 2 months must have elapsed since their last treatment with a carboplatin- or cisplatin-containing regimen or for high grade serous ovarian cancer patients >= 6 months. * Patients with breast cancer who have had no more than 5 prior chemotherapy regimens in the last 5 years. * Measurable disease as measured by X-ray, computerised tomography (CT), or MRI scan as defined by RECIST criteria. These measurements must be done within 4 weeks of the patient going on study. Clinical measurements must be done within one week of the patient going on study. Patients with bone disease must have other measurable disease for evaluation. Previously irradiated lesions cannot be used for measurable disease. * Life expectancy of at least 12 weeks * World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1) * Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study. Lab Test Value Required Haemoglobin (Hb) >=9.0 g/dl Neutrophils >=1.5 x 10^9/L Platelets (Plts) >=100 x 10^9/L Serum bilirubin <=1.5 x upper normal limit Alanine amino-transferase (ALT) and/or <= 2.5 x upper limit of normal (ULN) aspartate amino-transferase (AST) unless due to tumour in which case up to 5 x ULN is permissible Glomerular Filtration Rate (GFR) calculated either by the Wright formula >=50 ml/min or Cockcroft-Gault formula or by isotope clearance measurement * 18 years or over * Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up EXCLUSION CRITERIA * Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy, biological agents or investigational agents during the previous 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) before treatment. * Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient. * Known brain metastases. * Female patients able to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intrauterine device and condom, diaphragm with spermicidal gel and condom, or are surgically sterilised) 4 weeks before entering the trial, during the trial and for 6 months afterwards are considered eligible. * Male patients with partners of child-bearing potential (unless they agree to use one form of highly effective contraception such as a barrier method of condom plus spermicide during the trial and for 6 months afterwards). * Major thoracic and/or abdominal surgery in the preceding 4 weeks from which the patient has not recovered. * At high medical risk because of non-malignant systemic disease including active uncontrolled infection. * Concurrent malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and concurrent breast and ovarian carcinoma. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, are eligible for the study. * Patients with active or unstable cardiac disease or history of myocardial infarction within 6 months. Patients with cardiovascular signs or symptoms should have a MUGA scan or echocardiogram, and those patients with left ventricular ejection fraction (LVEF) below the institutional limit of normal should be excluded. * Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial. * Patients who have already received a PARP inhibitor.

Study Objectives Comparing injectable collagenase and percutaneous needle fasciotomy for Dupuytren's contracture affecting proximal interphalangeal joints. An open label, medico-independent randomized controlled trial. Conditions: Dupuytrens Contracture Intervention / Treatment: DRUG: Xiapex, PROCEDURE: Percutaneous needle fasciotomy Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * DC affecting PIP joint with Passive Extension Deficit (PED) more than 20 degrees * Clearly defined strings Exclusion Criteria: * Allergies to used medication * International Normalised Ratio more than 2.0 * Pregnancy and breastfeeding * Previous treatment for DC in affected finger * Former inclusion in the study with another string * Activity in disease at time of study * PED more than 20 degrees for Metacarpophalangeal or Distal Interphalangeal joint in affected digit

Study Objectives In this study patient's will receive the medicine Xofigo which is a radioactive drug that is FDA approved to treat prostate cancer that has spread to the bones. Xofigo has not previously been tested to treat lung cancer that has spread to the bones. Your doctors are studying the effects, good and bad, of Xofigo when used to treat lung cancer that has spread to the bones. Conditions: Non Small Cell Lung Cancer With Bone Metastatses Intervention / Treatment: BIOLOGICAL: Xofigo 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: * Age >= 18 years. * Advanced non-small cell lung cancer with bone metastases. * Stable or responding disease after completion of initial systemic chemotherapy as defined by RECIST criteria. Site to submit confirmation to BrUOG. * At least 3 weeks must have elapsed since completion of last chemotherapy and 4 weeks since last radiation, prior to first dose of Xofigo. Patients are not permitted to receive any form of 'maintenance' chemotherapy or biologic/targeted anticancer therapy while being treated on this study * Life expectancy of at least 12 weeks (3 months). * Patients with treated brain metastases are allowed, but must have brain imaging showing evidence of stability since most recent treatment for brain mets, prior to first dose of Xofigo. For patients with brain metastases only, brain imaging is required. Patients who do not have brain metastases or symptoms of potential brain metastases are not required to have baseline brain imaging, but this must be confirmed in writing * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1. * Required entry laboratory parameters within 14 days of study entry: White Blood Cell Count (WBC) >= 3,000/mm3; Absolute Neutrophil Count (ANC) >= 1,500/mm3; Platelet (PLT) count >= 100,000/mm3; Hemoglobin (Hgb) > 9g/dl, Total bilirubin level <= 1.5 x institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN ; Creatinine <= 1.5 x ULN; Albumin > 2.5 g/dL. * Concurrent treatment with bisphosphonates and denosumab is allowed. Information on start and stop date and drug with dose to be sent to BrUOG if patient to be treated concurrently. * Prior skeletal related events (pathologic fracture, radiation or surgery to bone, or spinal cord compression) are allowed if they have been managed and now patient is stable for 4 weeks prior to study entry. Must submit how events managed to BrUOG for documentation to confirm eligibility criterion. (For example, if a patient experienced a SSE and had radiation for 2 weeks they must then be stable for 4 weeks after the completion of radiation prior to study entry) * Subjects must be able to understand and be willing to sign the written informed consent form. * All acute toxic effects related to prior treatment(s) must have resolved to NCI-CTCAE v4 Grade 1 or less at the time of signing the Informed Consent Form (ICF) except for alopecia. * Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. * Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the treating physician. * Willing and able to comply with the protocol, including follow-up visits and examinations Exclusion Criteria: * Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases * No prior invasive malignancy within the prior two years. However, patients with an early stage malignancy that is not expected to require treatment in the next 2 years (such as early stage, resected breast cancer or asymptomatic prostate cancer) are eligible * Untreated brain metastases. * Any other serious illness or medical condition that in the investigator's opinion would interfere with protocol treatment, such as but not limited to: Any active infection >= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 Grade 2: Cardiac failure New York Heart Association (NYHA) III or IV * Women who are pregnant or breast-feeding. * Inability to comply with the protocol and/or not willing or who will not be available for follow-up assessments. * Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation. * Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than Ra 223 dichloride. * Major surgery within 28 days of starting study drug. Central venous catheter placement is not considered major surgery.

Study Objectives This is an open-label, non-randomized, combination study of cetuximab, gemcitabine, 5-FU, and external beam radiotherapy in patients with locally advanced, non-metastatic pancreatic cancer. Conditions: Pancreatic Cancer Intervention / Treatment: DRUG: Gemcitabine/Fluorouracil with External Beam Radiation Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological confirmation of pancreatic adenocarcinoma is required. * Only patients with unresectable, non-metastatic tumors are eligible. * Documentation of disease extent by endoscopic ultrasound and either laparotomy or laparoscopy must be performed within 42 days of registration. * All patients will also be assessed by chest x-ray and abdominal-pelvic CT scan. * Confirmation of palliative surgical bypass at the time of laparotomy or whether a biliary stent was placed will be requested. * Disease must be locoregional and not amenable to surgery based on one or more of the following criteria: * size of pancreatic tumor > 5 cm. * lymph nodes (bulky, > 2 cm, but within a radiation port) * vascular involvement or impingement of major vessels (superior mesenteric artery, superior mesenteric vein, portal vein, hepatic artery). * invasion into the adjacent structures. * Patients with either measurable or evaluable disease are eligible. * Patients with evidence of peritoneal seeding by malignancy are not eligible for the study. * Patients with other evidence of metastatic disease are not eligible. * Patients with concurrent malignancy of any site, except limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are ineligible. * Patients with any other malignancy within 5 years of study entry, except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are ineligible. * Patients may not have had prior therapy for carcinoma of the pancreas, nor prior abdominal radiation therapy. * Age > 18 years. * CTC performance status < 2. * No myocardial infarction in the past six months. * No major surgery in the past two weeks. * No uncontrolled serious medical or psychiatric illness. * Required Initial Laboratory Data: * Total bilirubin < 2.0 mg/dl * AST < 3x upper limits of normal. * Serum creatinine < 2.0 mg/dl * WBC > 3,000/mm3 (ANC>1500/mm3) * Platelets > 100,000 mm3 * CA 19-9 * Required Diagnostic procedures: * Chest X-ray * Abdominal pelvic CT scan * EUS * Staging laparoscopy or staging laparotomy Exclusion Criteria: Enrollment in this trial will be limited to patients for whom protocol therapy is safe and appropriate. Physicians should consider the risks and benefits of therapy together with all relevant medical and other considerations in deciding whether this protocol is appropriate for a particular patient. Specific considerations include: * Psychiatric illness which would prevent the patient from giving informed consent. * Serious medical illness such as uncontrolled infection, severe cardiovascular disease including recent (< 6 months) myocardial infarction or uncontrolled congestive heart failure, or other serious illness which would limit anticipated survival to < 12 weeks. * Protocol treatment would pose significant risk to an unborn child. Pregnant women should not be enrolled, and women of child-bearing age should be strongly encouraged to practice effective birth control during and for three months after the trial. * Inability to swallow medication. Patients should have adequate, unassisted oral intake.

Study Objectives The purpose of the study is to determine if ABT-751 will decrease tumors, and determine how long the tumor shrinkage can be maintained in patients with breast cancer after having had taxol or taxotere. Patients will receive ABT-751 by mouth daily for 21 days. Patients will be off drug for 7 days before starting the next cycle of drug. Conditions: Breast Cancer Intervention / Treatment: DRUG: ABT-751 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 * Stage IIIB or IV breast cancer. * Recurrent tumor after or while on taxane therapy (taxol or taxotere). * Able to tolerate normal activities of daily living. * Adequate bone marrow, kidney and liver function. Exclusion Criteria * Pregnant or breast feeding. * No anti-tumor therapy (including hormonal therapy or Herceptin) within 4 weeks of the start of ABT-751 administration.

Study Objectives In the proposed study the investigators aim to evaluate the effect of the standard of care dose (40mg) of MMC mixed with TC-3 gel (with sustained release mechanism on the drug) on low risk recurrent NMIBC lesions and to compare our findings to instillation with the standard mode of instillation- 40mg MMC in water in order to examine our hypothesis that MMC mixed with TC-3 gel will have at least non-inferior and even superior results over the standard instillation mode The investigators believe that this study is of importance of several aspects: 1. It evaluates a new mode of bladder instillation that may bypass the drawbacks of the current instillation mode. 2. If proved effective this mode of treatment might save the need of TURBT performance and serve as a new mode of tumor ablation. 3. Even if proved partially effective this mode of treatment will diminish tumors size or number thus enable a more limited TURBT procedure. 4. This mode of treatment will enable immediate medical attendance to the patient's tumor recurrence without the waiting period (resulting from queues in the medical centers) for TURBT, which might improve the patient's prognostic outcome. 5. If this experimental treatment will prove to have a better ablative effect, this could be translated to a better prophylactic effect of tumor recurrence. Conditions: Carcinoma of Urinary Bladder, Superficial Intervention / Treatment: DEVICE: 40 mg MMC gel, OTHER: Standard of care MMC mixed with water, DEVICE: 80 mg MMC gel Location: Israel, Italy, Switzerland, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient is 21 years of age or older. * Patient has signed Informed Consent Form and is willing and able to abide by the protocol. * Naïve or recurrent low grade (LG) NMIBC tumor * Recurrent patients - Single or multiple tumors * Naive patients - 2 tumors or above * No prior history of HG and/or T1 in the past 5 years. * No prior history of Tis * At least one Tumor >= 1 mm as evaluated visually by the investigator. * Largest tumor diameter <= 30 mm as evaluated visually by the investigator * Cystoscopic appearance of papillary Low grade tumor * No active urinary tract infection as confirmed by urine culture * If the patient is a female of childbearing potential , she is using two acceptable & effective methods of contraception , until 6 months post treatment * If the patient is a male he should use a condom during intercourse, for at least 48 hours post each instillation * If the patient is a male that has a partner that is a female of childbearing potential, he should be advised to use two acceptable & effective methods of contraception until 6 months post treatment. Exclusion Criteria: * Carcinoma In Situ (CIS). * "High Grade" urine cytology which is conclusive for HG. * "High Grade" tumor results in cold cup biopsy. * Tumor located in prostatic urethra. * Previous systemic chemotherapy in the last 2 years or pelvic radiotherapy. * Pregnant or breastfeeding patient. * Previous treatment with BCG within the last 12 months. * The patient did not have at least 3 months cystoscopically confirmed tumor-free interval between the last TURBT to current tumor recurrence. * Treatment with full course of intravesical chemotherapy within the 3 last months. * The patient has/had any bladder tumor with histology other than TCC. * Known contraindication or hypersensitivity to MMC or gel. * The patient has a known history of upper urinary tract urothelial carcinoma, or Renal Cell carcinoma or other renal cancer. * The patient has a known urinary retention which, according to the investigator's opinion, might lead to avoid patient receiving the treatment. * The patient has a bleeding disorder or a screening platelet count <50X109/L. * The patient has screening hemoglobin <10 mg/dL. * The patient has a condition or a concurrent severe and/or uncontrolled medical or psychiatric disease (e.g. uncontrolled diabetes, compensated congestive heart failure (NYHA III and over), myocardial infarction within 6 months of study, unstable or uncontrolled hypertension or an active uncontrolled infection), which could compromise participation, compliance with scheduled visits and/or completion. * The patient participated in an investigational interventional study within the past 90 days. * The patient has documented sever vesico-ureteral reflux or an indwelling ureteral stent. * The patient has the tumor in the bladder diverticulum. * The patient participated in a prior TheraCoat's trial with MMC and TC-3

Study Objectives Cabozantinib works by blocking the growth of new blood vessels that feed a tumor. In addition to blocking the formation of new blood cells in tumors, cabozantinib also blocks pathways that may be responsible for allowing cancers cells to become resistant to other "anti-angiogenic" drugs. Cabozantinib has been studied or is being study in research studies as a possible treatment for various types of cancer, including prostate cancer, brain cancer, thyroid cancer, lung cancer, and kidney cancer. In this research study, the investigators wish to learn if cabozantinib is effective in treating patients with pancreatic neuroendocrine and carcinoid tumors. Conditions: Carcinoid Tumor, Pancreatic Neuroendocrine Tumor Intervention / Treatment: DRUG: Cabozantinib 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: * Locally unresectable or metastatic, histologically-confirmed, carcinoid or pancreatic neuroendocrine tumor. Tumors must be considered well- or moderately-differentiated. Patients with poorly differentiated neuroendocrine carcinoma or cell carcinoma are excluded from the study. * A tumor sample is required for enrollment (except for patients diagnosed > 7 years ago). * Must have measurable disease by RECIST criteria * Must have evidence of progressive disease within 12 months of study entry * Prior or concurrent therapy with somatostatin analogs is permitted. If on somatostatin/octreotide, must be on a stable dose for at least two months. * Age >= 18 years * No major surgery or radiation in the prior 4 weeks prior to enrollment * No prior therapy with cabozantinib * ECOG Performance status <= 1 * Participants must have adequate organ and marrow function as defined below: * Absolute neutrophil count > 1,500/mcL * Platelets > 100,000/mcL * Total bilirubin <= 1.5X normal institutional limits * AST (SGOT) and ALT (SGPT) <=2.5x normal institutional limits, or < 5x if liver metastases are present * Creatinine <= 1.5x normal institutional limits or creatinine clearance > 50mL/min * Urine Protein:Creatinine ratio of <1 * Lipase < 1.5X upper limit of normal * Serum Albumin >= 2.8 g/dl * Sexually active subjects must agree to use medically accepted methods of birth control during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of child bearing potential and men who have been sterilized). * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria * Subjects receiving any other standard or investigational anticancer agents, with the exception of somatostatin/octreotide therapy. If patients has received prior cytotoxic chemotherapy, must be at least three weeks since last treatment before first dose of study treatment. * Major surgery or radiation treatment <4 weeks prior to enrollment. In addition, cannot have received radiation to the thorax or gastrointestinal tract within three months of the first dose of study treatment. * Cannot have received radionuclide treatment within 6 weeks of first dose of study treatment. * High grade or poorly differentiated neuroendocrine tumors * Ongoing immunosuppression with systemic steroids or other immune modulator * Presence of CNS metastatic disease * Uncontrolled hypertension defined by SBP > 140 or DBP > 90 despite titration of anti hypertensive medications * No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements. Congestive heart failure or symptomatic coronary artery disease within 3 months prior to enrollment * Cerebrovascular accident within prior 6 months * The subject has a history of clinically significant hematemesis or a recent history of hemoptysis of > 2.5 mL of red blood or other signs indicative of pulmonary hemorrhage or evidence of endobronchial lesion(s). * The subject has a pulmonary lesion abutting or encasing a major blood vessel. * Previous history of pulmonary embolism or deep venous thrombosis * The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (eg, clopidogrel). Low dose aspirin (<= 81 mg/day), low-dose warfarin (<= 1 mg/day), and prophylactic Low Molecular Weight Heparin (LMWH) are permitted. * At the time of screening, active peptic ulcer disease or active inflammatory bowel disease (including ulcerative colitis or Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis, or appendicitis. * History of abdominal fistula, gastrointestinal perforation, bowel obstruction, gastric outlet obstruction, or intra-abdominal abscess within six months of study enrollment. * History of GI surgery within the past 28 days. If >28 days since GI surgery, must have confirmation of complete healing before initiating treatment with study drug. * Other disorders associated with a high risk of fistula formation, including PEG tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea or esophagus. * Other clinically significant disorders such as: * Active infection requiring systemic treatment * Serious non-healing wound/ulcer/bone fracture * History of organ transplant * Concurrent uncompensated hypothyroidism or thyroid dysfunction * History of major surgery within 4 weeks or minor surgical procedures within one week before randomization * The subject has a corrected QT interval calculated by the Fridericia formula > 500ms within 28 days before randomization. * Severely impaired lung function * Concurrent malignancy (other than non-melanoma skin cancer) diagnosed within the past 3 years or any currently active malignancy * Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with the treatment protocol, breastfeeding should be discontinued if the mother is treated on protocol.

Study Objectives A non-interventional, prospective, open, multicenter study in Germany in patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies and with decision for treatment with trifluridin/tipiracil. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: Trifluridin/Tipiracil Location: Germany Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Aged >= 18 years. * Patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents. * Indication for treatment as assessed by the treating physician. * Decision for treatment with trifluridin/tipiracil. * Signed written informed consent. * Criteria according to current Summary of Product Characteristics (SmPC) for patients treated with trifluridin/tipiracil. * Ability to read and understand German. Exclusion Criteria: * Contraindications according to SmPC for metastatic colorectal cancer patients treated with trifluridin/tipiracil. * Participation in a clinical trial within 30 days prior to enrollment or simultaneous participation in a clinical trial.

Study Objectives Part A: To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of Xentuzumab (BI 836845) in combination with afatinib in patients with non-small cell lung cancer with progression following prior treatment (EGFR TKI or platinum-based chemotherapy). Part B: To evaluate the early anti-tumour activity of Xentuzumab (BI 836845) in combination with afatinib in patients with EGFR mutant non-small cell lung cancer with progression following prior irreversible EGFR TKIs. Part A and B: To evaluate the safety and pharmacokinetics of BI 836845 in combination with afatinib in patients with non-small cell lung cancer Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: BI 836845, DRUG: afatinib Location: Japan, Korea, Republic of, Singapore, Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Aged >= 18 years * Pathologically confirmed of advanced and/or metastatic stage IIIb/IV non-small cell carcinoma of lung * Activating EGFR mutation (exon 19 deletion, L858R, G719X, L861X) * Presence of EGFR activating mutation and absence of EGFR T790M in the tumour associated with the latest disease progression. Only applicable in Part B * Must have adequate fresh or archival tumour tissue at the late disease progression immediately prior to the study entry * Part A: Progression of disease (RECIST 1.1) while on continuous treatment with single EGFR TKI or for histology other than adenocarcinoma and without prior EGFR TKI treatment: progression of disease (RECIST v1.1) on platinum-based chemotherapy. Part B: Progression of disease (RECIST v1.1) while on continuous treatment with single agent of the second generation irreversible EGFR TKI (e.g. afatinib or dacomitinib) * No intervening systemic therapy between cessation of EGFR TKI and study treatment * Patient must have measurable disease per RECIST 1.1 presented after tumour biopsy for the late disease progression * Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 * Life expectancy of >= 3 months * Fasting plasma glucose < 8.9 mmol/L (< 160mg/dL) and HbA1C < 8% * Adequate organ function * Recovered from any previous therapy related toxicity to <= Grade 1 at study entry (except for stable sensory neuropathy <= Grade 2 and alopecia) * Written informed consent that is consistent with ICH-GCP guidelines and local regulations * No known potentially targetable mutation other than IGF signaling pathway or EGFR or no available treatment for potentially targetable mutation Exclusion criteria: * Part A only: For patient who has been treated with afatinib: last treatment at reduced dose below the assigned dose level * Patient whose disease progressed on insufficient dose of EGFR TKI immediately prior to study in the opinion of the investigator * More than 2 prior EGFR TKI treatment regimens for Part B * Chemotherapy, biological therapy or investigational agents (except EGFR TKIs) within 4 weeks * Use of previous EGFR TKIs except afatinib within 3 days * Radiotherapy within 4 weeks prior to the start of study treatment * Active brain or subdural metastases * Meningeal carcinomatosis. * Major surgery (as judged by the investigator) within 4 weeks * Known hypersensitivity to afatinib, monoclonal antibody * Prior severe infusion-related reaction to a monoclonal antibody * History or presence of clinically relevant cardiovascular abnormalities * Female patients of childbearing potential (see Section 4.2.2.3) and male who are able to father a child * Any history of or concomitant condition that, in the opinion of the investigator not to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug * Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. * Disease that is considered by the investigator to be rapidly progressing or life threatening such as extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumour (subjects who are intended for urgent chemotherapy) * Requiring treatment with any of the prohibited concomitant medications * Known pre-existing interstitial lung disease (ILD) * Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug * Active hepatitis B infection active hepatitis C infection and/or known HIV carrier. * Previous treatment with agents targeting the insulin like growth factor (IGF) signalling pathway. * Previous treatment with EGFR TKI which cannot be documented as either reversible or irreversible (Part B only) * Part B only: Prior treatment with third generation irreversible EGFR TKI (e.g. AZD9291 or CO-1686)

Study Objectives Investigators will determine whether a treatment paradigm of up-front neck dissection, to more accurately pathologically stage patients, minimizing the number of treatment modalities in patients with low risk oropharyngeal squamous cell carcinoma, can improve quality of life. Conditions: Oropharyngeal Squamous Cell Cancer Intervention / Treatment: PROCEDURE: Neck Dissection, PROCEDURE: Standard-of-Care (SOC) Transoral Surgery of Primary Site, RADIATION: SOC Radiation, DRUG: SOC Carboplatin, DRUG: SOC Paclitaxel, PROCEDURE: Videofluoroscopy 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 pathologically-confirmed, previously untreated, p16-positive oropharyngeal squamous cell carcinoma * Patients must have pretreatment neck and chest imaging * Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon * Patients with T stage T1-3 * Patients with N stage N0-N2c * ECOG (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) Performance status 0-2 * Patients are adults (Age >18) * Patients must agree to biospecimen submission for tissue and serum processing and storage for secondary biomarker studies * Patients must give documented informed consent to participate in this study. * Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of chemoradiation (treatment) and for 3 months after discontinuing treatment. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to starting treatment. * Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after study treatment. Women not of childbearing potential will be defined as all women older than age 50 and anovulatory for 12 months. * Sexually active males must use a condom during intercourse while receiving chemoradiation and for 90 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Likewise, male subjects should not donate sperm during the time they are receiving chemoradiation and for 90 days after stopping treatment. Exclusion Criteria: * Prior head and neck radiation or prior chemotherapy for HNSCC (Head and Neck Squamous Cell Carcinoma) * Patients with T4 disease * Patients with N3 disease * FNA evidence of squamous cell carcinoma involving 3 or more lymph nodes * Patients with matted lymph nodes, defined as three nodes abutting one another with loss of intervening fat plane that is a replaced with radiologic evidence of extracapsular spread * Patients with an outside primary site biopsy showing perineural or perivascular invasion * Documented evidence of distant metastases. * Active infection * Patients residing in prison. * Age < 18 years * Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification * Unstable angina or a history of myocardial ischemia within prior 6 months * Patients with any of the following laboratory values at baseline: * Absolute neutrophil count (ANC) < 1,000/mm3 * Platelets < 75,000/mm3 * Hemoglobin < 9.0 gm/dL * Calculated or measured creatinine clearance (method determined by the prescribing physicians) < 50 ml/min * Bilirubin > 1.5 x ULN (Upper Limit of Normal), except for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN * Aspartate transaminase (AST) > 3.0 x ULN * Alanine transaminase (ALT) > 3.0 x ULN * Pregnancy or breastfeeding female. * Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Study Objectives A randomized, open label phase 3 study of irinotecan liposome injection (ONIVYDE®) versus topotecan in patients with small cell lung cancer who have progressed on or after platinum-based first-line therapy The study was conducted in two parts: 1. Dose determination of irinotecan liposome injection 2. A randomized, efficacy study of irinotecan liposome injection versus topotecan Conditions: Small Cell Lung Cancer Intervention / Treatment: DRUG: Irinotecan liposome injection, DRUG: Topotecan Location: Hungary, Germany, Korea, Republic of, Turkey, Italy, Brazil, Romania, Spain, Serbia, United States, Belgium, Australia, Ukraine, Taiwan, China, Russian Federation, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * At least 18 years of age. * Able to understand and provide an informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy >12 weeks * Histopathologically or cytologically confirmed small cell lung cancer * Evaluable disease as defined by RECIST Version 1.1 guidelines (patients with non measurable lesions only are eligible). * Radiologically confirmed progression on or after first-line platinum based chemotherapy (carboplatin or cisplatin), or chemo-radiation including platinum-based chemotherapy for treatment of limited or extensive stage Small Cell Lung Cancer (SCLC). In addition to platinum-based regimen, one line of immunotherapy as monotherapy or in combination, in first or in second line setting is allowed. * Recovered from the effects of any prior chemotherapy, surgery, radiotherapy or other anti-neoplastic therapy (recovered to Grade 1 or better, with the exception of alopecia, peripheral neuropathy, or ototoxicity). * Adequate bone marrow reserves * Adequate hepatic function * Adequate renal function * Electrocardiogram during the Screening period without any clinically significant findings, per investigator's assessment * Patients with certain types of asymptomatic CNS metastases that meet ALL the following criteria are eligible. 1. Patients with asymptomatic CNS metastases prior to enrollment 2. Prior radiation for CNS metastatic disease is completed >=4 weeks prior to enrollment 3. CNS metastases that are stable or have decreased according to the post radiation follow-up scan that is conducted at least 4 weeks after completion of radiation treatment for CNS lesion. 4. Patients have discontinued corticosteroids or are on stable low-dose steroids (prednisone or equivalent 10 mg daily or less) for at least 1 week after completion of radiation for CNS lesion prior to enrollment. Exclusion Criteria * Any medical or social condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results * Pregnant or breast feeding; * Patients with large cell neuroendocrine lung carcinoma. * Patients who have received prior topoisomerase I inhibitor treatment, retreatment with platinum-based regimen, antibody-drug conjugates or molecular targeted agents, more than one line of immunotherapy, or any other additional regimen of prior cytotoxic chemotherapy. * Patients with the symptomatic Central Nervous System (CNS) metastasis and/or who have developed new or progressive brain metastasis within 3 months following prophylactic and/or therapeutic cranial radiation (whole brain stereotactic radiation). * Patients with carcinomatous meningitis. * Unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week or strong CYP3A4 inducers at least 2 weeks prior to receiving the first dose of irinotecan liposome injection. * Have a previous or concurrent cancer that is distinct in primary (non-pulmonary) site or SCLC histology * Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is less, prior to the first scheduled day of dosing in this study. * Severe cardiovascular and pulmonary diseases * New York Heart Association Class III or IV congestive heart failure, ventricular arrhythmias, or uncontrolled blood pressure. * Active infection * Known hypersensitivity to any of the components of irinotecan liposome injection, other liposomal products, or topotecan. * Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1.

Study Objectives This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of etrumadenant (AB928) in combination with mFOLFOX in participants with advanced metastatic gastroesophageal Cancer (GEC) or colorectal cancer (CRC). Conditions: GastroEsophageal Cancer, Colorectal Cancer Intervention / Treatment: DRUG: etrumadenant, DRUG: mFOLFOX Location: United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Male or female participants >= 18 years * Histologically confirmed gastroesophageal cancer or colorectal cancer that is metastatic, advanced or recurrent with progression * Participants for whom mFOLFOX is considered appropriate therapy * Must have at least 1 measurable lesion per RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. * Must have received standard of care, including potentially curative available therapies or interventions. * Confirm that an archival tissue sample is available and <= 24 months old; if not, a new biopsy of a tumor lesion must be obtained. * Adequate organ and marrow function * Previously treated central nervous system metastases, meeting the following criteria: * No evidence of progression by magnetic resonance imaging for at least 4 weeks prior to first dose. * Neurologic symptoms returned to baseline. * No immunosuppressive doses of systemic corticosteroids for at least 2 weeks before investigational product administration. * No carcinomatous meningitis. Exclusion Criteria: * Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product. * Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous (eg interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs, or concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic or absorbable topical corticosteroids. * 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 study, starting with the pre-screening or screening visit through 30 days after the last dose of etrumadenant in combination with mFOLFOX. * Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy. * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study. * Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or prostate. * Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks prior to Day 1 or has not recovered (ie, >= Grade 1 or baseline) from AEs due to a previously administered agent, except <= Grade 2 alopecia or <= Grade 2 neuropathy and other AEs <= Grade 2 considered not clinically significant by the Medical Monitor and Investigator. * Use of other investigational drugs (drugs not marketed for any indication) within 28 days of investigational product administration.

Study Objectives * Safety and tolerability of three regimens of intravesically administered BC-819/PEI and BCG (number of participants with AEs, discontinuations due to AEs) * Recurrence after treatment with BC-819/PEI and BCG * Approximately 38 patients with superficial transitional cell carcinoma TCC) of the bladder * After initial evaluation and qualification, patients will be randomized to one of three treatment groups, either alternating, sequential or twice weekly Conditions: Transitional Cell Carcinoma of Bladder Intervention / Treatment: DRUG: BC-819/PEI, DRUG: BCG Vaccine Location: Israel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with superficial papillary transitional cell carcinoma of the bladder for whom BCG is clinically indicated. If CIS is present, diagnosis needs to be confirmed by biopsy prior to the start of the study. * Males or females more than 18 years old * All papillary tumors must be resected within 8 weeks prior to the start of study therapy. * ECOG performance status 2 or less. * Adequate hematologic function, as demonstrated by 1. Hemoglobin 10 g/dL or higher 2. ANC 1.5 x 109/L or higher 3. Platelets higher than 100 x 109/L * Adequate liver and renal function as demonstrated by 1. AST and ALT each 3.0 x ULN or less 2. Total bilirubin 1.5 x ULN or less 3. Creatinine 1.5 X ULN OR less, creatinine clearance >60 mL/min * If fertile and sexually active, must use adequate contraception * Must be able to comply with protocol requirements, including attendance at required clinic visits. * Patients must provide written informed consent. - Exclusion Criteria: * Patients who are candidates for either partial or total bladder resection, unless either medically contraindicated or who have refused surgery. * Patients with a tumor in a diverticulum, in the prostatic urethra, or covering the ureteral orifice. * Patients who have received cytotoxic drugs, systemic corticosteroids or any investigational drug for any indication within 4 weeks of the start of protocol treatment. * Patients who have received any intravesical therapy other than surgical resection within 8 weeks prior to the start of protocol treatment. * Patients who have received radiation therapy for bladder cancer at any time or for any condition within 4 months prior to the start of protocol treatment. * Patients who have active infections, including urinary tract infections, whether viral, bacterial or fungal and requiring therapy. * Patients who are receiving coumadin. * Patients who have had to discontinue a past course of BCG due to toxicity. * Patients who are having urinary tract signs or symptoms from recent urinary tract procedures or manipulations, such as biopsies or catheterizations. * Patients who are known to be HIV positive. * Females who are pregnant or breast feeding. * Presence of any medical, psychological or social condition or situation which may, in the investigator's opinion, make it difficult for the patient to tolerate study medication or comply with study procedures and other requirements. This includes but is not limited to active infections, poorly controlled diabetes, uncontrolled cardiac arrhythmias, angina pectoris, or hypertension. -

Study Objectives The purpose of this trial is to determine the maximum tolerated dose and the dose-limiting toxicity of biweekly oxaliplatin in combination with fixed doses of irinotecan, 5-fluorouracil/leucovorin and gemcitabine in patients with metastatic solid tumors or adenocarcinoma of the pancreas. Conditions: Pancreatic Neoplasms Intervention / Treatment: DRUG: gemcitabine; irinotecan; leucovorin; 5-fluorouracil; oxaliplatin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of a solid tumor, OR advanced or metastatic disease that is refractory to conventional treatment or for which no standard therapy exists. * Age > 18 years old. * A performance status of >= 60 on the Karnofsky scale * Life expectancy of at least 12 weeks. * Patients must give written informed consent as per institutional and federal regulatory requirements. * No chemotherapy, immunotherapy or radiotherapy for at least four weeks prior to entry in the study (six weeks for nitrosureas or mitomycin C). Patients may not receive concurrent chemotherapy, immunotherapy or radiotherapy while participating in this study. Patients may not receive concurrent treatment with any other investigational drug while on this protocol. * Patients must have measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST). * Absolute granulocyte count of > 1,500/mm3 and a platelet count > 100,000/mm3. * Patients must have adequate liver and renal function defined by a bilirubin of <= 2.0 mg/dl, and a creatinine of <= 1.5 mg/dl respectively. * Patients must be able to stay in the general area for the duration of their treatment on this clinical research study. * Men and women who are fertile must use adequate contraception. Premenopausal women must have a negative pregnancy test documented prior to study entry. * Patients must be disease-free of prior invasive malignancies for >= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Exclusion Criteria: Individuals excluded from participating in this study are described below. * Women who are pregnant or breast-feeding * Patients with clinical signs of brain involvement or leptomeningeal disease. * Patients with progressive sensory neuropathy or progressive hearing loss or tinnitus. * Patients with other serious illness or medical conditions, including but not limited to the following: * congestive heart failure or angina pectoris * previous history of myocardial infarction within 1 year from study entry * uncontrolled hypertension or arrhythmias * active infections * unstable diabetes mellitus

Study Objectives The purpose of this study is to evaluate the efficacy and the safety of paclitaxel given weekly in patients with advanced or recurrent breast cancer Conditions: Breast Cancer Intervention / Treatment: DRUG: Paclitaxel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with primary advanced inoperable disease who were refractory to chemotherapy * Patients with recurrent disease following post-operative adjuvant chemotherapy * Patients who were not amenable to post-recurrence chemotherapy Exclusion Criteria: * Patients with serious, uncontrolled medical illness * Patients with previous therapy with taxanes

Study Objectives This is an open label, non-randomized, Phase 1b/2a, dose escalation and dose confirmation study of ZEN003694 in combination with enzalutamide in patients with mCRPC. Conditions: Metastatic Castration-Resistant Prostate Cancer Intervention / Treatment: DRUG: ZEN003694, DRUG: Enzalutamide 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: * Males age >= 18 years * Metastatic, castrate resistant, histologically confirmed prostate cancer; surgically castrated or continuous medical castration for >= 8 weeks prior to screening * Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate laboratory parameters [absolute neutrophil (ANC), platelets, asparate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening * Dose Escalation Cohort DE-A: Prior progression on enzalutamide or apalutamide at any time by PCWG2 criteria and receiving a stable dose of enzalutamide at the start of study treatment. * Dose Escalation Cohort DE-B: Enzalutamide-naïve and apalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and receiving a stable dose of enzalutamide at the start of study treatment. * Dose Confirmation Cohort A (DC-A) only: Currently receiving enzalutamide as most recent systemic therapy for mCRPC and have experienced PSA progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. Patients may or may not have experienced prior progression on abiraterone. * Dose Confirmation Cohort B (DC-B) only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone. Exclusion Criteria: * Any history of brain metastases or prior seizure or conditions predisposing to seizure activity * Have previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-001) * Have received prior systemic anti-cancer therapy (including abiraterone) or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug * Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry * Radiation therapy within 2 weeks of the first administration of study drug * Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry) * Have received prior investigational anti-androgen therapy, including ARN-509 * Currently receiving medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. Strong inducers, inhibitors and substrates must be discontinued at least 7 days prior to the first administration of study drug. * Not a candidate for enzalutamide treatment, in the opinion of the Investigator

Study Objectives This is a phase I study aimed at identifying safe doses of DMXAA in patients with solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: DMXAA Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed solid tumor that is not amenable to any standard therapy or is refractory to conventional therapy * Performance status WHO 0-2 * Life expectancy greater than 3 months * Hemoglobin at least 90 g/L; WBC at least 3,000/mm3; Platelet count at least 100,000/mm3 * Bilirubin within normal limits; ALT less than 2 times upper limit of normal (ULN); Alkaline phosphatase less than 2 times ULN * Creatinine less than 130 umol/L * INR and APTT within normal limits * Fertile patients must use effective contraception * At least 4 weeks since prior anticancer therapy and recovered from toxic effects Exclusion Criteria: * Concurrent malignancy except cone biopsied carcinoma in situ of the cervix and adequately treated basal or squamous cell carcinoma of the skin * Other serious medical condition * Uncontrolled infection or serious infection within the past 28 days * Pregnant or lactating * Treatment with glucocorticosteroids within previous two weeks

Study Objectives Drg-drug Interaction (DDI) study to assess the effect of INC280 on the pharmacokinetics of midazolam and caffeine in patients with cMET-dysregulated advanced solid tumors Conditions: cMET-dysregulated Advanced Solid Tumors Intervention / Treatment: DRUG: INC280, DRUG: Midazolam, DRUG: Caffeine Location: Bulgaria, Italy, Spain, United Kingdom, Denmark, United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Patients must have: * advanced solid tumors and have confirmed cMET dysregulation * at least one measurable lesion as defined by RECIST 1.1. * recovered from all toxicities related to prior anti-cancer therapies * adequate organ function * ECOG performance status (PS) of 0 or 1 Exclusion Criteria: Patients must not have: * known hypersensitivity to any of the excipients of INC280 or to benzodiazepines or known intolerance and hypersensitivity to caffeine * symptomatic central nervous system (CNS) metastases who are neurologically unstable * presence or history of carcinomatous meningitis * history of another primary malignancy that is currently clinically significant or currently requires active intervention * Clinically significant, uncontrolled heart diseases, including QTcF >= 450 ms (male patients), >= 460 ms (female patients) on the screening ECG * Thoracic radiotherapy to lung fields <= 4 weeks prior to starting INC280 * Major surgery within 4 weeks prior to starting INC280 * Patients receiving unstable or increasing doses of corticosteroids. * Impairment of GI function or GI disease that may significantly alter the absorption of INC280 * Patients who have received or consumed, or are expected to receive or consume midazolam or caffeine-containing products (e.g., tea, coffee, cola), within 2 days prior to Day 1 and during the whole duration of the DDI phase (i.e., from Day -2 to Day 12) Other protocol-defined inclusion/exclusion criteria may apply

Study Objectives The goal of this clinical research study is to test the safety of defined green tea catechin extract at different dose levels. Researchers also want to find out what effects, good and bad, it may have on individual and their risk for esophagus cancer. Esophagus cancer is an increased risk associated with Barrett's esophagus. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of defined green tea catechin extract may prevent esophageal cancer. Conditions: Barrett Esophagus Intervention / Treatment: OTHER: placebo, DRUG: defined green tea catechin extract Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Histologically-confirmed diagnosis of Barrett's metaplasia within 12 months prior to trial entry * Note: The presence of LGD may be subject to disagreement between pathologists; this will not affect trial entry, since patients with or without LGD are eligible to participate; all cases in which there is disagreement regarding the presence of LGD will be reviewed by a third pathologist for histological classification prior to the efficacy analysis * Cases of short-segment (less than or equal to 3 cm) Barrett's esophagus must be large enough to allow adequate sampling of tissue without completely resecting the metaplasia * ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%) * Leukocytes greater than or equal to 3,000/UL * Absolute neutrophil count greater than or equal to 1,500/UL * Platelets greater than or equal to 100,000/UL * Total bilirubin within normal institutional limits * AST (SGOT)/ALT (SGPT) less than or equal to institutional ULN * Creatinine within normal institutional limits * Alkaline phosphatase less than or equal to the institutional ULN * Willingness to abstain from all tea consumption while on the study drug * Willingness to record intake of caffeine-containing foods and medications while on the study * A significant portion of caffeine intake occurs from "hidden" sources, including medications and foods * Study subjects will be provided a list of permissible medications, beverages and foods which contain caffeine * Participants may continue therapy with proton pump inhibitors, nonsteroidal anti-inflammatory agents, and celecoxib or rofecoxib * Pregnancy testing to within 2 weeks prior to randomization * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation * If a female participant does become pregnant while on study, she will be removed from the study * Willingness to comply with all treatment and follow-up procedures * Willingness to wait at least one month since last endoscopic evaluation * Ability to understand and willingness to sign a written informed consent document * Inclusion of women and minorities: both men and women and members of all races and ethnic groups are eligible for this trial Exclusion Criteria: * Histologically confirmed high-grade dysplasia * Histologically confirmed diagnosis of invasive carcinoma of the esophagus * Prior endoscopic therapy for Barrett's esophagus, including mucosal ablation, resection and esophagectomy, and photodynamic therapy * History of esophageal strictures with moderate-to-severe dysphagia or odynophagia that may interfere with ingestion/swallowing of the study drug * Trial participation will be determined by the study investigator after consideration of other factors including severity of dysphagia and odynophagia, necessity for treatment of strictures, and nutritional status * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Poly E * Participants may not be receiving any other investigational agents within 30 days prior to randomization or during the study * Use of medications, herbs, and vitamin and mineral supplements that contain tea compounds should not be taken while participating in the study and on study drug and for 30 days prior to trial entry * If patients are consuming any of these items and would like to participate in this study, then a 30-day voluntary washout will be required * Uncontrolled or significant co-morbid illness including, but not limited to, active or serious infection requiring intravenous antibiotics; symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia; * Stages Ia or Ib invasive squamous cell carcinoma of the cervix treated by surgery and/or radiation therapy, stage Ia grade 1 adenocarcinoma of the endometrium treated with surgery; patients receiving active chemotherapy or radiation; or psychiatric illness/social situations that would limit compliance with study requirements * Participants will not take aspirin, aspirin-containing substances, Coumadin (warfarin), heparin, or iron for 5 days before each endoscopy * Active gastrointestinal bleeding; predisposing condition to gastrointestinal bleeding (including but not limited to gastritis, diverticulitis, colitis, and hemorrhoids); active malignancy diagnosed or treated within 5 years, except for squamous cell carcinoma of the skin, basal cell carcinoma of the skin, carcinoma in situ

Study Objectives Eligible patients will be randomized in a ratio of 2:1 to receive either chemotherapy (a taxane and a platinum compound) plus CPG 7909 Injection or chemotherapy alone. Protocol therapy will be administered until disease progression or intolerable toxicity. CpG 7909 Injection will be administered subcutaneously, on Weeks 2 and 3 of each three-week cycle (days 8 and 15) and chemotherapy will be administered on Week 1 (Day 1). Patients will undergo complete disease evaluation at the end of every other treatment cycle until disease progression. Conditions: Carcinoma, Non-Small Cell Lung Intervention / Treatment: DRUG: CPG 7909, DRUG: Chemotherapy, DRUG: Chemotherapy Location: United States, Germany, Canada 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 non-small cell lung cancer that is beyond surgical cure or that is metastatic (Stage IIIB or IV according to AJCC). * Patients must have measurable disease according to the RECIST criteria. Exclusion Criteria: * Prior treatment with chemotherapy; patients may have received prior radiotherapy. * Patients with suspected or known CNS metastases.

Study Objectives This randomized phase III trial is studying low-dose prednisone or methylprednisolone to see how well they work compared with standard-dose prednisone or methylprednisolone in treating patients with newly diagnosed acute graft-versus-host disease (GVHD). Glucocorticoids, such as prednisone or methylprednisolone at a starting dose of 2 mg/kg/day are standard treatment for acute graft-versus-host disease caused by a donor stem cell transplant. It is not yet known whether low-dose glucocorticoids are more effective than standard-dose glucocorticoids in treating acute graft-versus-host-disease Conditions: Graft Versus Host Disease, Recurrent Adult Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: prednisone, DRUG: methylprednisolone, OTHER: questionnaire administration Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with newly diagnosed acute GVHD (>= grade IIa) for whom, in the judgment of the attending physician, initial treatment with systemic glucocorticoids is indicated * Patient or guardian able and willing to provide informed consent Exclusion Criteria: * Hallmarks of chronic GVHD * GVHD after donor lymphocyte infusion (DLI) * Patient unwilling to remain in Seattle under the care of the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) through day 42 after the start of treatment for GVHD * Uncontrolled infection or other underlying comorbidity (i.e. severe psychiatric illness) that precludes the use of "standard-dose" prednisone * Recent diagnosis of recurrent or progressive malignancy that precludes the use of "standard-dose" prednisone * Any prior systemic therapy for acute GVHD (Patients may receive up to 2 doses of low-dose prednisone prior to randomization; low-dose prednisone is defined as 0.5 mg/kg/dose for patients who present with grade IIa GVHD and 1 mg/kg/dose for those who present with grade IIb-IV GVHD) * Enrollment on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) trial 0802

Study Objectives This is a phase II study where chemotherapy (gemcitabine) is given into the urinary bladder. Conditions: Bladder Neoplasms Intervention / Treatment: DRUG: Gemcitabine Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Superficial bladder cancer * No prior chemotherapy Exclusion Criteria: * Grade 3 tumors * Papillary tumors invading connective tissue * Significant urologic disease, possible interfering with intravesical therapy

Study Objectives eligible subjects will receive treatment beginning on Day 1 of each 3-week dosing cycle for pembrolizumab. Treatment with pembrolizumab will continue until documented disease progression, unacceptable adverse event(s),intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, subject receives 24 months of pembrolizumab, or administrative reasons requiring cessation of treatment. Conditions: Biliary Tract Cancer Intervention / Treatment: DRUG: MK3475 Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Have histologically or cytologically-confirmed diagnosis of biliary tract cancer including intra- and extra-hepatic biliary tract cancer * Have metastatic disease or locally advanced, unresectable disease with feasible biopsy sites (baseline and follow up) * Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum/gemcitabine or any platinum/ fluoropyrimidine doublet. * Have measurable disease based on RECIST as determined by investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained endoscopic biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides. 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 squamous cell or sarcomatoid biliary duct cancer. Ampulla of Vater cancer. Gall bladder cancer * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy 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 any of its excipients.

Study Objectives In the UK, around 1 in 16 men and 1 in 20 women will develop bowel cancer at some point in their lives. Most bowel cancers happen when a type of growth in the bowel called an adenoma eventually becomes cancerous. Cutting out adenomas reduces the risk of developing bowel cancer. Certain people are more likely to have adenomas than others, for example people who are overweight. People who are overweight are also more likely to develop liver disease by laying too much fat down in the liver. Studies in Asia have shown that people with fatty liver disease are more likely to have adenomas and these are more commonly found in the part of the bowel (right colon) furthest from the bottom end. Information on the link between obesity, fatty liver disease and adenomas is very limited, particularly in the Western population. The investigators will assess the link between body weight, fatty liver and adenomas in the UK population. 1430 patients will be invited; some through the bowel cancer screening programme and some with symptoms such as low blood count, bleeding or changed bowel habit. These patients will already have been referred for a camera test looking into the bowel, called a colonoscopy. Information including height, weight and some health questions will be taken. Blood samples will be taken. The investigators will compare the number of patients with adenomas who have liver disease or who are overweight with those who don't. This information will be used to develop a scoring system to predict risk of adenomas. This will help the investigators to decide if undertaking colonoscopies in these patients will identify those at increased risk of bowel cancer. Conditions: Colorectal Adenoma, Colorectal Neoplasm, Colorectal Cancer, Obesity, Metabolic Syndrome, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis Intervention / Treatment: DIAGNOSTIC_TEST: Colonoscopy Location: United Kingdom Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Aged 18 years and over * Able to give informed consent * Indications: 1. Patients with positive faecal occult blood test (FOBt) referred for index colonoscopy as part of Bowel Cancer Screening Programme 2. Colonoscopy conversion from Bowelscope 3. Index diagnostic colonoscopy due to new gastrointestinal symptoms (including but not restricted to diarrhoea, change in bowel habit, abdominal pain, PR bleeding, weight loss), iron deficiency anaemia, family history of CRC, abnormal findings on cross sectional imaging Exclusion Criteria: * Absolute contraindication to colonoscopy * Unable to give informed consent * Known colorectal cancer * Known polyposis syndrome * Previous total/subtotal colectomy * Known colonic stricture which would prevent completion of colonoscopy * Attending for therapeutic procedure * Attending for assessment of a known lesion * Attending for assessment of known inflammatory bowel disease (IBD) * Attending for surveillance colonoscopy (polyp surveillance, post colorectal cancer surveillance, IBD surveillance) * Colonoscopy within the last 5 years

Study Objectives This is a phase 1 study in which 2 to 72 patients with advanced cancer will receive oral doses of rigosertib, a new investigational (unapproved) anti-cancer drug. The objective of the study is to determine the highest dose of drug that can be given safely. The study will start by testing a low dose. If this dose is safe, then, higher and higher doses will be tested as long as the previous lower dose was safe. Safety will be determined by looking for any side effects or unusual laboratory values. It is important to know the highest safe dose so that additional studies can be done. The drug will be given in the form of capsules twice or three times a day for 21 consecutive days of 21-day cycles. Conditions: Solid Tumor Intervention / Treatment: DRUG: rigosertib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed solid tumor (leukemias and lymphomas excluded). * Malignancy that is incurable and for which standard (FDA approved or established standard clinical practice), curative, or palliative measures do not exist or are no longer effective. * ECOG performance status 2, 1 or 0. * Life expectancy greater than 6 months. * One or more measurable lesion(s) ("target lesion[s]"), that can be accurately measured in at least 1 dimension with longest diameter equal to or greater than 20 mm using conventional techniques (computed tomography [CT] scan or magnetic resonance imaging [MRI]) or equal to or greater than 10 mm with spiral CT scan. * If female, has a negative screening for pregnancy. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry (hormonal or barrier method of birth control; abstinence) and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand the nature of the study and any hazards of participating in it, to communicate satisfactorily with the investigator, and to participate in, and comply with, the requirements of the entire study. * Willing to adhere to the prohibitions and restrictions specified in this protocol. * Patient must have signed an informed consent document. Exclusion Criteria: * Recent major surgery (within the past 14 days). * Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C). * Among patients with prior doxorubicin chemotherapy, only those with no more than a total cumulative dose of 450 mg/m2 of the drug. * Definitive radiotherapy (over 10 fractions and maximal area of hematopoietic active bone marrow treated was greater than 25%) within 4 weeks prior to entering the study. * Palliative radiotherapy (10 or less fractions) within 2 weeks prior to entering the study. * Residual adverse events (except alopecia, stable residual neuropathy, and residual hand, foot syndrome) and ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum value less than 130 Meq/L) due to previously administered agents, which have not recovered at grade 1 severity level or below before study entry. * Receiving any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy while on study. Exceptions are long-term hormonals for prostate (e.g. goserelin) and octreotide for neuroendocrine malignancies. * Previous bone marrow transplant. * Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ON 01910.Na. * Uncontrolled intercurrent illness. * Hgb less than 9 gm/dL (must not require transfusional support but erythropoietin therapy is permitted). * WBC less than 4,000/microliter. * Absolute neutrophil count less than 1,500/microliter. * Platelets less than or equal to 100,000/microliter. * Total bilirubin greater than 1.5 times institutional upper normal limit. * AST(SGOT)/ALT(SGPT) equal to or greater than 2.5 x institutional upper normal limit. (If liver function abnormalities are due to metastatic disease, patients are eligible provided the transaminases are < 5 times institutional upper normal limit.). * Serum creatinine greater than 2 times upper limit of institutional normal value. * Pregnant and nursing women. * HIV-1 positive patients receiving combination anti-retroviral therapy.

Study Objectives This is a single arm, open-label, phase II trial of nivolumab, ipilimumab and short-course radiation therapy in adult patients with newly diagnosed, MGMT unmethylated GBM with the primary objective of determining the overall survival at 1 year. Conditions: MGMT-unmethylated Glioblastoma (GBM), GBM Intervention / Treatment: DRUG: Nivolumab, DRUG: Ipilimumab, RADIATION: Radiation Therapy (RT) 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: * Male or female subjects aged >=18 years. * Histopathological evidence of glioblastoma or gliosarcoma, WHO grade IV. * Tumor MGMT promoter DNA not methylated (i.e., unmethylated) by central testing. * Maximal tumor diameter (including residual tumor and resection cavity if subjects had tumor resection rather than only stereotactic biopsy) of 6.6 cm or less. Maximal tumor size allowed is derived from an estimated maximal radiotherapy planning target volume (PTV) of 150 cm3. * Subjects must not have received any prior standard or investigational anti-tumor therapy other than surgery and must not intend to receive any standard or investigational anti-tumor therapy other than the study regimen. * Karnofsky performance status (Appendix 2) of >=60. * Availability of a paraffin-embedded or frozen tumor-tissue block with a minimum of 1 cm2 of tumor surface area, or 20 unstained slides from the glioblastoma tissue specimen if a tumor block cannot be submitted. * Subjects must start study agent within 6 weeks from the first diagnostic surgery for glioblastoma. * An interval of at least 2 weeks for surgical resection and 1 week for stereotactic biopsy from the start of study treatment. * A contrast-enhanced MRI must be obtained within 7 days of the first dose of study treatment. * Adequate hematologic, hepatic, and renal function defined by * White blood cell count >= 2.0 x 109/L * Absolute neutrophil count >= 1.5 x 109/L * Platelet count >= 100 x 109/L * Hemoglobin > 9 g/dL * Serum creatinine <=1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min according to the Cockcroft-Gault formula or local institutional standard method * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 x ULN * Total bilirubin <= 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) * Women of child-bearing potential (WOCBP) and men able to father a child must agree to use highly effective contraception (any contraceptive method with a failure rate of less than 1% per year) while on study drug and for 23 weeks (for women) or 31 weeks (for men) after the last dose of study drug. 1. WOCBP must have a negative serum or urine pregnancy test within 24 hours of initiation of study drug. 2. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to be defined as post-menopausal. 3. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. 4. Highly effective contraceptive measures include: stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomy and sexual abstinence. 5. Contraception is not required for men with documented vasectomy. 6. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation. 7. Women must not be breastfeeding. * Willing to and capable of providing written informed consent prior to any study related procedures. * Ability and willingness to comply with all study requirements, including scheduled visits, treatment plans, laboratory tests, and other study-related procedures. Exclusion Criteria: * Prior use of any standard or investigational anti-tumor therapy other than surgery * Planned participation in another study of an investigational agent or investigational device or planned use of any other agent or therapeutic device intended for therapy of glioma. * Prior systemic 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 costimulation or immune checkpoint pathways. * Primary brainstem or spinal cord tumor. * Diffuse leptomeningeal gliomatosis. * Known mutation of the IDH1 or IDH2 genes in the tumor, since glioblastomas with these mutations have different biology and are associated with improved prognosis. * Systemic treatment with either immunosuppressive doses of corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. 1. Subjects on a standard high-dose steroid taper after craniotomy or stereotactic biopsy may have received a higher dose of corticosteroids within 14 days of registration, however must be at a dose < 10 mg daily prednisone or bioequivalent per day within 5 days prior to initiation of study drug. 2. Administration of steroids through a route known to result in a minimal systemic exposure [i.e., intranasal, intraocular, inhaled, topical, or local injection (e.g., intra-articular injection) corticosteroids (<5% of body surface area)] are permitted in the absence of active autoimmune disease. 3. Subjects requiring adrenal replacement with corticosteroids are eligible if the steroids are at doses <= 10 mg prednisone or bioequivalent per day in the absence of active autoimmune disease. 4. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed. * Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. The following conditions are not exclusions (subjects with the following conditions are permitted): a.Patients with diabetes type I, vitiligo, residual hypo- or hyperthyroidism due to autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic immunosuppressive treatment, or autoimmune conditions not expected to recur in the absence of an external trigger. * Prior organ transplantation, including allogeneic stem cell transplantation. * Known history of, or any evidence of active, non-infectious pneumonitis within the last 5 years. * Known severe (NCI-CTCAE v4.03 Grade 3 or 4) infusion-related allergy or acute hypersensitivity reaction attributed to any monoclonal antibody, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma). * Unable tolerate an MRI, or have a contraindication to MRI. * Active infection requiring systemic therapy. * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. * Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (HCV antibody) indicating acute or chronic infection. * Vaccination within 4 weeks of the first dose of study drug and while on trials is prohibited except for administration of inactivated vaccines. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Patients with another active cancer [excluding basal cell carcinoma, cervical carcinoma in situ or melanoma in situ]. Prior history of other cancer is allowed, as long as there was no active disease within the prior 2 years. * All other unstable, severe, or chronic medical or psychiatric conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, recent (within the past year) or active suicidal ideation or behavior, known alcohol or drug abuse, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Study Objectives The objective of this study is to evaluate the efficacy and safety of DHP107 (Oral paclitaxel) in comparison to Taxol®(IV paclitaxel) in Patients With Metastatic or Recurrent Gastric Cancer After Failure of 1st Line Chemotherapy With Fluoropyrimidine +/- Platinum. Conditions: Stage IV Gastric Cancer Intervention / Treatment: DRUG: Paclitaxel, DRUG: Paclitaxel Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * >=20 years of age * Histologically or cytologically confirmed unresectable, recurrent or metastatic gastric cancer * Failure of a first line therapy with fluoropyrimidine +/- platinum for metastatic or recurrent disease.(Adjuvant chemotherapy is not considered as a first line chemotherapy unless recurrence developed within 6 months of completion of adjuvant therapy.) * Adequate bone marrow, liver and renal functions * INR <= 2.0 * ECOG performance status <= 2 * Neuropathy grade <= 1 * Life expectancy of at least 3 months * Measurable lesion according to RECIST version 1.1 on CT scan * Written informed consent * Patients of child bearing age have to agree to the usage of adequate contraception from before the registration to the study, during the participation period and 90 days after the end of treatment. Female of child bearing age has to show negative for urin pregnancy test within 7 days from beginning of the start of administration. Amenorrhea status has to be sustained for at least 12 months to be considered non-pregnant in case of postmenstrual women. Exclusion Criteria: * Major infectious disease, neurological disorder, or bowel obstruction. * Patients with CNS metastases(confirmed through brain imaging if there are symptoms) * Patient diagnosed with another cancer type (except non-melanoma skin cancer, cervical cancer, or any other cancer that did not recur or metastasized for more than 5 years and considered as complete remission can be registered) * Patient who received radiation therapy within past 2 weeks or who had major surgery including organ resection within past 4 weeks from random assignment date * Patient with the history of failure to the taxane chemotherapy * Patient who need chronic concomitant use of P glycoprotein, immune suppressor, proton pump inhibitor, or H2-receptor antagonist during the period of clinical trial * Chronic treatment using steroid (except oral, local injection, or for externally applied) or other immune suppressor * Patient with myocardial infarction, congestive heart failure, arrhythmia showing abrupt change in the ECG, severe or unstable angina, or other serious heart disease * Patient with other serious internal disease (chronic obstructive or chronic inhibitory lung disease including shortness of breathe at rest due to all reasons, uncontrollable diabetes and hypertension) * History of abuse of a drug or alcohol within 3 months * Lactating or pregnant women, or patient (or spouse) who has no intension of using, or cannot use very effective mean of contraception * Patient who has or is suspected to have problem in bile acid secretion * Patient with active gastrointestinal bleeding, or taking oral anti- vitamine K (With the exception of low dose of Warfarin and acetylsalicylic acide when INR<=2.0) * History of serious hypersensitive reaction to the main ingredient or the excipient of the investigational drug * History of being seropositive for HIV (HIV test is not a prerequisite). * Patients with gastrointestinal dysfunction or on enteral feeding * Other patients who are deemed inadequate to participate in the clinical trial by the investigator

Study Objectives To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy, in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated in patients who have progressed after chemotherapy (Part A) and in patients who have progressed before receiving chemotherapy (Part B). Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off). Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients on a dose and schedule selected from Part A. Conditions: Metastatic Castrate-Resistant Prostate Cancer (mCRPC),, Efficacy,, Safety and Tolerability,, Pharmacokinetics,, Pharmacodynamics,, Tumour Response. Intervention / Treatment: DRUG: Intermittent dosing of AZD5363, DRUG: Intermittent dosing of AZD5363, DRUG: Intermittent dosing of AZD5363 Location: United States, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: SCREENING Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Provision of informed consent * Males aged 18 years and older * Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features for which no standard therapy is currently considered appropriate * Documented evidence of Metastatic Castrate-Resistant Prostate Cancer (mCRPC) * Part A: Patients must have received prior docetaxel-based chemotherapy for mCRPC and have a Circulating Tumour Cell score of 5; * Part B: Patients must have progressed before receiving any chemotherapy for mCRPC; Exclusion Criteria: * Any prior exposure to agents which inhibit AKT as the primary pharmacological activity * Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus * Spinal cord compression or brain metastases unless asymptomatic, treated, and stable and not requiring steroids * Clinically significant abnormalities of glucose metabolism * Major surgery within the previous 4 weeks

Study Objectives Individuals on oral chemotherapy (OC) often face many challenges requiring adequate informational support, monitoring, and management. This pilot randomized control trial (RCT) aims to assess the feasibility, acceptability, and preliminary effects of a comprehensive OC intervention on medication adherence self-efficacy, medication adherence, and symptom distress. Conditions: Oral Chemotherapy Intervention / Treatment: OTHER: Oral chemotherapy information and support Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * 18 years of age or older * Diagnosis of cancer, any stage * Being followed by a care team at the affiliated hospital centre * About to start or within the first cycle of oral anticancer treatment (traditional cytotoxic, targeted therapy, hormonal therapy as active ongoing treatment for cancer with the aim of killing cancer cells/shrinking tumor size) * Has a computer/tablet/smartphone device with internet * The ability to communicate, read, and write in English or French Exclusion Criteria: * Receiving IV chemotherapy, immunotherapy, and/or oral hormonal therapy as long-term maintenance treatment for prevention of cancer's return/growth of cancer cells after initial treatment * Significant physical or cognitive limitations that would prevent ability to participate in study as reported by patient, primary healthcare provider, or research staff * At imminent "end-of-life" * Participating in an ongoing clinical trial

Study Objectives This is a randomized study evaluating the efficacy and impact on function of two different doses of nab-Paclitaxel in elderly patients with advanced breast cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: Nab-paclitaxel 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 confirmed breast cancer, locally recurrent and/or metastatic; any estrogen/progesterone receptor status; HER2 receptor negative OR HER2 positive but with contraindication to anti-HER2 therapy (e.g. known congestive cardiac failure). * Measurable disease or non-measurable but evaluable disease according to RECIST 1.1 criteria * ECOG performance status 0-2 * Estimated life expectancy of >= 12 weeks * No known active/symptomatic CNS metastases * No previous chemotherapy for breast cancer in the advanced setting * Adequate organ function including ( Hemoglobin >= 9g/dL; Absolute neutrophil count >= 1.5 x 10^9/L; Platelets >= 100 x 10^9/L; Bilirubin <= 1.5 mg/dL; ALT and AST <= 3 x ULN (with or without known hepatic metastases); ALP <= 2.5 x ULN; Serum creatinine <= 1.5 ULN or calculated creatinine clearance (CrCl) >= 50mL/min according to the Cockcroft Gault formula * Written informed consent (according to ICH/GCP and national/local regulations) Exclusion Criteria: * Significant peripheral neuropathy (significant peripheral neuropathy is defined as >= grade 2 on CTCAE v4.0 criteria) * Clinically significant comorbidities including: uncontrolled cardiac arrhythmias (except rate-controlled atrial fibrillation), NYHA class III or IV cardiac failure, uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity * Other malignancy within the last 5 years, except for adequately treated non-melanomatous skin cancers, cervical intraepithelial neoplasia or cervical carcinoma in situ * Intake of any concomitant medications or therapies that may potentially interact with the trial agent. Any prohibited medication must be discontinued at least 14 days prior to trial entry * Presence of any psychological, familial, sociological or geographical condition that may potentially hamper compliance with the study protocol and follow-up schedule; these conditions should be discussed with the patient before trial registration

Study Objectives This early phase IIA trial studies how well celecoxib, recombinant interferon alfa-2b, and rintatolimod work in treating patients with colorectal cancer that as spread to the liver. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Recombinant interferon alfa-2b is a substance that can improve the body's natural response and may interfere with the growth of tumor cells. Rintatolimod may stimulate the immune system. Giving celecoxib, recombinant interferon alfa-2b, and rintatolimod may work better at treating colorectal cancer that has spread to the liver. Conditions: Metastatic Carcinoma in the Liver, Recurrent Colorectal Carcinoma, Stage IV Colorectal Cancer AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7 Intervention / Treatment: DRUG: Celecoxib, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Recombinant Interferon Alfa-2b, DRUG: Rintatolimod 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: * Recurrent and/or metastatic unresectable colorectal cancer with hepatic metastases * Hepatic metastases present which are amenable to biopsy * Prior treatment with, contra-indication to or refusal of a fluoropyrimidine, irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wild-type [wt]) as well as a PD-1 or PD-L1 targeted drug if MSI-H/dMMR * No chemotherapy, radiotherapy, major surgery, or biologic therapy within 3 weeks of protocol treatment * An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Have measurable disease per RECIST 1.1 criteria present * Ability to swallow and retain oral medication * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Platelet >= 75,000/uL * Hemoglobin >= 9 g/dL * Hematocrit >= 27% * Absolute neutrophil count (ANC) >= 1500/uL * Creatinine < = institutional upper limit of normal (ULN) OR * Creatinine clearance >= 50 mL/min for patients with creatinine levels greater than ULN * Total bilirubin =< 1.5 X institutional ULN or for patients with known Gilbert's Syndrome total bilirubin <= 3 x ULN * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN * Plasma amylase =< 1.5 X institutional ULN * Lipase =< 1.5 X institutional ULN * Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment * Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation * Patients who are pregnant or nursing; women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening * Untreated central nervous system (CNS) metastases * Cardiac risk factors including: * Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent * Patients with a New York Heart Association classification of III or IV * History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; patients with ulceration, bleeding or perforation in the lower bowel are not excluded * Prior allergic reaction or hypersensitivity to celecoxib, or non-steroidal antiinflammatory drugs (NSAIDs) or any study agents which would prevent completion of protocol therapy * Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average; low-dose aspirin not exceeding 100 mg/day is permitted; patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required * Received an investigational agent within 30 days prior to enrollment * Unwilling or unable to follow protocol requirements * Patients with known serious mood disorders * Any additional condition which in the investigator?s opinion deems the participant an unsuitable candidate to receive the study drugs

Study Objectives In this phase II trial, we plan to evaluate the combination of Tarceva and Avastin in the treatment of patients with metastatic renal cell carcinoma. This trial will be one of the first phase II trials to evaluate a combination of targeted agents in the treatment of a common solid tumor with a strong biologic rationale based on Cancer Biology (VHL/HIF/VEGF/EGFr). Conditions: Kidney Cancer Intervention / Treatment: DRUG: OSI-774, 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: To be included in this study, you must meet the following criteria: * Metastatic or unresectable clear cell kidney cancer confirmed by biopsy * Previous nephrectomy * Maximum of 1 previous regimen for metastatic disease * Ability to perform activities of daily living with minimal assistance * Measurable disease * Adequate bone marrow, liver and kidney function * Give written informed consent prior to study entry Exclusion Criteria: You cannot participate in this study if any of the following apply to you: * Age < 18 years * Treatment with more than one previous regimen for metastatic disease * Clinically significant cardiovascular disease * Active brain metastases * History of CNS disease * Clinical history of coughing or vomiting blood. * History of thromboembolic disease. * PEG or G-tube are ineligible. * Current use of full dose anticoagulants or thrombolytic agents * Chronic daily treatment with aspirin or NSAIDS * Any clinical evidence or history of a bleeding or clotting disorder Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Study Objectives This phase II trial is studying erlotinib to see how well it works in treating patients with persistent or recurrent cancer of the cervix. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor Conditions: Cervical Squamous Cell Carcinoma, Recurrent Cervical Cancer Intervention / Treatment: DRUG: erlotinib hydrochloride, 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 confirmed squamous cell carcinoma (SCC) of the cervix * Persistent or recurrent progressive disease * At least 1 prior systemic chemotherapy regimen for management of advanced, metastatic, or recurrent SCC of the cervix is required * Chemotherapy administered as a radiosensitizer in conjunction with radiotherapy does not count as a systemic chemotherapy regimen * At least 1 unidimensionally measurable target lesion * At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan * Lesions within a previously irradiated field are considered nontarget lesions unless disease progression or persistence is confirmed >= 90 days after completion of radiotherapy * Tumor accessible for repeat needle biopsy * Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (any active GOG phase III protocol for the same patient population) * Performance status - GOG 0-2 (for patients who have received only 1 prior regimen) * Performance status - GOG 0-1 (for patients who have received 2 prior regimens) * Platelet count at least 100,000/mm^3 * Absolute neutrophil count at least 1,500/mm^3 * Bilirubin no greater than upper limit of normal (ULN) * SGOT no greater than 2.5 times ULN * Alkaline phosphatase no greater than 2.5 times ULN * Creatinine no greater than 1.5 times ULN * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No abnormalities of the cornea (e.g., dry eye syndrome or Sjogren's syndrome) * No congenital abnormalities (e.g., Fuch's dystrophy) * No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) * No abnormal corneal sensitivity test (Schirmer test or similar tear production test) * No other invasive malignancy within the past 5 years except nonmelanoma skin cancer * No uncontrolled concurrent illness * No ongoing or active infection requiring IV antibiotics * No psychiatric illness or social situation that would preclude study compliance * No grade 2 or greater sensory or motor neuropathy * No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * At least 3 weeks since prior immunologic therapy for SCC of the cervix * One additional prior cytotoxic chemotherapy regimen for recurrent or persistent disease allowed * At least 3 weeks since prior chemotherapy for SCC of the cervix and recovered * No prior non-cytotoxic chemotherapy for recurrent or persistent disease * At least 3 weeks since prior hormonal therapy for SCC of the cervix * At least 3 weeks since prior radiotherapy for SCC of the cervix and recovered * Recovered from recent prior surgery * At least 3 weeks since other prior therapy for SCC of the cervix * No prior epidermal growth factor receptor-targeting therapies * No prior anticancer treatment that would preclude study participation * No other concurrent investigational or commercial agents or therapies for SCC of the cervix

Study Objectives To evaluate the major molecular response (MMR) rate at 12 months of nilotinib treatment on study in patients with Philadelphia Chromosome Positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have a suboptimal molecular response to imatinib at 18 months or later. Conditions: Philadelphia Chromosome Positive, Chronic Myelogenous Leukemia in Chronic Phase Intervention / Treatment: DRUG: Nilotinib Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female patients >= 18 years of age. * ECOG 0, 1, or 2. * Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy. * Patients with suboptimal molecular response to imatinib treatment continued for at least 18 months (first line therapy) Suboptimal molecular response defined as all of the following conditions: 1. Patients who have achieved CCyR (0% Ph+ chromosomes). 2. Patients who don't achieve MMR (MMR defined as BCR-ABL/ABL ratio of <= 0.1% on the International Scale as detected by RQ-PCR). The treatment with imatinib defined as: Dose of 300 mg or higher daily must be maintained for a minimum of 3 months prior to study entry. * Patients who meet the following laboratory tests criteria: 1. total bilirubin < 1.5 x ULN, 2. SGOT and SGPT < 2.5 x ULN, 3. creatinine < 1.5 x ULN, 4. Serum amylase and lipase <= 1.5 x ULN, 5. Alkaline phosphatase <= 2.5 x ULN unless considered tumor related. 6. Serum potassium, phosphorus, magnesium and calcium >= LLN or correctable with supplements prior to the first dose of study drug. * Written informed consent prior to any study related screening procedures being performed. Exclusion Criteria: * Prior accelerated phase or blast crisis CML. * Previously documented T315I mutations. * Presence of chromosomal abnormalities other than Ph+. * Previous treatment with any other tyrosine kinase inhibitor except imatinib. * Impaired cardiac function including any one of the following: 1. Complete left bundle branch block 2. Congenital long QT syndrome or family history of long QT syndrome 3. History of or presence of significant ventricular or atrial tachyarrhythmias 4. Clinically significant resting brachycardia (<50 bpm) 5. QTcF > 450 msec on screening ECG 6. Use of a ventricular-paced pacemaker 7. Myocardial infarction during the last 12 months 8. Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina). * Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St John's Wort), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. See Section 6.4.3 for complete list of these medications.

Study Objectives This is a phase I open label study to evaluate safety and efficacy of P1446A-05 in subjects with advanced refractory malignancies. Subjects of solid tumors or hematologic malignancies will be included. This is a dose escalation study following an accelerated titration design. It is expected that around 50 subjects would be enrolled in the study.Safety assessment will be conducted on the basis of vital signs, physical examination and laboratory investigations undertaken at regular intervals as per the schedule. Conditions: Solid Tumor, Hematologic Malignancy Intervention / Treatment: DRUG: P1446A-05 Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Subjects must have histologically and/ or cytologically confirmed solid malignant tumor or hematologic malignancy that is refractory to currently available treatment or for which no standard treatment exists * Subjects of either sex and more than or equal to 18 years of age * ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2 * Subjects with life expectancy of at least 4 months * Hemoglobin greater than or equal to 8 g/dl * Absolute neutrophil count greater than or equal to 1000/mm3 * Platelet count greater than or equal to 50,000/ mm3 * Total bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN) * AST/ALT less than or equal to 3 X institutional upper limit of normal (ULN) * Creatinine less than or equal to 1.5 X institutional upper limit of normal (ULN) * Ability to understand and willingness to sign a written informed consent document. Exclusion criteria * Subjects who have received radiotherapy, chemotherapy or biologic/targeted anticancer agents within 4 weeks prior to day 1 of study drug administration (6 weeks for nitrosoureas or mitomycin C) or have not recovered completely from adverse effects of any prior radiotherapy, chemotherapy or biologic/targeted agents * Subjects who have received autologous or allogeneic bone marrow transplant within 6 months of day 1 of study drug administration * Subjects with known brain metastases at the time of screening * Subjects who had received any other investigational drug within 1 month or within five half-lives of the other investigational agent, whichever is longer prior to day 1 of study drug administration or who have not completely recovered from adverse effects of the investigational agent received prior to this period. * History of allergic reactions attributed to compounds of similar chemical structure to P1446A-05. * Subjects on immunosuppressive therapy. * History of unstable angina or myocardial infarction or stroke within previous 6 months. * Subjects with uncontrolled inter-current illness including, but not limited to active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B. * History of any other prior malignancy except for curatively treated basal cell or squamous cell carcinoma of skin, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or any other cancer for which the subject has been diseasefree for at least 3 years. * Women who are pregnant or lactating. * Women of childbearing potential [defined as a sexually mature woman who has not undergone hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e. who has had menses any time in the preceding 24 consecutive months)] and men, not agreeing to use adequate contraception (e.g., hormonal or barrier method of birth control or abstinence) prior to study entry (after signing the informed consent document), during the duration of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilised. * Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at an unacceptable risk or deems the subject not suitable for participation in the study.

Study Objectives The purpose of this clinical study is to determine the effectiveness (ability to provide beneficial treatment of the disease) and safety of pralatrexate compared to erlotinib when given to non-small cell lung cancer (NSCLC) patients who are current or former cigarette smokers and who have received at least 1 prior treatment with a platinum drug (cisplatin or carboplatin) Conditions: Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Pralatrexate, DRUG: Erlotinib, DIETARY_SUPPLEMENT: Vitamin B12, DIETARY_SUPPLEMENT: Folic Acid Location: Hungary, India, Brazil, United States, Czechia, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Confirmed Stage IIIB/ IV non-small cell lung cancer (NSCLC). * Relapsed after treatment with 1 or 2 prior chemotherapy regimens, including at least 1 platinum-based treatment. Patients may have received pemetrexed as 1 of the prior therapies. Patients may not have received investigational therapy as their only prior therapy. * Recovered from the toxic effects of prior therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Smoked >= 100 cigarettes in their lifetime, whether a former or current cigarette smoker. * Adequate blood, liver and kidney function as defined by laboratory values. * Received 1-1.25 mg daily oral folic acid for at least 7 days prior to randomization and 1 mg intramuscular injection of vitamin B12 within 10 weeks prior to randomization. * Women of childbearing potential must use medically acceptable birth control and have a negative serum pregnancy test within 14 days prior to randomization. Patients who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized do not require this test. * Men who are not surgically sterile must use medically safe and effective birth control from the time of study randomization, and agree to continue practicing until at least 90 days after the last administration of study treatment. * Accessible for repeat dosing and follow-up. * Give written informed consent. Exclusion Criteria: * Active concurrent primary malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix). If there is a history of prior malignancy, the patient must be disease-free for >= 5 years. Patients with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no evidence of active or recurrent disease. * Use of investigational drugs, biologics, or devices within 4 weeks prior to randomization. * Previous exposure to pralatrexate or erlotinib. * Women who are pregnant or breastfeeding. * Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA) Functional Classification. * Uncontrolled hypertension. * Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of <100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy. * Symptomatic central nervous system metastases or lesions for which treatment is required. * Major surgery within 2 weeks of study randomization. * Receipt of any conventional systemic chemotherapy within 4 weeks (6 weeks for nitrosoureas, mitomycin C), or radiation therapy (RT) within 2 weeks, prior to randomization. * Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment. * Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent or limit study compliance.

Study Objectives An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML). Conditions: Acute Myeloid Leukemia (AML) Intervention / Treatment: DRUG: Venetoclax, DRUG: Alvocidib Location: United States, United Kingdom, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Must have adequate coagulation, hematology, kidney, and liver function, per protocol. * Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) * Meet the following disease activity criteria: * an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and * an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. * If male participant is sexually active, he must agree from day 1 through 6 months after the last dose of alvocidib or 90 days after the last dose of venetoclax, whichever is longer, to practice the protocol-specified protection. Exclusion Criteria: * History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ. * Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy. * History of previous enrollment in Studies NCT02993523 or NCT03069352. * History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor. * History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.

Study Objectives The incidence of non-Hodgkin's lymphoma (NHL) is steadily increasing worldwide. At present, it is the sixth most commonly diagnosed cancer in France, with 10 000 estimated new cases and 5200 deaths annually. An increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence during last 40 years. This rise has been noted worldwide, particularly in elderly persons \>55 years. Increases in high-grade NHL and extranodal disease are predominant. There is about 80% of B-cell histology, approximately 90% of follicular lymphomas and about 70% of aggressive lymphoma patients present with disseminated disease at diagnosis. The prognosis of NHL depends on the histological type, stage and treatment. Indolent lymphomas have a relatively good prognosis with survival time as long as 10 years, but they are usually incurable in advanced stages. Aggressive NHL constitutes about 50% of all cases of NHL in Western Europe. Approximately 50 - 60% of these patients can be cured with immuno-chemotherapy regiments. Subsequently, almost 50% of patients will eventually relapse or become refractory to treatment. The prognosis for patients with refractory or relapsed aggressive NHL is generally poor. The response rates to salvage therapy regimens range from 20 to 40%. Patients who present with refractory disease have the worst prognosis, with a median survival of less than six months. Only a minority of patients can be given high dose chemotherapy, the majority being ineligible due to disease progression. By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with mabthera (rituximab) resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma. As concerns the timing of administration and doses of medications, phase I/II studies are ongoing with R-CHOP in combination with Revlimid (Lenalidomide) in DLBCL. The latest presentation is by Nowakowski et al. at ASCO meeting in June 2010. This study determined the maximum tolerated dose of Revlimid(Lenalidomide)administered on days 1-10 with standard R-CHOP (R2-CHOP). NO DLT was found and 25 mg of Revlimid(Lenalidomide)was the recommended dose for phase II with enrollment of 32 patients. These encouraging results permit to introduce in our much less toxic protocol 25 mg of Revlimid(Lenalidomide)as initial dose, with progressive reduction in case of toxicity. As regards the dose and timing of Mabthera(Rituximab), in DLBCL it was traditionally used as a single 375 mg/m2 injection/cycle. Pre-clinical data suggests that for the optimal NK enhancement Revlimid(Lenalidomide)must be administrated several days (approx. 7 days) before Mabthera(Rituximab)injection. So, our protocol provides Mabthera(Rituximab)IV administration at day 7 of Revlimid(Lenalidomide). Performed parallel biological investigation of NK status will permit to confirm this hypothesis with possible correction of timing and number of administrations of Mabthera(Rituximab)par cycle. Conditions: Non-Hodgkin Lymphoma Intervention / Treatment: DRUG: Lenalidomide/Rituximab Location: France 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. * Diagnosis of relapsed or refractory to previous therapy biopsy-proven Diffuse Large B cell non-Hodgkin's Lymphoma (there is no limit on the number of prior therapies. Subjects who have relapsed following an autologous stem cell transplant are eligible.) * Measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter. * ECOG (Eastern Cooperative Oncology Group) performance status score of 0, 1, or 2. * Life expectancy of >= 90 days (3 months). * Must be able to adhere to the study visit schedule and other protocol requirements. * Signed informed consent * Social security program affiliation * Females of childbearing potential (FCBP*) must have negative pregnancy test (sensitivity of at least 25 mIU/mL) prior to starting study drug in accordance with the Global Pregnancy Prevention Plan (PPP, annex 6) * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously** or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study drug; and 3) for at least 12 months after discontinuation from the study drug. Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy. Agree not to donate blood, semen or sperm while taking study drug and for 28 days after stopping study drug. Do not share drug with other person. Do not break, chew, or open study drug capsules. Return unused study drug capsules to the study doctor. EXCLUSION criteria * Any of the following laboratory abnormalities: * Absolute neutrophil count (ANC) < 1.5 x 109/L. * Platelet count < 60 x 109/L. * Calculated creatinine clearance (Cockcroft-Gault formula) of < 50mL/min. * Serum SGOT/AST or SGPT/ALT 5.0 x upper limit of normal (ULN). * Serum total bilirubin > 2.0 mg/dL (34 μmol/L)/conjugated bilirubin >0.8mg/dL, except in case of hemolytic anemia. * Subjects who are candidates for and willing to undergo an autologous stem cell transplant. * Subjects who are post allogenic stem cell transplant. * All subjects with active central nervous system (CNS) lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible. (If required, lumbar puncture, CT or MRI should be performed during screening process.) Subjects should not be receiving corticosteroids. * Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for 5 years * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or lactating females. * Uncontrolled intercurrent illness including, but not limited to: * Ongoing, severe or active infection requiring antibiotics. * Uncontrolled diabetes mellitus as defined by the investigator. * Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease). * Unstable angina pectoris, angioplasty, stenting, or myocardial infarctions within 168 days (6 months). * Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia. * Prior >= Grade 3 allergic reaction/hypersensitivity to thalidomide. * Prior >= Grade 3 rash or any desquamating (blistering) rash while taking thalidomide. * Subjects with >= Grade 2 neuropathy. * Prior use of lenalidomide. * Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy. * Known active Hepatitis B or C. * Known positive for HIV. * Known hypersensibility to Rituximab or excipients, or to murine proteins, * Patients with severe immune deficit

Study Objectives Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to learn if thiotepa, busulfan, and clofarabine, when given before an allogeneic (bone marrow , blood, or cord blood cells) or haploidentical (bone marrow) stem cell transplantation can help to control cancers of the bone marrow and lymph node system. The safety of this treatment will also be studied. This is an investigational study. Thiotepa and clofarabine are FDA approved and commercially available for the treatment of leukemia. Busulfan is FDA approved and commercially available for use in stem cell transplantation. The combination of thiotepa, clofarabine, and busulfan together with a stem cell transplant is investigational. Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson. Conditions: Stem Cell Transplantation, Leukemia, Lymphoma Intervention / Treatment: DRUG: Thiotepa, DRUG: Clofarabine, DRUG: Busulfan, PROCEDURE: Allogeneic Stem Cell Transplantation, DRUG: Thymoglobulin (ATG), DRUG: G-CSF (Filgrastim), DRUG: Tacrolimus, DRUG: Methotrexate, DRUG: Cyclophosphamide, DRUG: Mesna 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: * Diagnosed with one of the following diseases: * Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission, or CR1 considered at risk for relapse * Myelodysplastic syndromes with International Prognostic Scoring System score (IPSS score) >= 2 or myelodysplasia that has not responded to chemotherapy * Biphenotypic leukemia * Acute lymphocytic leukemia with induction failure, first complete remission with high risk cytogenetics (e.g. Philadelphia positive chromosome, t(4:11) Remission requiring more than 2 chemotherapy to achieve remission, or any stage beyond CR1 * Chronic Myelogenous Leukemia (CML): second chronic phase, accelerated phase or blast crises with less than 10% blasts in the bone marrow, or CR1 and resistance to Gleevec or other tyrosine kinase inhibitors * Non-Hodgkin's Lymphoma - induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant) * Hodgkin's disease - induction failure, second or later complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). * Chronic Lymphocytic Leukemia that has failed induction therapy or Rai Stages 2-4 * Related or unrelated donor which is HLA-matched or mismatched in 1 HLA A, B, C, DR, or DQ locus is acceptable (i.e. >= 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current std. for BMT program). Cord blood units must match patient at 4, 5, or 6/6 HLA class 1 serological & II molecular antigens with a min. of 2 x 10e7 TNC/kg recipient weight in the pre-thawed fraction. For patient lacking a matched related or unrelated donor or acceptable cord blood unit(s), a related haploidentical donor (<= 7/8 allele matched at A, B, C, DR loci) may be used. * Age <= 60 years. * Lansky performance score >= 50% for patients <= 16 years of age, or Zubrod performance status score of 0-2 for patients > 16 years of age. * Cardiac function - left ventricular ejection fraction >= 40%. * Pulmonary function - diffusion capacity of at least 50% predicted. Children unable to perform pulmonary function tests (e.g. less than 7 years old) pulse oximetry of >= 92% on room air. * Serum creatinine < 1.6 mg/dL or creatinine clearance >= 50 ml/min. * SGPT <= 200 IU/mL, serum bilirubin < 1.5 x normal. * Written informed consent and assent as is age appropriate. * No active infection. Exclusion Criteria: * Pregnancy in women of child bearing potential (pregnancy test performed within 2 weeks of study entry). * HIV positive (highly immunosuppressive treatment) * Active CNS leukemia * Chronic or active Hepatitis B or Hepatitis C. If questions about liver health discuss with PI and strongly consider liver biopsy.

Study Objectives The malignancies (advanced solid tumors) that have been chosen for evaluation of E7389 are those where E7389 has demonstrated significant pre-clinical anti-tumor activity, both in vitro and in vivo. The ultimate goal is to demonstrate the clinical activity of E7389 in the treatment of these, and potentially other, tumor types. Conditions: Cancer Intervention / Treatment: DRUG: E7389 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 have a histologically or cytologically confirmed and measurable advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy) * Patients may have received prior chemotherapy (limit of two prior chemotherapy regimens) * Patients must be aged >= 18 years * Patients must have a Karnofsky Performance Status of > 70% -- Patients must have a life expectancy of > 3 months * Patients must have adequate renal function as evidenced by serum creatinine <1.5 mg/dL or creatinine clearance > 60 mL/minute * Patients must have adequate bone marrow function as evidenced by absolute neutrophil count > 1,500/µL and platelets > 100,000/µL * Patients must have adequate liver function as evidenced by bilirubin < 1.5 mg/dL and alanine transaminase (ALAT) and aspartate transaminase (ASAT) < 2 times the upper limits of normal * Patients must be willing and able to comply with the study protocol for the duration of the study * Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice. Exclusion Criteria: * Patients who have received chemotherapy within three weeks (six weeks if nitrosoureas were received) of E7389 treatment start * Patients who have not recovered from any chemotherapy related or other therapy related toxicity at study entry * Patients who require therapeutic doses of anti-coagulant therapy (eg, Coumadin, heparin, low molecular weight heparin). Low doses of anticoagulants used for patency (e.g., lines, catheters, ports) are permitted. * Women who are pregnant or breastfeeding. * Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) * Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception * Patients who have not successfully completed local therapy for previously treated central nervous system (CNS) metastases and who have not been discontinued from corticosteroids for at least four weeks before starting treatment with E7389. Patients with asymptomatic brain metastases who have no evidence of midline shift on CT scan or MRI may be enrolled without initiation of local therapy for the CNS metastases. In this case, a repeat scan must be performed within four weeks of the original scan to ensure that disease progression is not occurring. * Patients who have tested positive for HIV * Patients with severe uncontrolled intercurrent illness/infection (excluding malignancies) * Patients with cardiovascular impairment * Patients with organ allografts * Patients who have received investigational drugs, including immunotherapy, gene therapy, hormone therapy, or other biologic therapy; anti-neoplastic therapy; or radiation therapy (other than required for palliation) within three weeks of E7389 treatment start * Patients who have had major surgery within four weeks of E7389 treatment start without a full recovery * Patients with a hypersensitivity to Halichondrin B and/or Halichondrin B-like compounds Patients with other significant disease that, in the Investigator's opinion, would exclude the patient from the study

Study Objectives The purpose of this research study is to test the safety and tolerability of the combination treatment of the investigational drugs vorinostat and pembrolizumab, in combination with chemotherapy (temozolomide), and radiotherapy. The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for use to treat a deadly skin cancer called melanoma and lung cancer and vorinostat to treat some forms of blood and lymph node cancers. However, both vorinostat and pembrolizumab are considered investigational drugs in this study because they are not approved for treatment of glioblastoma. Conditions: Glioblastoma, Brain Tumor, GBM Intervention / Treatment: DRUG: Pembrolizumab, DRUG: Vorinostat, DRUG: Temozolomide, RADIATION: Radiotherapy 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: * Newly diagnosed glioblastoma or gliosarcoma * Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma * An interval of >= 21 days since surgical resection prior to treatment on the trial * Karnofsky performance status of 70 or higher * Adequate organ function laboratory values * Resting baseline O2 saturation by pulse oximetry of >= 92% at rest * Willing and able to provide written informed consent/assent for the trial. * Life expectancy >= 12 weeks * Willingness to discontinue medications known to be associated with risk of Torsades de Pointes such as quinidine, procainamide, disopyramide, amiodarone, erythromycin, clarithromycin, chlorpromazine and haloperidol * Single lesion < 4 cm in longest diameter (diameter of enhancing lesion) * Patient shouldn't have received any anti-cancer therapy for glioblastoma in past * Females of childbearing potential (FOCBP) should have a negative urine or serum pregnancy 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. * Females and males of childbearing potential must be willing to use an adequate method of contraception per protocol for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for participant. * Use of Optune device is allowed. Exclusion Criteria: * Had prior treatment of glioblastoma (GBM) with radiation and temozolomide * Has evidence of leptomeningeal disease * Had prior treatment with Gliadel * Unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain * 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 or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (<= 2 mg/day dexamethasone equivalents) by the time of first dose of treatment are allowed. * Has a known history of active Bacillus Tuberculosis (TB) * Hypersensitivity to pembrolizumab 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: Potential participants with <= Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If patient 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 or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * 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. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. * Has known history of, or any evidence of active, interstitial lung disease or non-infectious pneumonitis requiring corticosteroid therapy * Has an active serious infection requiring systemic therapy * Had major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to day 1 of treatment on study * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate * 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, 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. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Study Objectives The purpose of this phase II, randomized, open-label clinical trial is to study 2 schedules of single-agent Irinotecan in women with metastatic breast cancer who have experienced failure of prior therapy with an anthracycline, a taxane, and capecitabine. Patients will receive Irinotecan capsules either once each day for 5 days, or once a day for 14 days in 3 week cycles. Conditions: Breast Neoplasms Intervention / Treatment: DRUG: Irinotecan Location: New Zealand, United States, Australia, Colombia, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Women with diagnosis of primary adenocarcinoma of the breast * Presence of locally advanced or metastatic disease non-amenable to surgery or radiation therapy with curative intent * At least one measurable lesion >20mm (or >10 mm with spiral CT scan) * Must have received (and failed) prior treatment with an anthracycline, a taxane, and capecitabine in the adjuvant and/or advanced disease treatment setting * Women at least 18 years old, with performance status 0-2 Exclusion Criteria: * Prior treatment with another topoisomerase I inhibitor * Current enrollment in another clinical trial

Study Objectives This clinical trial is about testing GO-203-2c, which is a newly discovered compound that binds to an oncoprotein (a cancer causing protein) called MUC1 (which is over-expressed in many cancers). By binding to MUC1, GO-203-2c eventually causes tumor cell death in laboratory studies. This study is being done to: * Test the safety of GO-203-2c and see what effects (good and bad) it has on you and your cancer * Find the highest dose of GO-203-2c that can be given without causing bad side effects * Examine how much GO-203-2c is in the blood at certain times after it is given and how quickly the body gets rid of it * Observe whether there is any effect of GO-203-2c on the size and activity of cancer in your body Conditions: Solid Tumors Intervention / Treatment: DRUG: GO-203-2c Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed solid tumors or lymphomas * Tumor progression observed after receiving standard/approved systemic chemotherapy and/or immunotherapy including monoclonal antibodies, or when there is no approved or effective therapy * One or more measureable tumors by radiological evaluation * Karnofsky performance >= 70% * Life expectancy of >= 3 months * Age >= 18 years * Signed, written IRB-approved informed consent * Negative pregnancy test (if female) * Adequate liver function: * Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) * AST (SGOT), ALT (SGPT) and Alkaline phosphatase less than or equal to 2.5 x ULN (if liver metastases are present, then less than or equal to 5 x ULN is allowed) * Adequate renal function: * Serum creatinine within normal limits, OR calculated creatinine clearance >= 60 mL/min/1.73 m2 for patients with serum creatinine above institutional ULN. * Corrected serum calcium >= lower limit of the institutional normal range (LLN) * Serum phosphorus level >= LLN * Adequate hematologic function: * Absolute Neutrophil Count >= 1500 cells/mm3 * Platelet count >= 100,000 (cells/mm3) * Hemoglobin >= 9 g/dL * Urinalysis: * No clinically significant abnormalities * Adequate coagulation function: * PT <= 1.25 x ULN * PTT <= 1.25 x ULN * For men and women of child-producing potential, agreement to use effective contraceptive methods during the study Exclusion Criteria: * New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG * Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy * Pregnant or nursing women. NOTE: Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. * Major surgery within 4 weeks prior to Day 1, or not fully recovered by Day 1 * Minor surgery within 2 weeks prior to Day 1, or not fully recovered by Day 1 * Treatment with radiation therapy within 4 weeks prior to Day 1. * Received systemic chemotherapy or monoclonal antibody or other immunotherapy within 4 weeks prior to Day 1 (exceptions: 6 weeks for nitrosourea, mitomycin C, or any agent with a known treatment effect > 4 weeks' duration), or not fully recovered from any side effects from previous therapy by Day 1 * History of allergic reactions attributed to excipients or chemical products used in the final GO-203-2c drug formulation * Known infection with HIV, hepatitis B, or hepatitis C. * Subjects with risk factors for gastrointestinal perforation or pulmonary hemorrhage (e.g. unresected luminal intestinal cancers; abdominal carcinomatosis within 3 months before the first dose of study drug, abdominal fistula, acute diverticulitis, peptic ulcer disease, irritable bowel syndrome, Crohn's disease, pulmonary hemorrhage, hemoptysis, or tuberculosis) * Currently receiving or having received treatment with any other investigational agent within 4 weeks prior to Day 1, or not fully recovered from toxicities of prior treatment by Day 1 * Serious and/or poorly controlled non-malignant disease (including but not limited to, ongoing or active infection, hydronephrosis, hypertension, diabetes, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the sponsor. Patients with such conditions should be discussed with the Medical Monitor prior to enrollment. All medical conditions must be NCI CTCAE Grade 1 or lower at baseline. * Unwillingness or inability to comply with requirements of this protocol

Study Objectives Chemotherapy can often cause anemia in patients with cancer. Anemia is a low number of red blood cells. The symptoms of anemia may include fatigue, dizziness, headache, chest pain, and shortness of breath. Erythropoietin is a hormone made by the kidneys that signals the bone marrow to produce more red blood cells. Recombinant human erythropoietin has been produced in the laboratory and has the same effect as the hormone produced by the body. Use of recombinant human erythropoietin allows the body to produce more red blood cells, possibly eliminating or decreasing your symptoms and the need for a red blood cell transfusion. Recombinant human erythropoietin is FDA approved to treat anemia in cancer patients receiving chemotherapy. This clinical study is investigating the effectiveness of darbepoetin alfa for the treatment of anemia in patients with non-myeloid malignancies who are receiving multicycle chemotherapy. Darbepoetin alfa is a recombinant erythropoietic protein that stimulates the production of red blood cells. This medication has not been approved to treat cancer patients with anemia, however it has been approved by the FDA to treat chronic renal failure patients with anemia. Conditions: Neoplasms, Anemia Intervention / Treatment: DRUG: Darbepoetin alfa, DRUG: rHuEPO Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Men or women of legal age, diagnosed with a non-myeloid malignancy and scheduled to receive at least 12 additional weeks of cyclic cytotoxic chemotherapy from the time of first dose of study drug * Screening hemoglobin concentration less than or equal to 11.0 g/dL * ECOG performance status of 0 to 2 (inclusive) Exclusion Criteria: * History of seizure disorder * Primary hematologic disorder that could cause anemia * Unstable or uncontrolled disease/condition related to or affecting cardiac function * Clinical evidence of chronic infection/inflammatory disease * Positive test for HIV infection * Previously confirmed neutralizing antibodies to rHuEPO * Received rHuEPO or darbepoetin alfa therapy within 4 weeks of study day 1 or more than 2 RBC transfusion occurences

Study Objectives Previous studies provide a strong theoretical rationale for the conduct of a randomized study evaluating the efficacy and safety of Herceptin and pertuzumab in combination with FLOT in the perioperative treatment of resectable HER-2 positive adenocarcinoma of the stomach or GEJ. Conditions: Stomach Cancer, Gastroesophageal Junction Cancer Intervention / Treatment: DRUG: FLOT alone, BIOLOGICAL: FLOT + Herceptin/Pertuzumab Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically confirmed adenocarcinoma of the GEJ (type I-III) or the stomach (uT2, uT3, uT4, any N category, M0), or any T N+ M0 patient, with the following specifications: * Medical and technical operability * Centralized detection of either an adenocarcinoma with HER-2 3+ (IHC) or HER-2 2+ (IHC) with amplification proven by FISH, SISH or CISH * No preceding cytotoxic or targeted therapy * No prior partial or complete tumor resection * Exclusion of the infiltration of any adjacent organs or structures by CT or MRI * Exclusion of distant metastasis by CT or MRI of thorax and abdomen, and bone scan (if osseous lesions are suspected due to clinical signs) * Female and male patients >= 18 years. Patients in reproductive age must be willing to use adequate contraception during the study and for 7 months after the end of pertuzumab and Herceptin treatment (Appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start. * ECOG <= 2 * Laparoscopic exclusion of peritoneal carcinomatosis, if suspected clinically * Adequate haematological, hepatic and renal function parameters: * Leukocytes >= 3.000/mm³, platelets >= 100.000/mm3 * Serum creatinine <= 1.5 x upper limit of normal, or GFR > 40 ml/min * Bilirubin <= 1.5 x upper limit of normal, AST and ALT <= 3.5 x upper limit of normal, alkaline phosphatase <= 6 x upper limit of normal * LVEF value > 55 %, as assessed by echocardiography * Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures Exclusion Criteria: * Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastasis!) * Known hypersensitivity against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel * Other known contraindications against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin, or docetaxel * Documented history of congestive heart failure of any NYHA, myocardial infarction within the past 6 months before the first dose of study treatment * Clinically significant valvular defect , history of poorly controlled arterial hypertension (systolic blood pressure > 180 mmHG or diastolic blood pressure > 100 mmHg) or uncontrollable high-risk cardiac arrhythmia (i.e tachycardia with a heart rate > 100/min at rest), significant ventricular arrhythmia (ventricular tachycardia) or higher grade atrioventricular-block (second degree AV-block Type 2 (Mobitz2) or third degree AV-block) * Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix * Known brain metastases * Other severe internal disease or acute infection * Peripheral polyneuropathy >= NCI Grade II * Chronic inflammatory bowel disease * Clinically significant active GI bleeding * On-treatment participation in another clinical study in the period 30 days prior to inclusion and during the study * Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. * Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4) * Any other concurrent antineoplastic treatment including irradiation

Study Objectives This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell transplant works in treating patients with hematologic cancer or bone marrow failure disorders. Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect) Conditions: Accelerated Phase Chronic Myelogenous Leukemia, Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Aplastic Anemia, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, Childhood Myelodysplastic Syndromes, Childhood Nasal Type Extranodal NK/T-cell Lymphoma, Chronic Eosinophilic Leukemia, Chronic Myelomonocytic Leukemia, Chronic Neutrophilic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Fanconi Anemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Paroxysmal Nocturnal Hemoglobinuria, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Splenic Marginal Zone Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma, Waldenström Macroglobulinemia Intervention / Treatment: DRUG: fludarabine phosphate, DRUG: melphalan, RADIATION: total-body irradiation, PROCEDURE: allogeneic hematopoietic stem cell transplantation, BIOLOGICAL: anti-thymocyte globulin 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: * Diagnosis of a histology documented hematologic malignancy or marrow disorder * Bone marrow failure disorders and other non-malignant hematologic or immunologic disorders: * Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH): * Primary allogeneic hematopoietic stem cell transplantation (HSCT) is appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available * Patients with PNH must have a history of thrombosis related to PNH * Hereditary bone marrow failure disorders include Fanconi anemia or related chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic thrombocytopenia: * Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable * Dyskeratosis: diagnosis is supported by using either telomerase reverse transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or Xlinked DKC1 gene mutation * Other non-malignant hematologic or immunologic disorders that require transplantation * Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia) * Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia) * Congenital primary immunodeficiencies (including but not limited to Severe Combined Immunodeficiency Syndrome, Wiskott-Aldrick syndrome, CD40 ligand deficiency, T-cell deficiencies) * Acute leukemias: * Subjects must be ineligible for conventional myeloablative transplantation; * Resistant or recurrent disease after at least one standard combination chemotherapy regime or first remission patients at high risk of relapse OR First remission patients at high risk of relapse: * Acute myeloid leukemia (AML)- antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular features (e.g. Flt3-ITD mutation, mixed-lineage leukemia [MLL], wildtype NPM1); * Acute lymphocytic leukemia (ALL)- high or standard risk ALL * Chronic Myeloid Leukemia (CML): * Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine kinase inhibitors), second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation * Myeloproliferative and myelodysplastic syndromes (MDS): * Myelofibrosis (with/without splenectomy) with intermediate to high risk features * Advanced polycythemia vera not responding to standard therapy * MDS with an international prostate symptom score (IPSS) score of Int-2 or higher * MDS with lower IPSS scores Int-1 or less with severe clinical features such as severe neutropenia or thrombocytopenia or high risk chromosome abnormalities such as monosomy 7 * Secondary massively parallel signature sequencing (MPSS) with any IPSS scores * Chronic myelomoncytic leukemia * Lymphoproliferative disease: * Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or persistent) fludarabine refractory or with less than 6 months duration of complete response (CR) between courses of conventional therapy * Multiple myeloma, progressive disease after autologous stem cell transplant or as planned tandem (allogeneic transplant after prior autologous stem cell transplant) * Waldenstroms macroglobulinemia (failed one standard regimen) * High grade NHL and diffuse large B-cell lymphoma (DLBCL) * Not eligible for conventional myeloablative HSCT OR failed autologous HSCT * First remission lymphoblastic lymphoma, or small, non-cleaved cell lymphoma or mantle cell lymphoma * Hodgkin disease: * Relapsed or refractory after front-line therapy * Failed or were not eligible for autologous transplantation * Failed prior autotransplant * Age >= 3 and =< 75 years for blood and bone marrow transplants and age >= 3, < 60 for cord blood transplants * No serious uncontrolled psychiatric illness * No concomitant active malignancy other than non-melanoma skin cancer * Non-pregnant and non-nursing women (women or men with reproductive potential should agree to use an effective means of birth control) * Patients may have received prior autologous bone marrow transplant (BMT) or prior myeloablative allogeneic BMT (at least 60 days have elapsed) * At least 2 weeks since prior chemotherapy, radiation treatment and/or surgery * Informed consent * DONOR: Permissible HLA matching: Related donors- single antigen mismatch at HLA A, B or DRB 1; unrelated donors- a single antigen mismatch at HLA A, B, or C, +/- additional single allele level mismatch at A, B, C or DRB1; cord blood >= 4 out of 6 antigen match at HLA A, B, DRB1) * DONOR: Compatibility at the four most informative HLA loci: A, B, C and DRB1 are important for reducing the risk of GVHD and successful transplant outcomes; the A, B, C and DRB1 loci comprise 8 possible alleles (a haplotype being inherited from each parent); one additional locus, HLA-DQ, is also typed to ascertain haplotypes and assist in the search for a compatible donor; however mismatching at DQ has not been shown to be associated with adverse outcomes; high resolution molecular typing (at the allele level) is now the standard of care for unrelated donor searches and allows greater refinement of the search strategy * DONOR: Matched related donor: a single antigen mismatch at A, B, or the DR transplant from a family member is associated with a higher risk of GVHD but similar overall survival when compared to full identity at these 3 regions; related donor/recipient pairs must be matched at 5 of 6 HLA antigens (A, B, DRBl) * DONOR: Unrelated donor: when evaluating patients for unrelated donor transplant, a higher degree of matching is preferred due to minimize the risk of GVHD; the A, B, C, DRB1 and DQ loci, comprising 10 possible alleles, will be typed routinely for all unrelated transplants; given the higher risk of TRM in mismatched transplants, RIT is often the best way to mitigate the risk; evolving data from the National Marrow Donor Program now makes it possible to estimate the risks of donor-recipient HLA mismatch at the allele or antigen level; the higher risk from HLA-mismatching must be carefully assessed with respect to the clinical urgency and the patient's risk by the transplant physician; antigen level mismatches at DQ are inconsequential to transplant outcomes and are ignored with respect to donor selection for the purposes of this protocol, with matching requirements confined to the 8 loci involving HLA A, B, C and DRB1; for the purpose of this protocol, a single antigen mismatch at HLA A, B, or C, with or without additional single allele level mismatch may participate in this protocol for voluntary unrelated donors (blood or marrow); patients must be at least antigen-level matched at DRB1 * DONOR: If a patient has no suitable family donor matched for 5 of 6 HLA antigens (A, B, DRB1) and no suitable unrelated donor is identified or for reasons of urgency, the patient can be considered a candidate for cord blood transplant, provided a cord blood donor is identified with a >= 4 out of 6 antigen match at HLA A, B, DRB1 antigens; the cord blood product must provide a minimum of 2 x 10^7 nucleated cells/kg, test negative for HIV and Hepatitis A, Band C, and sterility assays have no growth; the cord blood products are located through the National Marrow Donor Program, the American Registry, or the Bone Marrow Donor Worldwide or other established registries, and may be stored in the N.Y Placental Cord Blood Bank, the St. Louis Cord Blood Bank, or any of the established, registered International blood and marrow banks * DONOR: Donor must be healthy and have nonreactive test results for all infectious disease assays as required by state and federal regulations; donors who screen seropositive for hepatitis and/or syphilis must be cleared by infectious disease consultation * DONOR: The donor must have no uncontrolled cardiopulmonary, renal, endocrine, hepatic or psychiatric disease to render donation unsafe * DONOR: The donor must be able to give informed consent for peripheral blood stem cell collection or bone marrow collection * DONOR: Syngeneic donors are not eligible * DONOR: Donors who have poor peripheral venous access, may require central venous line placement for stem cell apheresis Exclusion Criteria: * Uncontrolled central nervous system (CNS) disease (for hematologic malignancies) * Karnofsky (adult) or Lansky (for =< 16 years) performance status =< 50% * Diffusing capacity of the lung for carbon monoxide (DLCO) less than 40% predicted, corrected for hemoglobin (Hb) and/or alveolar ventilation * Cardiac: left ventricular ejection fraction less than 40% * Bilirubin >= 3 x upper limit of normal * Liver alkaline phosphatase >= 3 x upper limit of normal * Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) >= 3 x upper limit of normal * Child's class B and C liver failure * Calculated creatinine clearance < 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics * Patients who have received maximally allowed doses (given in 2 Gy fractions, or equivalent) of previous radiation therapy to various organs as follows: * Mediastinum 40 Gy * Heart (any volume) 36 Gy * Whole lungs 12 Gy * Small bowel (any volume) 46 Gy * Kidneys 12 Gy * Whole liver 20 Gy * Spinal cord (any volume) 36 Gy * Whole brain 30 Gy Enrollment of patients who previously receive higher than allowed dose of radiation to a small volume of lungs, liver, and brain will be determine by the discretion of the radiation oncologist on the study * Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient * Human immunodeficiency virus (HIV) positive * Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening * Females of childbearing potential with a positive pregnancy test

Study Objectives Pembrolizumab is approved for advanced stage non-small cell lung cancer. However, the response rate is low (around 10-15 %) in patients treated in Macau SAR, China. The investigators hypothesize CD38 expressing cells and/or other immune populations will help to predict response. Conditions: NSCLC Stage IV Intervention / Treatment: DRUG: Pembrolizumab Location: China Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Above 18 years of age * Locally advanced (stage IIIB) or metastatic (stage IV) NSCLC, not amenable to curative surgery or radiotherapy * With PD-L1test available * Progressed on previous treatment, or treatment native patients. Patients may have also received additional lines of treatment * Received pembrolizumab treatment in the participating site. Exclusion Criteria: * Enrollment in studies that prohibit any participation in this observational study * No serum samples available

Study Objectives We will study the efficacy of FDA approved intravenous (IV) acetaminophen ("Ofirmev", © 2011 Cadence Pharmaceuticals, Inc.) in reducing opioid consumption after minimally invasive thoracic surgery in a double blind randomized trial. This drug has been shown in Europe to reduce the need for patient controlled analgesia and the total dose of opioids, which have serious side effects in thoracic surgery patients. We will compare the use of IV patient-controlled morphine (PCA) in two groups of subjects in treating postoperative pain. We will determine if IV acetaminophen reduces post-operative morphine requirements (primary end point). We will also assess subject pain scores and post-operative complications associated with pain management as secondary end points. Our hypothesis is that the study arm receiving intravenous acetaminophen will have lower total morphine consumptions compared to the placebo group. Conditions: Lung Tumor Intervention / Treatment: DRUG: IV Acetaminophen, DRUG: Saline Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Any elective VATS patients with low probability of conversion to thoracotomy as determined by surgery. * Ages 18-99 * American Society of Anesthesiologists Physical Status I-III, hemodynamically stable * Male or female Exclusion Criteria: * Age less than 18. * Patient refusal * High probability of conversion to thoracotomy as determined by surgeon * Conversion of procedure to thoracotomy (subjects will be withdrawn if VATS procedure is converted to thoracotomy, as thoracotomy is more invasive and will likely require additional analgesia such as neuraxial and regional anesthesia). * Scheduled procedure of VATS Pleurodesis/decortication * History of Interstitial Lung Disease * Emergency case * Known allergy/adverse reaction to acetaminophen, morphine, or fentanyl * History of drug or alcohol abuse * Patients on preoperative analgesic therapy within one week of surgery * Contraindication to self administered morphine (unable to understand PCA) * Need for postoperative mechanical ventilation * Necessary major deviation for intraoperative study protocol as per the discretion of the intraoperative attending anesthesiologist * History of congestive heart failure, renal failure, liver failure * Pregnant or breastfeeding women * Weight less than 51 kg

Study Objectives This phase I/II trial studies the side effects and best dose of nivolumab when given with or without ipilimumab to see how well they work in treating younger patients with solid tumors or sarcomas that have come back (recurrent) or do not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas. Conditions: Metastatic Melanoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hodgkin Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Melanoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Rhabdomyosarcoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hodgkin Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Melanoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Rhabdomyosarcoma, Stage III Cutaneous Melanoma AJCC v7, Stage IIIA Cutaneous Melanoma AJCC v7, Stage IIIB Cutaneous Melanoma AJCC v7, Stage IIIC Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7, Unresectable Melanoma Intervention / Treatment: BIOLOGICAL: Ipilimumab, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Nivolumab, OTHER: Pharmacological Study Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Parts A & C: patients must be >= 12 months and < 18 years of age at the time of study enrollment * Parts B1-B6, B8, D1-D6, E3, E4: patients must be >= 12 months and =< 30 years of age at the time of study enrollment * Part B7: patients must be >= 12 months and < 18 years of age at the time of study enrollment * Patients must have had histologic verification of malignancy at original diagnosis or relapse * Parts A & C: patients with recurrent or refractory solid tumors, without central nervous system (CNS) tumors or known CNS metastases, are eligible; note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated * Part B1: patients with relapsed or refractory neuroblastoma * Part B2: patients with relapsed or refractory osteosarcoma * Part B3: patients with relapsed or refractory rhabdomyosarcoma * Part B4: patients with relapsed or refractory Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) * Part B5: patients with relapsed or refractory Hodgkin lymphoma * Part B6: patients with relapsed or refractory non-Hodgkin lymphoma * Part B7: patients with unresectable melanoma or metastatic melanoma or relapsed melanoma or refractory melanoma * Part B8: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without Response Evaluation Criteria in Solid Tumors [RECIST] measurable lesion) * Once the dose-escalation portion of Part A is completed, cohorts that are open concurrently for eligible patients (including Parts B and C and potential pharmacokinetic [PK] expansion cohorts) may be selected at the treating physician's discretion pending slot availability; in the event a disease group cohort in Part B is completed after the initial stage of Simon's optimal two-stage design, for selected disease cohorts, a corresponding cohort in the same disease group for select disease types will be open in Part D: * Part D1: Patients with relapsed or refractory neuroblastoma * Part D2: Patients with relapsed or refractory osteosarcoma * Part D3: Patients with relapsed or refractory rhabdomyosarcoma * Part D4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET * Part D5: Patients with relapsed or refractory non-Hodgkin lymphoma * Part D6: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without RECIST measurable lesion) * Part E3: Patients with relapsed or refractory rhabdomyosarcoma * Part E4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET * Parts A & C: patients must have either measurable or evaluable disease * Parts B, D & E: patients must have measurable disease for Parts B1-B6, D1-D5, E3 and E4; melanoma patients in Part B7 must have either measurable or evaluable disease; neuroblastoma patients in Parts B8 and D6 must be evaluable for MIBG response without evidence of RECIST measurable lesions * Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life * Karnofsky >= 50% for patients > 16 years of age and Lansky >= 60 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive * At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea) * Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair * Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): At least 7 days after the last dose of agent * Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1 * External beam radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after total body irradiation (TBI), craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation. * Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days must have elapsed since systemically administered radiopharmaceutical therapy * Cellular therapy: >= 42 days must have elapsed since the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.) * Patients must not have received prior exposure to nivolumab; for patients enrolled in Parts C, D, and E patients must not have received prior nivolumab or ipilimumab * For patients with solid tumors without known bone marrow involvement: * Peripheral absolute neutrophil count (ANC) >= 750/mm^3 * Platelet count >= 75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients with a solid tumor must be evaluable for hematologic toxicity, for Parts A and C; if dose-limiting hematologic toxicity is observed on either Part A or C, all subsequent patients enrolled must be evaluable for hematologic toxicity on that Part * Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows: * Age 1 to < 2 years: maximum serum creatinine (mg/dL) 0.6 for males and females * Age 2 to < 6 years: 0.8 for males and females * Age 6 to < 10 years: 1 for males and females * Age 10 to < 13 years: 1.2 for males and females * Age 13 to < 16 years: 1.5 for males and 1.4 for females * Age >= 16 years: 1.7 for males and 1.4 for females * Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L * No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air * Serum lipase =< ULN at baseline; patients with glucose intolerance should be on a stable regimen and be monitored * All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines * Tissue blocks or slides must be sent for all patients; if tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment Exclusion Criteria: * Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as there is yet no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab * Patients requiring daily systemic corticosteroids are not eligible; patients must not have received systemic corticosteroids within 7 days prior to enrollment; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid; Note: use of topical or inhaled corticosteroids will not render a patient ineligible * Patients who are currently receiving another investigational drug are not eligible * Patients who are currently receiving other anti-cancer agents are not eligible * Patients with CNS tumors or known CNS metastases will be excluded from this trial; patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows not evidence for active disease; patients with extra axial disease (e.g. skull [bone] metastasis that do not invade the dura) may enroll if there is no evidence for CNS edema associated with the lesion * Patients with a history of any grade autoimmune disorder are not eligible; asymptomatic laboratory abnormalities (e.g. antinuclear antibody [ANA], rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder * Patients with >= grade 2 hypothyroidism due to history of autoimmunity are not eligible; note: hypothyroidism due to previous irradiation on thyroidectomy will not impact eligibility * Patients who have an uncontrolled infection are not eligible * Patients with a history of congestive heart failure (CHF) or are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must have adequate cardiac function as clinically indicated: * Corrected QT interval (QTC) =< 480 msec * Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by gated radionuclide study * Patients with known human immunodeficiency virus (HIV) or hepatitis B or C are excluded * Patients who have received prior solid organ transplantation are not eligible * Patient who have received allotransplantation are not eligible * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible * Patients who have received prior anti-PD1 directed therapy (monoclonal antibody [mAb] or small molecule) are not eligible * Parts C, D, and E: patients who have received prior ipilimumab are not eligible

Study Objectives The aim of this study is to evaluate if the multi modality treatment pemetrexed combined with cisplatin and radiotherapy can lead to a better tumor control and/or a better side-effect profile in patients with locally advanced NSCLC. Patients will be randomized between 3 cycles of induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy followed by 3 cycles of adjuvant combination chemotherapy. Conditions: Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: combination chemotherapy (pemetrexed + cisplatin), RADIATION: thoracic irradiation + pemetrexed Location: Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * cytological or histological proven NSCLC * unresectable stage III NSCLC * presence of at least one measurable lesion (RECIST criteria) * adequate haematological, renal and hepatic function * adequate lung function reserve * good condition, weight loss <10 % over previous 6 months, life expectancy > 3 months Exclusion Criteria: * previous chemo- or radiotherapy for NSCLC * distant metastasis or a malignant pleural or pericardial effusion * second active primary malignancy or serious concomitant medical disease * interstitial lung disease * auto-immune systemic disease with potential involvement of the lungs * inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period * concomitant use of amiodarone

Study Objectives the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin in patients with cMET-dysregulated advanced solid tumors Conditions: cMET-dysregulated Advanced Solid Tumors Intervention / Treatment: DRUG: INC280, DRUG: digoxin, DRUG: rosuvastatin Location: Italy, Spain, United Kingdom, United States, Greece, Belgium, Austria, Czechia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Patients must have: * advanced solid tumors and have confirmed cMET dysregulation * at least one measurable lesion as defined by RECIST 1.1. * recovered from all toxicities related to prior anti-cancer therapies * adequate organ function * ECOG performance status (PS) of 0 or 1 Exclusion Criteria: Patients must not have: * known hypersensitivity to any of the excipients of INC280 * prior treatment with cMET or HGF-targeting inhibitor * known hypersensitivity to digoxin or rosuvastatin or its excipients * symptomatic central nervous system (CNS) metastases who are neurologically unstable * presence or history of carcinomatous meningitis * history of another primary malignancy that is currently clinically significant or currently requires active intervention * Clinically significant, uncontrolled heart diseases, including QTcF >= 450 msec (male patients), >= 460 msec (female patients) on the screening ECG * Thoracic radiotherapy to lung fields <= 4 weeks prior to starting INC280 * Major surgery within 4 weeks prior to starting INC280 * Patients receiving unstable or increasing doses of corticosteroids. * Impairment of GI function or GI disease that may significantly alter the absorption of INC280 * Patients who have received, or are expected to receive digoxin or rosuvastatin within 21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the DDI phase. Other protocol-defined inclusion/exclusion criteria may apply

Study Objectives This study aims to characterize the profile and outcomes for patients with Squamous Cell Carcinoma of the Lung (SqCC) who progress on 1L pembrolizumab in combination with platinum based chemotherapy and receive afatinib as second line (2L) therapy. Conditions: Squamous Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Second line (2L) afatinib, DRUG: Second line chemotherapy Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Diagnosis of squamous or mixed histology non-small cell lung cancer * Treated with pembrolizumab in combination with platinum-based chemotherapy as initial therapy for advanced or metastatic disease (stage IIIB or IV) * First cycle of pembrolizumab received after 06/01/2018 * Permanently discontinued 1L pembrolizumab treatment * Initiated second-line treatment at least 3 months prior to the date of data collection, with either : * Afatinib * Any chemotherapy * Age >= 18 years Exclusion Criteria: *Received pembrolizumab in combination with platinum-based chemotherapy as part of an interventional clinical trial

Study Objectives The goal of this trial is to assess the safety, therapeutic dose, and leukostimulatory activity of the preparation Panagen in the therapeutic schemes for treating cancer diseases in the patients receiving a standard chemotherapy for breast cancer of stages II-IV (with distant metastases). Conditions: Breast Cancer Intervention / Treatment: DRUG: Panagen, DRUG: Placebo, PROCEDURE: Chemotherapy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Signed and dated written informed consent * Women at an age of >=18 years * Stage II-IV breast cancer (with distant metastases) * The patients will be subject to chemotherapy with cyclophosphan/doxorubicin/ fluorouracil as a standard chemotherapy for treating breast cancer * The patients have not been earlier subject to chemotherapy * Functional status according to the Eastern Cooperative Oncology Group (ECOG) <=2 * Leukocyte counts of >=3 × 109/L before the treatment course * Neutrophil counts of >=1.5 × 109/L before the treatment course * Platelet counts of >=100 × 109/L before the treatment course * Adequate heart function * Adequate liver function, that is, alanine aminotransferase / aspartate aminotransferase (ALT / AST) activity < 2.5 × upper limit of normal (ULN); acid phosphatase activity < 5 × ULN; and bilirubin concentration < 5 × ULN; and * Adequate renal function, that is, the creatinine concentration in the blood serum < 1.5 × ULN; urea concentration < ULN; and endogenous creatinine clearance Exclusion Criteria: * Participation in clinical trials less than 30 days before sequential randomization * Previous exposure to Panagen or any other leukostimulatory drugs at a stage of clinical development * Known hypersensitivity to cyclophosphan, doxorubicin, or fluorouracil * Therapy with systemically active antibiotics less than 72 h before the beginning of chemotherapy * Long-term oral intake of corticosteroids * Previous X-ray therapy performed less than 4 weeks before randomization * Previous transplantation of hematopoietic stem cells * Other malignant neoplasms during the last 5 years except for basal cell or flat cell carcinoma or intraepithelial carcinoma of the uterine cervix * Any disease or state that according to the opinion of researcher can influence patient's safety or the estimation of a final trial point; and * Pregnant and nursing women; the fertile patients should use chemical or barrier contraceptives during the period of trials

Study Objectives Lung cancer accounts for 30% of all cancers among American war Veterans and remains the leading cause of cancer related deaths. Half of all lung cancers are metastatic non-small cell lung cancer (NSCLC), with a 2-year survival rate of 10%. Immunotherapy with immune checkpoint inhibitors (ICI) has emerged as a promising therapeutic strategy that aims to harness the immune system to fight lung cancer. However, given the modest response rates of 20-25% to these immune checkpoint inhibitors, there is a greater desire to extend their benefits to more patients. Along with the desire to extend their benefits, there is a critical need for the development of novel approaches that can expand the benefit from immune checkpoint inhibitors and create more durable responses, prolonging survival from lung cancer. The investigators' studies show that extended dexamethasone (Dex) treatment induces irreversible cell cycle blockade and a senescence phenotype through chronic activation of the p27Kip1 gene in glucocorticoid receptor (GR) overexpressing lung adenocarcinoma (AC) cell populations. Further, following withdrawal of Dexamethasone, proteins associated with the senescence associated secretory phenotype (SASP) strongly attracted and expanded T-cells, NK cells and monocytes stimulated tumor cell cytolytic activity of NK cells. Therefore, dexamethasone may induce a persistent senescence phenotype in tumor cell sub-populations expressing moderate/high levels of GR and resultant chemokines produced by the senescent cells will mobilize host immune cells to reboot response to immune checkpoint inhibitors following complete Dexamethasone withdrawal. Conditions: Non-Small Cell Lung Cancer, Immunotherapy Intervention / Treatment: DRUG: Dexamthasone 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: * 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 a life expectancy of at least 6 months. * Have a histologically confirmed diagnosis of stage IV NSCLC (includes patients who have progressed on durvalumab for Stage III NSCLC) and have at least one measurable lesion based on RECIST v1.1. * Have a performance status of 0, 1 or 2 on the ECOG Performance Scale (Appendix 15.1). * Demonstrate adequate organ function all screening labs should be performed within 14 days of enrollment. * Female subject of childbearing potential should have a serum pregnancy within 14 days of enrollment and 72 hours prior to receiving the first dose of study medications. * Female subjects of childbearing potential must be willing to use a highly effective method of contraception as outlined in Section 6.3.3 for the course of the study through 180 days after the last dose of study medications. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Adequate tissue sample for correlative studies. A new sample is not necessary if archival specimen is available and has adequate amount of tumor content (at least 30%). This needs to be determined by a pathologist. Exclusion Criteria: * Received palliative radiation within 7 days of enrollment. * Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. * Note: the time requirement for no evidence of disease for 5 years does not apply to the NSCLC tumor for which a subject is enrolled in the study. The time requirement also does not apply to subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. * 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 enrollment 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 enrollment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has active autoimmune disease that has required systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * Note: 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. * Subjects requiring daily corticosteroids >10mg of prednisone (or its equivalent) would be excluded from the study. * Note: Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would NOT be excluded from the study. * Has evidence of interstitial lung disease or a history of non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management. * Note: Lymphangitic spread of the NSCLC is not exclusionary. * Has an active infection requiring systemic therapy. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Subjects with cognitive functioning/impairment based on medical record review ad physician decision. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment. * Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment. * Has a known history of active TB (Bacillus Tuberculosis). * Has known active Hepatitis B or Hepatitis C. * Has received a live vaccine within 30 days of enrollment. * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed. * BASELINE CORTICOSTEROID AT STUDY ENTRY - subjects may not be on any steroids (dexamethasone, prednisone, etc) at the time of consent/study start.

Study Objectives This is a Phase 3 randomized, double blind, placebo controlled study of tasquinimod in asymptomatic to mildly symptomatic patients with metastatic CRPC to confirm the effect of tasquinimod on delaying disease progression compared with placebo. Approximately 1200 eligible patients with metastatic CRPC will be randomly assigned in a 2:1 ratio to 1 of 2 treatment groups: Treatment Group A (tasquinimod 0.25, 0.5, or 1 mg/day; n=800) or Treatment Group B (placebo; n=400). Conditions: Prostate Cancer Intervention / Treatment: DRUG: tasquinimod, DRUG: Placebo Location: Canada, Turkey, Lithuania, United States, Greece, Colombia, Taiwan, France, Poland, Israel, India, Italy, Netherlands, Peru, Ukraine, United Kingdom, Russian Federation, Bulgaria, Estonia, Spain, Brazil, Lebanon, Belgium, China, Latvia, Sweden, Mexico, Chile, Germany, Czech Republic, Korea, Republic of, New Zealand, Romania, Australia, Slovakia, Argentina, Panama Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Age at least 18 years at the time of signing the informed consent form. For patients in Taiwan the minimum age is 20 years. * Histologically confirmed diagnosis of adenocarcinoma of the prostate. * Evidence of bone metastatic disease on radiographic examination, whether from bone scan or other imaging modality. * Castrate levels of serum testosterone (<=50 ng/dL or 1.7 nmol/L). * Evidence of progressive disease. * Karnofsky score >=70%. * Meet screening laboratory values as specified in thr protocol. * If sexually active with partner of childbearing potential, patient will agree to use adequate contraceptive methods (barrier contraceptive with spermicide or vasectomy) while on study drug. The adequate contraceptive method should be continued for 14 days after the patient stops taking study drug. * No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin). * Able to swallow and retain oral medication. * Able to adhere to the study visit schedule and other protocol requirements. * Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the investigator and to comply with the requirements of the entire study. * Able (or patient's legal guardian, if applicable) to sign and date the written informed consent after being informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information. Exclusion Criteria: * Prior cytotoxic chemotherapy for the treatment of prostate ca within 2 years or within 4 weeks for Estracyt (estramustine) prior to study treatment. * Previous anticancer therapy using radiation, biologics or vaccines, including abiraterone, TAK-700 (Orteronel), or MDV3100 within 4 weeks prior or sipuleucel-T (Provenge) within 2 weeks prior to the start of study treatment. If radiation therapy is applied after baseline scan, a new baseline scan needs to be done at least 4 weeks after the radiation therapy. * Previous therapy with antiandrogens within 4 weeks (within 6 weeks for bicalutamide eg, Casodex®) prior to study treatment. * Concurrent use of other anticancer agents or treatments, with the following exceptions: * Ongoing treatment with luteinizing hormone-releasing hormone agonists or antagonists, denosumab (Prolia) or bisphosphonate (eg, zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed. * Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment. * Prostate ca pain that requires ongoing treatment with narcotic analgesics or warrants the initiation of radio- or chemotherapy. * Ongoing treatment with warfarin unless the international normalized ratio (INR) is well controlled and below 4 (Section 4.6.8.1). * Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days. * Systemic exposure to ketoconazole or other strong cytochrome P450 (CYP) 3A4 isozyme inhibitors or inducers within 14 days prior to the start of study treatment. Systemic exposure to amiodarone is not allowed within 1 year prior to the start of study treatment. * Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment. * Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment. * Simultaneous participation in any other study involving treatment with investigational drugs or having received treatment with investigational drugs less than 4 weeks prior to the start of study treatment. * Myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, class III/IV congestive heart failure, cerebrovascular accident, transient ischemic attack, or limb claudication at rest, within 6 months prior to start of study treatment and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and uncontrolled atrial or ventricular arrhythmias. * History of pancreatitis. * Known brain or epidural metastases. * Known positive serology for HIV (patients with known history of HIV will be excluded because of potential for unforeseen toxicity and morbidity in an immunocompromised host). * Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of a chronic viral hepatitis or known viral hepatitis carrier (patients who have recovered from hepatitis will be allowed to enter the study). * Patients with active tuberculosis (TB), or with known, untreated latent TB. (Country-specific TB therapy should have been given for at least 30 days prior to the start of study treatment and the patient should intend to complete the entire course of that therapy.) * Any condition, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could confound the ability to interpret data from the study or places the patient at unacceptable risk if he participates in the study. * Any patient who in the opinion of the investigator should not participate

Study Objectives This is a global Phase III, two-arm, open-label, multicenter, randomized study to investigate the pharmacokinetics, efficacy, and safety of the fixed-dose combination (FDC) of pertuzumab and trastuzumab for subcutaneous (SC) administration in combination with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in the neoadjuvant/adjuvant setting. Conditions: Early Breast Cancer Intervention / Treatment: DRUG: Cyclophosphamide, DRUG: Doxorubicin, DRUG: Docetaxel, DRUG: Paclitaxel, DRUG: Pertuzumab IV, DRUG: FDC of Pertuzumab and Trastuzumab SC, DRUG: Trastuzumab IV, DRUG: Trastuzumab SC, PROCEDURE: Surgery, RADIATION: Post-operative Radiotherapy, DRUG: Hormone Therapy Location: Canada, United States, Taiwan, Czechia, France, Poland, Thailand, Italy, Ukraine, United Kingdom, Russian Federation, Spain, Brazil, Belgium, Mexico, Germany, Japan, Korea, Republic of, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Ability to comply with the study protocol, in the investigator's judgment * Eastern Cooperative Oncology Group (ECOG) Performance Status <=1 * Female and male patients with Stage II - IIIC (T2-T4 plus any N, or any T plus N1-N3, M0), locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer * Primary tumor >2 cm in diameter, or node-positive disease (clinically or on imaging, and node positivity confirmed with cytology and/or histopathology) * HER2-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material. * Hormone receptor status of the primary tumor, centrally confirmed * Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy * Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for central confirmation of HER2 and hormone receptor status and additional biomarker research * Baseline left ventricular ejection fraction (LVEF) >=55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) * For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent or use one highly effective non-hormonal contraceptive method with a failure rate of <1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period * For men: men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of HER2-targeted therapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period. * A negative serum pregnancy test must be available prior to randomization for WOCBP, unless they have undergone surgical sterilization * No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment Exclusion Criteria: * Stage IV (metastatic) breast cancer * Patients with a history of invasive breast cancer * Patients with a history of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin * Patients who have received any previous systemic therapy for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer * Patients who have a past history of ductal carcinoma in situ or lobular carcinoma in situ if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast * Patients with high-risk for breast cancer who have received chemo-preventative drugs in the past are not allowed to enter the study * Patients with multicentric breast cancer, unless all tumors are HER2-positive * Patients with bilateral breast cancer * Patients who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes * Axillary lymph node dissection prior to initiation of neoadjuvant therapy * Sentinel lymph node biopsy prior to neoadjuvant therapy * Treatment with any investigational drug within 28 days prior to randomization * Serious cardiac illness or medical conditions * Inadequate bone marrow function, renal function or impaired liver function * Current severe, uncontrolled systemic disease that may interfere with planned treatment * Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study * Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis * Concurrent, serious, uncontrolled infections, or known infection with HIV * Known hypersensitivity to study drugs, excipients, and/or murine proteins * Current chronic daily treatment with corticosteroids * History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, colon, skin, and/or non-melanoma skin carcinoma * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome

Study Objectives To determine the response rate, complete and partial, of patients with indolent lymphoma receiving Rituxan and BEAM with autologous stem cell transplant. Conditions: Lymphoma Intervention / Treatment: DRUG: Rituxan, DRUG: BEAM, PROCEDURE: Autologous stem cell transplant 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: * Any low-grade B-cell, CD20 positive, non-Hodgkin's lymphoma that is felt to otherwise be a transplant candidate (relapsed, induction failure, first PR or CR). o Small lymphocytic, marginal zone, mantle cell, and follicular histologies. * At least 19 years of age * Signed written informed consent * Expected survival of at least 6 months * WHO performance status greater or equal to 2 * Male or female subjects of reproductive potential who are able to follow accepted birth control measures. Exclusion Criteria: * No history of T-cell lymphoma * Not pregnant or lactating women * No serious disease or condition that, in the opinion of the investigator, would compromise the subject's ability to participate in the study

Study Objectives Open-label, multicenter, dose-escalation, safety, pharmacodynamic, and pharmacokinetic study. Conditions: Solid Tumor Intervention / Treatment: DRUG: PEGPH20 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Pathologic (histologic or cytologic) confirmation of metastatic or locally advanced solid tumor. * Patients who have experienced disease progression after receiving appropriate standard / approved chemotherapy and for whom no further standard or palliative treatment measures exist, or who have chosen to decline standard or palliative treatment. * One or more tumors measurable by RECIST criteria. * Karnofsky performance status >= 70%. * Recovery from any toxic or other effects of all previous therapy, including radiation, chemotherapy and surgery. * Negative serum or urine pregnancy test result in women of childbearing potential. * For men and women of child-producing potential, agreement to use effective contraception (hormonal or barrier birth control or abstinence) from the time of screening before study entry and throughout study participation. Exclusion Criteria: * Brain metastasis. * New York Heart Association Class III or IV cardiac disease, myocardial infarction, or cardiac arrhythmia requiring medical therapy. * Known allergy to hyaluronidase. * Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions including psychiatric illness) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor. * Women currently breast feeding. * Concurrent participation in any other interventional therapeutic study.

Study Objectives This phase II trial studies how well domatinostat (4SC-202) works in combination with avelumab in adult patients with advanced unresectable and/or metastatic Merkel Cell Carcinoma that have progressed on a previous therapy with an anti-PD-(L)1 antibody Conditions: Merkel Cell Carcinoma Intervention / Treatment: DRUG: domatinostat in combination with avelumab Location: Germany, Netherlands, Italy, Spain, Belgium, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed Merkel Cell Carcinoma (MCC) * ECOG performance status <= 1 * MCC in an advanced, unresectable stage III or metastatic stage IV (includes patients who refused surgical resection or are not eligible for such surgical resection) * Progressing on previous anti-PD-(L)1 antibody monotherapy within the last 12 weeks before planned first administration of study medication Exclusion Criteria: * History of serious anti-PD-(L)1 therapy-related adverse reactions prohibiting further avelumab treatment * More than one line of previous systemic anti-neoplastic therapy other than anti-PD-(L)1 antibody monotherapy * Palliative radiation therapy of single lesions within 2 weeks before planned administration of study medication * Presence of significant active or chronic disease (infections, immunodeficiencies, cardiovascular, psychiatric disorders)

Study Objectives The aim of this study is to determine whether selenium supplementation leads to changes in selenium levels and gene expression profiles in prostate tissue. Conditions: Prostatic Neoplasms, Prostate Cancer Intervention / Treatment: DIETARY_SUPPLEMENT: Selenium Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * male * biopsy proven prostate cancer * scheduled for radical prostatectomy Exclusion Criteria: * liver diseases (e.g. hepatitis) * kidney diseases * inflammatory bowel diseases * use of dietary supplements containing selenium * adjuvant therapy for prostate cancer (e.g. hormonal therapy, HIFU) * previously or concurrent diagnosed with cancer, other than prostate cancer

Study Objectives This study will compare two strategies for bowel cleansing prior to inpatient colonoscopy: the entire preparation taken the night before the procedure versus half the preparation taken the night before the procedure, and the other half taken the morning of the procedure. Conditions: Gastrointestinal Hemorrhage, Colon Cancer, Diverticulosis Intervention / Treatment: DRUG: Go-Lytely, DRUG: Go Lytely Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: DIAGNOSTIC Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * any diagnosis for which colonoscopy is indicated Exclusion Criteria: * ileus * severe colitis/toxic megacolon * gastric retention * bowel perforation * gastrointestinal obstruction * gastroparesis that precludes oral bowel preparation * pregnant or lactating women * allergy to polyethylene glycol. * unable to give consent

Study Objectives This study is a first-in-human (FIH) study which is required to understand the PK characteristics, MTD, and safety profile of NOV1601(CHC2014) in subjects with solid organ malignancies. Conditions: Phase 1, Solid Tumor, Adult Intervention / Treatment: DRUG: NOV1601(CHC2014) Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria(partial): * Pathological confirmation of malignancy and evidence of metastatic or surgically unresectable disease * At least one evaluable or measurable lesion should be present and identified according to Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1 or Response Assessment in Neuro-Oncology(RANO) * Relapse after or refractory to systemic drug therapy to malignancy, at least one regimen of cytotoxic chemotherapy, kinase inhibitors including tyrosine kinase inhibitors or immunotherapy which is considered as standard of care if there is no standard regimen recommended, then no experience of systemic drug therapy is acceptable * Patients with primary central nervous system(CNS) tumors or metastasis, if they have been neurologically stable * Symptoms should be under control by stable dose of glucocorticoids and analgesic drugs for symptom control at least 2 weeks prior to starting the treatment * Stable dose of glucocorticoids and analgesic drugs for symptom control should be maintained throughout the study * Subjects should be off from radiotherapy for at least 14 days prior to the start of study treatment(C1D1) without symptom aggravation Exclusion Criteria(partial): * Prior high-dose chemotherapy requiring hematopoietic stem cell transplantation * History or evidence of suspicious leptomeningeal disease * Previous surgery of gastrectomy, gastrostomy or any medical condition which interferes with oral ingestion of capsule * Indwelling percutaneous drainage of bile and chest tube * Evidence of or suspicious symptomatic spinal cord compression, unless appropriately treated and neurologically stable off glucocorticoid for at least 2 weeks

Study Objectives This is a Phase 1b, open-label, dose escalation study to evaluate the safety, tolerability, PK, and immunogenicity of an ADG116-pembrolizumab combination regimen in patients with advanced/metastatic solid tumors. Study drug ADG116, is an anti -CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4. Pembrolizumab is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody) which is indicated for the treatment of patients across a number of indications. The treatment strategy of using anti-PD 1 therapy combined with anti-CTLA-4 therapy is to explore the potential of combination checkpoint inhibition regimens for the enhanced antitumor efficacy results. Conditions: Advanced/Metastatic Solid Tumors Intervention / Treatment: DRUG: ADG116 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Patients must meet all of the following inclusion criteria to be eligible for participation in this study: 1. >= 18 years of age at the time of informed consent. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration over the previous 2 weeks. 3. Patients with advanced or metastatic solid tumors, histologically or pathologically confirmed, who have progressed after all standard therapies, or for whom no further standard therapy exists. Patients who have declined standard therapy or have no access to standard therapy may be enrolled and the reasons for lack of access need to be documented. 4. Patients should have at least 1 measurable lesion at baseline according to the definition of RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 5. Patients previously treated with anti-CTLA 4 checkpoint inhibitors or anti programmed cell death 1 (PD-1)/L1 will also be recruited if they meet all eligibility criteria. For anti-PD-1/L1 patients, patients must have progressed on treatment with an anti PD 1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. Anti PD-1/L1 treatment progression is defined by meeting all of the following criteria: 1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb. 2. Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression. 3. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. i. Progressive disease is determined according to iRECIST. ii. This determination is made by the Investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression. 6. Adequate hematologic function, defined by the following: 1. Absolute neutrophil count (ANC) >= 1.5 × 109/L, without the use of granulocyte colony stimulating factor such as filgrastim within 2 weeks prior to study treatment. 2. Platelet count >= 100 × 109/L without transfusion within 2 weeks (<= 14 days) prior to study treatment. 3. Hemoglobin >= 9 g/dL without transfusion or erythropoietin within 2 weeks (<= 14 days) prior to study treatment. 7. Aspartate transaminase (AST) and alanine aminotransferase (ALT) <= 2.5 × upper limit of normal (ULN), and total bilirubin <= 1.5 × ULN. Exceptions: Patients who have serum bilirubin increases due to documented underlying Gilbert's Syndrome or familial benign unconjugated hyperbilirubinemia may be enrolled. Patients with known liver metastases or patients with hepatocellular carcinoma may be enrolled with AST, ALT, and/or total bilirubin <= 5 × the ULN. 8. Adequate renal function defined by either a creatinine clearance >= 45 mL/min (by Cockcroft-Gault formula) or serum creatinine (SCr) <= 1.5 × ULN 9. Coagulation tests, defined by the following: 1. Activated partial thromboplastin time (aPTT) <= 1.5 × ULN. 2. International normalized ratio (INR) <= 1.5 × ULN. Exception: INR 2 to <= 3 × ULN is acceptable for patients on Warfarin anticoagulation. 10. Left ventricular ejection fraction (LVEF) >= 50% measured by multiple-gated acquisition (MUGA) or echocardiogram (ECHO.). 11. Previous antitumor therapy (including endocrine, chemoradiotherapy/ radiotherapy, targeted therapy, or immunotherapy) that has ended at least 4 weeks prior to administration of ADG116. Focal radiation therapy for symptom relief must have been completed at least 2 weeks prior to the first dose of ADG116. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<= 2 weeks of radiotherapy) to non-CNS disease. Exception: hormonal therapy for prostate cancer is allowed (Section 6.7). 12. Previous AEs have been improved to baseline or Grade <= 1 NCI CTCAE v5.0 (except for patients with alopecia). Participants with Grade <= 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade <= 2 requiring treatment or hormone replacement may be eligible. Exclusion Criteria: * Patients who meet any of the following criteria cannot be enrolled: 1. Pregnant or breastfeeding females. 2. Females of childbearing potential and males whose partners are of childbearing potential who do not agree to the use of 2 forms of highly effective contraception during the treatment period and for 6 months after the last dose of study drug. 3. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug. 4. Grade >= 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior immunotherapy. 5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 6. History of severe hypersensitivity (Grade >= 3) or known to be allergic to protein drugs or recombinant proteins or any ingredients contained in the ADG116 or pembrolizumab drug formulation. 7. Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed. 8. Patients requiring systemic treatment with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive medications within 21 days before the planned first dose of study drug. Ophthalmologic, nasal, inhaled and intra-articular injections of steroids are allowed. 9. Patients receiving granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, or blood (red blood cell [RBC] or platelet) transfusion within 14 days prior to the first dose of the study drug. 10. Any evidence of underlying liver dysfunction due to other causes; Any history of significant alcohol abuse, alcoholic or drug-induced hepatitis, or documented nonalcoholic steatohepatitis. 11. Active viral (any etiology) hepatitis patients are excluded. Hepatitis B virus (HBV) carriers are ineligible. Cured Hepatitis C (HCV) (negative HCV ribonucleic acid [RNA] test) patients may be enrolled after consulting with the Medical Monitor. 12. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled diabetes as evidenced by Screening (baseline) HbA1c>= 7.5, asthma, chronic obstructive pulmonary disease (COPD), or other conditions that pose a risk to the patient participating on study. 13. Has a known history of HIV infection. 14. Patients with any type of primary immunodeficiency or autoimmune disorder requiring treatment. 15. Major surgery within 4 weeks prior to the first dose of the study drug. 16. Has had an allogeneic tissue/solid organ transplant. 17. Clinically significant cardiac conditions, including myocardial infarction within the last 6 months, uncontrolled angina, viral myocarditis, pericarditis, cerebrovascular accident, or other acute uncontrolled heart disease <3 months prior to the first dose of the study drug; LVEF <50%, New York Heart Association (NYHA) Class III or IV congestive heart failure, or uncontrolled hypertension. 18. Patients with underlying hemoglobinopathies (e.g., thalassemia) will be excluded. 19. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug. 20. Has received a COVID-19 vaccine within 7 days prior to the first dose of study treatment. Has received any other live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Administration of killed vaccines are allowed. 21. Has received a positive COVID-19 test within 14 days of Cycle 1 Day 1. 22. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. 23. Any known, documented, or suspected history of illicit substance abuse. 24. Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the Investigator might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the trial or compromise the trial objectives.

Study Objectives This is a randomized multicenter open label phase III factorial trial evaluating the 3 years OS in patients with locally advanced squamous cell carcinoma of head and neck treated with locoregional treatment (radiotherapy plus concomitant chemotherapy or cetuximab) with or without neoadjuvant chemotherapy. Conditions: Head and Neck Squamous Cell Carcinoma Intervention / Treatment: DRUG: RT+CDDP/5-FU, DRUG: RT+CETUXIMAB, DRUG: INDUCTION CTx(TPF)+(RT+CDDP/5-FU), DRUG: INDUCTION CTx(TPF)+(RT+CETUXIMAB) Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: FACTORIAL Masking: NONE

Inclusion Criteria: * Histologically or cytologically proven squamous cell carcinoma of the head and neck. * Primary tumor sites eligible : oral cavity, oropharynx, hypopharynx Although they are admittedly of squamous cell types, the following tumors will be excluded because of them responsiveness to chemotherapy: tumors of the nasal and paranasal cavities and of the nasopharynx. * Stage 3 or 4 disease without evidence of distant metastases verified by chest X Ray, abdominal ultrasound, or CT (liver function test abnormalities); bone scan in case of local symptoms. * At least one uni or bidimensionally measurable lesion. * Tumor considered inoperable after evaluation by a multidisciplinary team (i.e. a surgeon, a medical oncologist and a radiation oncologist). Criteria for inoperability are: 1. technical unresectability: tumor fixation/invasion to base of the skull or cervical vertebrae, involvement of the nasopharynx, and fixed lymph nodes. 2. Physician decision based on low surgical curability. This category will include the following: i) All T3-4 stages. ii) All N2-3 stages excluding T1 N2. iii) Patients for organ preservation. Reason for inoperability will be recorded in the CRF. * No previous chemotherapy or radiotherapy for any reason and no previous surgery for SCCHN (other than biopsy) are allowed at time of study entry. * Age > 18 years. * Karnofsky performance status > 70. (ECOG 0-1) (Appendix II) * No active alcohol addiction. * Life expectancy > 6 months. * Signed informed consent prior to beginning protocol specific procedures. * Adequate bone marrow, hepatic and renal functions as evidenced by the following: a) Hematology (Bone marrow): i) Neutrophils > 2.0 109/L ii) Platelets > 100 x 109/L iii) Hemoglobin > 10 g/dL b) Hepatic function i) Total bilirubin < 1 x UNL ii) ASAT (SGOT) and ALAT (SGPT) < 2.5 x ULN iii) Alkaline phosphatase < 5 x ULN Patients with ASAT or ALAT > 1.5 x ULN associated with alkaline phosphatase > 2.5 x ULN are not eligible for the study. c) Renal function : serum creatinine < 1 x UNL. In case of borderline value the creatinine clearance > 60 ml/min (calculated by the Cockcroft-Gault method as follows : * Patients must be available for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating center. - Exclusion Criteria: * Pregnant or lactating women or women of childbearing potential not using adequate contraception. * Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin, or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years. Any prior treatment with radiotherapy or chemotherapy is an exclusion criterion. * Symptomatic peripheral neuropathy > grade 2 by NCIC-CTG criteria * Symptomatic altered hearing > grade 2 by NCIC-CTG criteria. * Other serious illnesses or medical conditions including: 1. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry. 2. History of significant neurologic or psychiatric disorders including dementia or seizures. 3. Active uncontrolled infection. 4. Active peptic ulcer. 5. Hypercalcemia. 6. Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry * History of hypersensitivity reaction to polysorbate 80 (Appendix IV) * Patients requiring intravenous alimentation. * Patients who experienced a weight loss of more than 20% of their body weight in the 3 months preceding study entry. * Concomitant treatment with any other anticancer therapy. * Participation in a therapeutic clinical trial within 30 days of study entry

Study Objectives The investigators conducted a prospective un-blinded pilot study of Vitamin D plus Calcium (Ca) supplementation in overweight (BMI \> 27) premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), as defined by the Rotterdam Criteria, 2003, and who were deficient in vitamin D as reflected by serum 25-hydroxy (25-OH) vitamin D (serum levels \< 20 ng/mL). Conditions: Polycystic Ovarian Syndrome, Vitamin D Deficiency Intervention / Treatment: DIETARY_SUPPLEMENT: Vitamin D2 (Ergocalciferol), DRUG: Medroxyprogesterone (Provera), DIETARY_SUPPLEMENT: Vitamin D3 (Cholecalciferol), DIETARY_SUPPLEMENT: Elemental Calcium 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: * Premenopausal women (ages 18-40 years) with normal thyroid function and prolactin levels. * PCOS diagnosis based on Rotterdam criteria: presence of at least 2 of the following criteria: * oligomenorrhea-menstrual cycles > 35 day intervals * hyperandrogenemia (elevated serum testosterone [free or total] &/or androstenedione levels) or features of hyperandrogenism i.e. acne or hirsuitism [Ferriman-Gallaway score > 3] * polycystic ovaries on vaginal ultrasound as defined by ESHRE/ASRM criteria (ovarian volume >= 10mL or >= 12 follicles of diameter between 2-9mm in at least one ovary) * Overweight (BMI >= 27 Kg/m2) * Biochemical evidence of Vitamin D insufficiency (i.e. serum 25 OHD levels < 20ng/mL) Exclusion Criteria: * Pregnancy * Known causes of oligomenorrhea other than PCOS, e.g. hypothyroidism/Cushing's Disease/late onset congenital adrenal hyperplasia (fasting 17-alphahydroxyprogesterone levels < 200ng/dL) * Use of hormonal treatment (birth control pill/patch/depot medroxyprogesterone/medroxyprogesterone) within 3 months of the study onset. * Use insulin sensitizers (metformin, sulfonylureas, TZDs, incretins) within 3 months of the study onset. * Use of lipid lowering agents or medications known to influence insulin sensitivity (e.g. niacin, corticosteroids, beta blockers, calcium channel blockers, thiazide diuretics) or influence serum androgens (estrogen, anti-androgens, androgens) within 3 months of the study onset. * Known history of renal calculi or current use of Calcium and Vitamin D supplements. * Spanish Speaking.

Study Objectives The purpose of this study is to assess the efficacy of ZD6474 in patients with metastatic breast cancer at 2 dose levels. Conditions: Breast Neoplasms, Metastases, Neoplasm Intervention / Treatment: DRUG: ZD6474 Location: United States, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: FACTORIAL Masking: NONE

Inclusion Criteria: * Histological and/or cytological confirmation of metastatic breast cancer which is refractory to anthracycline, taxane, with or without capecitabine therapies; * WHO performance status 0, 1 or 2 on the day of registration; * Females, aged >= 18 years; * No Gastrointestinal pathology which could affect the bioavailability of ZD6474. Exclusion Criteria: * Any evidence of severe or uncontrolled systemic diseases including known cases of Hepatitis B or C or human immunodeficiency virus (HIV). * Significant cardiac event (including symptomatic heart failure or unstable angina) within 3 months of entry or any cardiac disease that in the opinion of the investigator increases risk for ventricular arrhythmia; * History of clinically significant cardiac arrhythmia (multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTC grade 3) or asymptomatic sustained ventricular tachycardia; * Chronic atrial fibrillation; * Previous history of QT / QTc prolongation with other medication; * Congenital long QT syndrome; * Systemic anti-cancer therapy or other investigational agent within the last 4 weeks (6 weeks for nitrosoureas, mitomycin C, or suramin); * Currently receiving drugs with known significant 3A4 inhibitory (ie, ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil) or stimulatory (ie, phenytoin, carbamazepine, barbiturates, rifampicin) effects; * Currently receiving therapeutic doses of warfarin (Coumadin?)

Study Objectives The purpose of this research study is to learn about the safety and effectiveness of the study drug, PF-06688992. Before this study, PF-06688992 has never been given to people. PF-06688992 is a targeted therapy for people with cancer. The investigators linked a chemotherapy drug to an antibody (protein found in the blood). The antibody will connect to GD3 which is found on most melanomas but on very few other cells in the body. The investigators hope that in this way, it will deliver this chemotherapy directly to the melanoma and not to normal tissues. Conditions: Melanoma Intervention / Treatment: DRUG: PF-06688992 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: * Histological diagnosis of melanoma confirmed at MSKCC * Measurable unresectable Stage III or IV Malignant Melanoma and Response Criteria in Solid Tumors [RECIST], Version 1.1. * Patients must have progressed on prior approved checkpoint inhibitor therapy, not tolerated approved checkpoint inhibitor therapy, or have a contraindication to approved checkpoint inhibitors. Patients with stable disease after approved checkpoint inhibitor therapy will also be eligible. * Patients whose melanomas harbor a BRAF V600E or V600K mutation must have progressed on a RAF inhibitor. Patients who had to discontinue RAF inhibitor therapy because of toxicity but who did not progress will be eligible unless they responded to therapy. In that case, they will not be eligible unless they progress. * Age >= 18 years * ECOG performance status 0-1. * Adequate Bone Marrow Function as defined by: °>=1,500/mm^3 or >= 1.5 x 10^9/L; * Platelets >= 100,000/mm3 or >= 100 x 109/L; * Hemoglobin >= 9 g/dL. * Adequate Renal Function as defined by: * Serum creatinine <= 1.5 x upper limit of normal (ULN); or * Estimated creatinine clearance >= 60 mL/min as calculated using the method standard for the institution. * Adequate Liver Function as defined by: * Total serum bilirubin <= 1.5 x ULN unless the patient has documented Gilbert syndrome; * Aspartate and Alanine Aminotransferase (AST & ALT) <= 2.5 x ULN; <= 5.0 x ULN if there is liver involvement secondary to tumor; * Alkaline phosphatase <= 2.5 x ULN; (<= 5 x ULN in case of bone metastasis). * QTc interval < 470 msec. * Recovery from all prior surgical or adjuvant treatment-related toxicities, to Baseline status, or a CTCAE Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia. Post-surgical pain will not be considered a basis for exclusion. * Negative serum/urine pregnancy test (for women of childbearing potential). * Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. * Evidence of a signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. * Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures. Exclusion Criteria: * Patients with known symptomatic brain metastases requiring steroids. * Patients with previously diagnosed brain metastases are eligible as long as they do not require CNS-directed therapy (including corticosteroids). If the patient has had radiation therapy or surgery, then they should have completed treatment and have discontinued corticosteroids for at least 2 weeks and must be neurologically stable. * Patients with uveal melanoma will not be eligible as these tumors show low expression of GD3. * Major surgery, radiation therapy or systemic anti-cancer therapy within 2 weeks of starting study treatment. * Presence of >= Grade 2 peripheral neuropathy. * Significant prior infusion reaction to monoclonal antibodies that required treatment with systemic steroids. * Active and clinically significant bacterial, fungal or viral infection. * Known infections with hepatitis B (HBV) or hepatitis C (HCV), * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness not controlled (with undetectable viral load) on HAART therapy. Patients on HAART with undetectable viral loads may be eligible per PI judgment. * Pregnant or breastfeeding; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after last dose of investigational product. * Patients currently receiving active treatment for melanoma. * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack. * Any ongoing cardiac dysrhythmias of NCI CTCAE Grade >2, NCI CTCAE Grade 4 atrial fibrillation, or QTcF interval >470 msec, except for documented Right Bundle Branch Block, at screening. * Chronic Bronchitis or Emphysema requiring oxygen therapy within the last 6 months. * Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality or uncontrolled hypertension that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Study Objectives The primary objective of this study is to evaluate the safety and effectiveness of balloon kyphoplasty treatment for painful, acute, vertebral compression fractures (VCFs) as compared to standard non-surgical therapy in patients with cancer. Conditions: Cancer, Spinal Fractures Intervention / Treatment: DEVICE: Balloon Kyphoplasty, OTHER: Non Surgical Management Location: Hungary, Germany, Canada, United Kingdom, United States, Belgium, Australia, Sweden Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * One to 3 painful (pain on palpation/percussion over fractured vertebral body) VCF(s), T5-L5, with either bone marrow edema imaged by magnetic resonance imaging (MRI) or a fracture imaged by plain radiographs using the method of Genant * Pain NRS score >=4 on a scale of 0 to 10 * When the patient is newly diagnosed with multiple myeloma, the pain assessment must not be done until after completion of at least one pulse of steroid therapy or one week after the initiation of active multiple myeloma therapy. * Roland Morris Disability Questionnaire score >= 10 on a scale of 0 to 24 * Patients must be at least 21 years old. * No change in chemotherapy regimen (change in dose(s) permitted) for 1 month prior to enrollment * No change in chemotherapy regimen (change in dose(s) permitted) planned for at least 1 month following enrollment * No major surgery to the spine planned for at least 1 month following enrollment * Life expectancy of >= 3 months * Patient has sufficient mental capacity to comply with the protocol requirements * Patient has stated availability for all study visits * Patient is able to understand the risks and benefits of participating in the study and is willing to provide written informed consent. Exclusion Criteria: * Patients with primary tumors of the bone (e.g., osteosarcoma) or solitary plasmacytoma at site of the index VCF. Patients with these tumors in anatomic sites other than the index VCF are eligible. * Concurrent Phase I investigational anti-cancer treatment * Significant clinical morbidities (aside from the index fracture(s) and cancer) that may potentially interfere with the collection of data concerning pain and function * VCF morphology deemed unsuitable for balloon kyphoplasty * Additional non-kyphoplasty surgical treatment is required for the index fracture * Patients requiring the use of high-dose steroid (>= 100 mg prednisone or 20 mg dexamethasone per day), intravenous (IV) pain medication, or nerve block to control chronic back pain unrelated to index VCF(s). Patients who receive high-dose steroids for treatment of their cancer (for at least 30 days) are eligible. * Patients with a platelet count of < 20,000 measured at the time of hospital admission for the procedure * Spinal cord compression or canal compromise requiring decompression * Patients with osteoblastic tumors at the site of index VCF. Patients with osteoblastic tumors outside of vertebral levels intended for kyphoplasty may be enrolled. * Medical/surgical conditions contrary to the balloon kyphoplasty procedure (e.g., in the presence of active or incompletely treated local infection) * Known allergy to bone cement or contrast medium used in the treatment of study subjects * MRI contraindication (e.g., cerebral aneurysm clips, pacemaker, implanted biostimulators, cochlear implants, penile prosthesis) * Positive baseline pregnancy test (for women of child-bearing potential) * Patients who may require allogeneic bone marrow transplantation during the course of the study. Other Reasons for Lack of Enrollment: A. Patient is afraid to have surgery B. Patient is afraid to have anesthesia C. Patient/family is not willing to participate in research D. Patient is not willing to be randomized

Study Objectives RATIONALE: Armodafinil may help relieve fatigue and improve quality of life in patients with cancer receiving radiation therapy to the brain. PURPOSE: This clinical trial is studying how well armodafinil works in treating fatigue caused by radiation therapy in patients with primary brain tumors. Conditions: Brain Tumors, Nervous System Tumors, Cognition Disorders, Fatigue Intervention / Treatment: DRUG: Armodafinil, OTHER: placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria * Histologically confirmed primary brain tumor, including any of the following: * Glioblastoma multiforme * Anaplastic astrocytoma * Anaplastic oligodendroglioma * Anaplastic mixed oligoastrocytoma * Low-grade glioma * Meningioma * Ependymoma * Other primary brain tumor histologies * Planning to undergo external-beam cranial radiotherapy (partial- or whole-brain radiotherapy) meeting all of the following criteria: * Total dose >= 4,500 cGy * Total number of fractions >= 25 fractions * Dose per fraction >= 150 cGy PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * Hemoglobin >= 10.0 g/dL (erythropoietin or transfusion allowed for symptomatically anemic patients with a hemoglobin < 10 g/dL) * Creatinine <= 2 mg/dL * Total bilirubin <= 2 times upper limit of normal (ULN) * SGOT and SGPT <= 3 times ULN * Not pregnant or nursing * Negative pregnancy test * Sexually active women of childbearing potential must use a reliable method of birth control * It is recommended that patients use non-hormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with armodafinil * Prior malignancies allowed Exclusion Criteria: * No baseline headaches (i.e., headaches occurring in the week before baseline assessment) of grade 4 severity (defined as severe and disabling headaches, requiring analgesics, and interfering with and preventing function or activities of daily living) * No concurrent uncontrolled illness that may cause fatigue; interfere with drug absorption, distribution, metabolism, or excretion; or limit compliance with study requirements including, but not limited to, any of the following: * Ongoing or active infection * Chronic renal insufficiency * Psychiatric illness (psychosis, psychotic disorder, history of suicide attempt, or actively suicidal) * Extreme social situations (e.g., transportation issues that would preclude study compliance) * Patients with a history of cardiac issues (symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia) should not use armodafinil as it may cause chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG * No history of allergic reaction attributed to modafinil or armodafinil * No anticipated or planned excessive consumption of coffee, tea, and/or caffeine-containing beverages averaging > 600 mg of caffeine/day (i.e., approximately 6 cups of coffee/day, 12 cups of hot tea/day, or 12 cans of cola/day) PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior fractionated external-beam cranial radiotherapy * More than 30 days since prior monoamine oxidate inhibitors or investigational drugs * More than 2 weeks since prior and no concurrent modafinil (Provigil), donepezil (Aricept), memantine hydrochloride (Namenda), methylphenidate (Ritalin), dextroamphetamine-amphetamine (Adderall), ginkgo biloba, or any other cognitive function-enhancing drugs * At least 4 weeks since prior and no concurrent interstitial or intracavitary chemotherapy and/or radiotherapy or stereotactic radiosurgery (i.e., Gamma Knife, Linac, or Cyberknife) * No concurrent erythropoietin, transfusion, or iron therapy (unless patient is symptomatically anemic with hemoglobin < 10 g/dL) * Concurrent chemotherapy allowed * Concurrent hormonal therapy for other malignancies allowed * No concurrent non-hormonal therapy (e.g., Herceptin and other targeted agents), or cytotoxic chemotherapy * No concurrent clopidogrel bisulfate (Plavix)

Study Objectives This phase II trial studies how well TG4010 and nivolumab work in previously treated patients with non-small cell lung cancer. Vaccines that are made from a gene-modified virus, such as TG4010, may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as nivolumab, interfere with the ability of tumor cells to grow and spread. Giving TG4010 and nivolumab together may work better in previously treated patients with non-small cell lung cancer. Conditions: Recurrent Non-Small Cell Lung Carcinoma, Stage I Non-Small Cell Lung Cancer, Stage II Non-Small Cell Lung Cancer, Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer Intervention / Treatment: BIOLOGICAL: TG4010, BIOLOGICAL: Nivolumab 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 non-squamous NSCLC; patients with adenocarcinoma must have had epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational testing; those with an actionable mutations/rearrangements are excluded * Stage IIIB or IV patients must have progressed after a platinum based chemotherapy; a maximum of 3 previous systemic regimens are allowed (one regimen can be a tyrosine kinase inhibitor); patients with stage I-IIIB NSCLC who have progressed within 6 months of a full dose platinum based regimen as adjuvant therapy or with radiotherapy are eligible; patients who received weekly low dose chemotherapy with radiation only are not eligible * At least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) based on RECIST version 1.1 * Performance status (PS) 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale * Minimum life expectancy of 3 months * Hemoglobin >= 10.0 g/dL * White blood cells (WBC) >= 3.0 x 10^9/L * Neutrophils >= 1.5 x 10^9/L * Total lymphocyte count >= 0.5 x 10^9/L * Platelet counts >= 100 x 10^9/L * Serum alkaline phosphatase =< 3 x upper limit of normal (ULN) in absence of liver or bone metastases and =< 5 x ULN in patients with documented bone or liver metastases * Total bilirubin =< 1.5 x ULN * Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) =< 2.5 x ULN in the absence of liver metastases and =< 5 x ULN in case of liver metastases * Glomerular Filtration Rate >= 60 mL/min (according to Modification of Diet in Renal Disease [MDRD] formula or Cockcroft & Gault formula) * Serum albumin >= 30 g/L * Effective contraception during the study period and for 5 months after the last study treatment administration (male and female patient) * Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll * Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * Patients having active central nervous system (CNS) metastases; patients adequately treated and neurologically returned to baseline (except for residual signs of symptoms related to the CNS treated) for at least 2 weeks prior to enrolment are allowed; in addition, patients must be either off corticosteroids or on a stable or decreasing dose of < 10 mg daily prednisone or equivalent * Prior exposure to cancer immunotherapy including any immune checkpoint inhibitor and/or cancer vaccines * Prior history of other malignancy except: * Basal cell carcinoma of skin * Cervical intra-epithelial neoplasia * Other cancer curatively treated with no evidence of disease for at least 2 years * Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs (e.g. cyclosporine) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to start of the study treatment (day 1 [D1] of cycle 1) * Positive serology for human immunodeficiency virus (HIV) or hepatitis C virus (HCV); presence in the serum of the antigen hemoglobin (HBs) * Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g. elevated troponin or creatinine, uncontrolled diabetes) * Patients with major surgery or radiotherapy within 4 weeks prior to the start of the study treatment (i.e. D1 of cycle 1); however, prior surgery or radiation therapy aimed at local palliation or attempted local disease control (except in case of thoracic radiotherapy) is permitted but has to be completed one week before treatment start * Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 10 mIU/mL); pregnancy is ruled out by a beta hCG test completed if necessary with an ultrasound * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are: * Women whose sexual orientation precludes intercourse with a male partner * Women whose partners have been sterilized by vasectomy or other means * Using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices [IUDs]; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable) * Patient with an organ allograft * Known allergy to eggs, gentamicin, or platinum containing compounds * Hypersensitivity to the active substance or to any of the excipients * Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment (i.e. D1 of cycle 1) * Patient unable or unwilling to comply with the protocol requirements * Subject has active, known or suspected autoimmune disease, including systemic lupus erythematodes, Hashimoto thyroiditis, scleroderma, polyarteritis nodosa, or autoimmune hepatitis * Subject has any peripheral neuropathy >= National Cancer Institute (NCI) CTCAE grade 2 at enrollment * Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies; any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity * History of any of the following cardiovascular conditions within 12 months of enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association * Left ventricular ejection fraction (LVEF) less than the lower limit of normal (LLN) as assessed by echocardiography

Study Objectives To investigate the benefits and risks of maintenance chemotherapy (MCT), maintenance endocrine therapy (MET) and none maintenance therapy after first-line treatment of metastatic breast cancer (MBC). Conditions: Metastatic Breast Cancer Intervention / Treatment: DRUG: Capecitabine, DRUG: Liposomal doxorubicin, DRUG: Gemcitabine, DRUG: Fulvestrant, DRUG: Anastrozole, DRUG: Letrozole Location: China Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with pathologically clear invasive breast cancer between 2003 and 2018; * Female,18-75 years old; * Measurable metastatic lesion according to RECIST 1.1 evaluation criteria; * The first-line chemotherapy regimen is a breast cancer combination or single-agent chemotherapy regimen recommended by the NCCN guidelines; * First-line chemotherapy is effective (according to RECIST1.1 evaluation criteria, the efficacy is evaluated as complete response (CR), partial response (PR), or steady state (SD)); * After the last cycle of first-line chemotherapy, patients should still be in a state of no progress for at least 4 weeks; * Patients' Karnofsky performance status (KPS) scores were >=70. Exclusion Criteria: * Unmeasurable metastatic lesion according to RECIST 1.1 evaluation criteria.

Study Objectives To determine the impact of maintenance therapy in patients with MDS/AML in remission. Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndrome Intervention / Treatment: DRUG: Azacitidine, BIOLOGICAL: Sargramostim 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: * Age > 6 months * Initial diagnosis of poor -risk AML or MDS (defined in section 3.2), treated with either stem cell transplant or cytarabine-based consolidation chemotherapy, within the past 60-185 days * ECOG performance status 0-2 * No morphologic evidence of leukemia or active MDS as determined by JHH Hematopathologist independent review of a bone marrow aspirate and biopsy done following the completion of therapy and within 14 days prior to enrollment * Peripheral blood count recovery: Neutrophil count >= 1000 /µL, platelet count >= 50x 109 /µL without platelet transfusions, and adequate hematocrit independent of red cell transfusions . * No evidence of extramedullary leukemia, such as CNS or soft tissue involvement * Adequate end organ function as measured by the following: AST and ALT < 4 x normal, total serum bilirubin < 2 x upper limit normal (unless due to hemolysis, Gilbert's syndrome, or ineffective erythropoiesis), creatinine < 2 x upper limit of normal * Ability to give informed consent * In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile Exclusion Criteria: * Patients with untreated or uncontrolled infections * Patients with untreated or uncontrolled grade 3 or 4 GVHD * Pregnancy and lactation * Concurrent use of any other investigational agents. * Known HIV-positive patients. * Known hypersensitivity to 5AC or GM-CSF

Study Objectives To compare the efficacy, acceptability and safety of the new 2 liter gut cleansing solution (Moviprep) and NaP preparation in routine colon cleansing prior to tumor screening colonoscopies Conditions: Colonoscopy Intervention / Treatment: DRUG: Macrogol 3350 Na sulphate NaCl KCl Ascorbic Acid Na Ascorbate, DRUG: Sodium Phosphate solution (NaP) Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * The subject's written informed consent had to be obtained prior to inclusion. * Male or female ambulatory subjects with an age of 18 to 85 years planned to undergo a complete colonoscopy for colon cancer screening * Willing, able and competent to complete the entire procedure and to comply with study instructions * Females of childbearing potential had to employ an adequate method of contraception Exclusion Criteria: * Ileus * Intestinal obstruction or perforation * Toxic megacolon * History of colonic resection * Requirement for permanent medication and associated stable serum concentrations (e.g. neuroleptic drugs) * Congestive heart failure (NYHA III + IV) * Acute life threatening cardiovascular disease * Untreated or uncontrolled arterial hypertension (max. > 170 mmHg and min > 100 mmHg) * Known moderate to severe renal insufficiency * Severe renal failure * Severe liver failure * Known glucose 6 phosphatase dehydrogenase deficiency * Known phenylketonuria * Known hypersensitivity to polyethylene glycols, NaP and/or Vitamin C * Concurrent participation in an investigational drug study or participation within 30 days of study entry * Females who were pregnant, nursing or planning a pregnancy. Females of child bearing potential not using reliable methods of contraception * Subject had a condition or was in a situation, which in the investigators opinion might have put the subject at significant risk, might confound the study results, or might interfere significantly.

Study Objectives The main goal of this clinical trial is to test if adding pertuzumab (Perjeta), improves the anticancer activity of the combination chemotherapy regimen of trastuzumab (Herceptin) concomitant with paclitaxel, 5-fluorouracil, epirubicin, and cyclophosphamide (T-FEC). The study will also test the safety of this therapy. Conditions: Her2-Positive Breast Cancer Intervention / Treatment: DRUG: Pertuzumab, DRUG: Trastuzumab, DRUG: Paclitaxel, DRUG: 5-fluorouracil, DRUG: Epirubicin, DRUG: Cyclophosphamide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment following NCCN practice guidelines. HER2 overexpression or amplification will be based on local test results and is defined as either: (i) IHC staining of 3+ (uniform, intense membrane staining) in greater than or equal to 10% of invasive tumor cells or, (ii) Fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or, (iii) FISH ratio (HER2 gene signals to chromosome 17 signals) of greater than or equal to 2.0. * Patients with synchronous bilateral breast cancers are eligible if at least one of the tumors is HER2-positive. * Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA, or within the institution's normal limits. * Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG) prior to initiation of chemotherapy. Both female and male breast cancer patients who are sexually active have to agree to practice contraception while participating in the trial and for 3 month after completion of therapy. * Adequate bone marrow function as indicated by the following: * ANC greater than or equal to 1500/uL * Platelets greater than or equal to 100,000/uL * Hemoglobin greater than or equal to 10 g/dL * Adequate renal function, as indicated by creatinine less than or equal to 1.5 times upper limit of normal (ULN) * Adequate liver function, as indicated by bilirubin less than or equal to 1.5 X ULN and AST or ALT less than or equal to 2x ULN. * Signed informed consent. Exclusion Criteria: Patients will be excluded from the study based on any of the following criteria: * Patients who underwent partial excisional biopsy, lumpectomy, segmental mastectomy, modified radical mastectomy or sentinel node biopsy and, therefore cannot be assessed for pathologic response accurately. * Patients who are high risk for developing the following anthracycline, paclitaxel, trastuzumab or pertuzumab related toxicities including: History of congestive heart failure, myocardial infarction or cardiomyopathy, uncontrolled hypertension despite adequate medications Pre-existing peripheral neuropathy > grade 3 Prior anthracycline therapy Known hypersensitivity to any of the study medications Patients older than age 65 due to increased risk of cardiotoxicity * Active infection requiring systemic antibiotic therapy. * Pregnant or lactating women

Study Objectives This will be a randomized blinded clinical trial. Patients will be randomized to receive either a remifentanil or dexmedetomidine infusion for general anesthesia. The anesthesia team will know the result of randomization at induction. Data will be gathered by research personnel who will be blinded to the anesthetic method used. Patients will be blinded to the anesthetic they receive till they are discharged from the PACU when they will have the option to be unblinded. The Data Safety and -Toxicity Committee will review all serious adverse events and toxicity reports as well as annual reviews. Conditions: Adult Intracranial Tumor, Adult Solid Tumor Intervention / Treatment: DRUG: Remifentanil, DRUG: Dexmedetomidine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: Patients who undergo general anesthesia for elective surgical excision of a brain tumor with following specifications: * Age: >= 18 years * Primary and redo cases will be included * Duration of surgery not exceeding 6 hrs. Exclusion Criteria: * Patient refusal * Emergency craniotomy * Morbid obesity * Uncontrolled hypertension - DBP more than 110 * Cardiac conduction defects * Patients with chronic pain.

Study Objectives A non-interventional, post authorization safety study to evaluate the safety of Kineret in the treatment of Cryopyrin Associated Periodic Syndromes (CAPS) in routine clinical care with regard to serious infections, malignancies, injection site reactions, allergic reactions and medication errors, including re-use of syringe. Conditions: Cryopyrin-Associated Periodic Syndromes Intervention / Treatment: DRUG: anakinra (Kineret) Location: Netherlands, United Kingdom Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Informed consent by the patient and/or caregiver * Kineret treatment will be according to the Summary of Product Characteristics (SmPC), as confirmed by the Investigator Exclusion Criteria: * None

Study Objectives This phase II trial is studying how well sorafenib works in treating patients with extensive stage small cell lung cancer. Sorafenib may stop the growth of small cell lung cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Conditions: Extensive Stage Small Cell Lung Cancer, Recurrent Small Cell Lung Cancer Intervention / Treatment: DRUG: sorafenib tosylate 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 diagnosis of small cell lung cancer and must have extensive disease with progression or recurrence after receiving a standard first-time regimen containing either cisplatin or carboplatin; patients who receive primary curative chemoradiation therapy for limited disease, but who recur within the primary tumor site, previously radiated field or with distant metastases are also allowed to participate; diagnosis based on sputum cytology is acceptable if confirmation by an independent pathologic review at the institution is documented; patients who have clinical evidence of recurrent small cell lung cancer do not require a confirmatory biopsy to be eligible for this trial * Patients must have measurable disease per RECIST criteria; patients must have evidence of disease by plain radiographs, CT scan or MRI scan; all x-rays/scans to assess measurable disease must have been performed within 28 days prior to registration; all other required test to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed * Patients must have been previously treated with exactly one regimen; this must have included cisplatin or carboplatin; in addition, information must be available to place the patient in one of the two following categories: * Platinum sensitive disease: defined as an initial response to platinum-based chemotherapy who subsequently progressed > 90 days after last platinum treatment; best response to platinum-based treatment: CR, PR, stable or progression while on treatment (circle one); NOTE: Prior chemotherapy must have been completed at least 90 days prior to registration OR * Platinum refractory disease; no response to platinum-based chemotherapy, progression during platinum-based therapy, or progression within 90 days of completing platinum-based therapy * Patient may have receive previous radiation therapy, but it must have been completed at least 21 days prior to registration and the patient should have recovered from all associated toxicities; there must be no plans for the patients to receive concurrent radiation therapy to measurable lesions; measurable disease may be present inside the area of prior radiation therapy provided that the lesion is demonstrated to be progressing by CT scan or there is measurable disease outside the prior radiation field * Patients may have received prior surgery provided that at least 14 days have elapsed since surgery (thoracic or other major surgeries) and the patient has recovered from all associated toxicities; patients must have disease outside the area of previous surgical resection or a new lesion must be present * CORRELATIVE SCIENCE STUDIES: Institutions must have IRB approval of S9925 (the Lung Cancer Specimen Repository); patients must be offered participation in S9925; with the patient's consent, specimens will be submitted for testing via S9925; patients must be registered separately to S9925 in order for institutions to receive credit for specimen submission * Serum creatinine =< the institutional upper limit of normal OR creatinine clearance >= 60 cc/min * Bilirubin =< 2 x the institutional upper limit of normal * Alkaline phosphatase =< 2 x the institutional upper limit of normal * SGOT or SGPT =< 2 x the institutional upper limit of normal * PTT and either PT or INR < 1.5 x the institutional upper limit of normal (except in patients who are on warfarin [Coumadin or heparin] obtained within 28 days prior to registration); patients who receive anti-coagulation treatment with an agent such as warfarin or heparin, prophylactically or therapeutically, will be allowed to participate * Patients must not have any evidence of bleeding diathesis * ANC >= 1,500/uL * Platelet count >= 100,000/uL * Patients must have a Zubrod performance status 0-1 * Patients with known brain and/or leptomeningeal metastases are eligible only if he/she is asymptomatic, without deficits on neurologic exam and is not receiving corticosteroid therapy to control symptoms; only a non-enzyme inducing anticonvulsant (e.g., Keppra) will be permitted for those patients requiring anticonvulsants; all patients must have a pretreatment CT or MRI scan of the brain to evaluate CNS disease within 28 days prior to registration * Any ongoing requirement for systemic corticosteroid therapy is not permitted; topical and/or inhaled steroids are allowed * Patients must either be able to swallow and/or receive enteral medications via gastrostomy feeding tube; patients with intractable nausea or vomiting are not eligible; patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis) are not eligible * The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Patients must not have a significant history of cardiac disease, e.g., uncontrolled hypertension, unstable angina, congestive-heart failure, and myocardial infarction within the last six months, or cardiac ventricular arrhythmias requiring medication * Patients must be willing to provide prior smoking history * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Study Objectives The investigators want to develop a gene expression profile for the prediction of immunotherapy response of patients with metastatic breast cancer presenting malignant pleural effusion. Conditions: Breast Neoplasms, Neoplasm Metastasis, Gene Expression Profiling, Immunotherapy Intervention / Treatment: BIOLOGICAL: cytokine Location: China Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients should be histologically confirmed with metastatic breast cancer and malignant pleural effusion * an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; * At least one measurable lesion; * Normal cardiac, hepatic, renal and bone marrow functions; * Life expectancy >=3 months; * Discontinuity of previous chemotherapy for a minimum of 4 weeks. * Not receive chemotherapy in pleural cavity Exclusion Criteria: * previous history of other malignancies; * previous surgery history on the needle biopsy organ; * Serious or uncontrolled concurrent medical illness.

Study Objectives This is a multicenter, prospective, randomized, open-label phase II study evaluating the efficacy and safety of PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Patients will be randomized to receive * paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or * paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen. Conditions: Breast Cancer, Triple Negative Breast Neoplasms, HRpos Breast Neoplasms, BRCA 1 /2 and / or HRD Intervention / Treatment: DRUG: PwO, DRUG: PwCb, DRUG: EC, PROCEDURE: Surgery after neoadjuvant Therapy, OTHER: Stratification Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Written informed consent for all study specific procedures according to local regulatory requirements prior to beginning specific protocol procedures. * Complete baseline documentation must be sent to GBG Forschungs GmbH. * Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint. * Centrally confirmed negative HER2-status. Centrally confirmed estrogen and progesterone receptor, and Ki-67 status detected on core biopsy. ER/PR positive is defined as >=1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridisation (ISH) ratio >=2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization. * Centrally confirmed tumor Homologous Recombinant Deficiency score (tBRCA positive/mutated and/or HRD high). Patients with known gBRCA and/or tBRCA status can be enrolled prior to the central test results available. * Tumor lesion in the breast with a palpable size of > 2 cm or a sonographical size of >1 cm in maximum diameter. If the tumor is not detectable with sonography mammography assessment can be considered. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion. * Patients must be in the following stages of disease: * cT2 - cT4a-d or * cT1c and cN+ or cT1c and pNSLN+ or * cT1c and ER-neg and PR-neg or * cT1c and Ki67>20% In patients with multifocal or multicentric breast cancer, the largest lesion should be measured and at least one lesion has to meet the above criteria * Age > 18 years. * Karnofsky Performance status index >= 80%. * Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution. * Laboratory requirements: Hematology * Absolute neutrophil count (ANC) >=2.0 x 109 / L and * Platelets >=100 x 109 / L and * Hemoglobin >=10 g/dL (>= 6.2 mmol/L) Hepatic function * Total bilirubin >=1.5x UNL and * ASAT (SGOT) and ALAT (SGPT) >=1.5x UNL and * Alkaline phosphatase >=2.5x UNL. * Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential. * Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (>=21 days, and in no case exceed 6 weeks prior to randomization) (Note MRI/ CT scan may be used as an alternative imaging technique). In case of high risk according to guidelines: chest X-ray (PA and lateral) or as an alternative breast MRI/CT, abdominal ultrasound or CT scan or MRI, and bone scan in case of high risk for primary metastasis according to guidelines. In case of positive bone scan, bone X-ray or CT scan is mandatory. Other tests may be performed as clinically indicated. * Male or female patients * Patients must be available and compliant for central diagnostics, treatment and follow-up. Exclusion Criteria: * Prior chemotherapy for any malignancy within 5 years. * Prior radiation therapy for breast cancer within 5 years. * Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment. * Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy). * Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer). * Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease. * History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent. * Patients currently in an institution by order of jurisdictional or governmental grounds. * Currently active infection. * Definite contraindications for the use of corticosteroids. * Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol. * Concurrent treatment with: * chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent). * sex hormones. Prior treatment must be stopped before study entry. * other experimental drugs or any other anti-cancer therapy. * Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry. * Prior use of a PARP-Inhibitor

Study Objectives The purpose of this study is to assess the effect of a moderate Cytochrome P450 (CYP) 3A inhibitor (erythromycin) and a strong CYP3A inhibitor (voriconazole) on the steady-state pharmacokinetics (PK \[the study of the way a drug enters and leaves the blood and tissues over time\]) of repeated oral doses of ibrutinib in participants with B-cell malignancy (cancer or other progressively enlarging and spreading tumors). Conditions: B-Cell Chronic Lymphocytic Leukemia Intervention / Treatment: DRUG: Ibrutinib, DRUG: Erythromycin, DRUG: Voriconazole Location: Russian Federation, Spain, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), or Waldenstrom's Macroglobulinemia (WM) * Relapsed or refractory disease after at least 1 prior line of systemic therapy (participants with FL or MZL must have failed anti-CD20 monoclonal antibody containing chemotherapy regimen) * Eastern Cooperative Oncology Group Performance Status score of 0 or 1 * Hematology values within the following limits: a) Absolute neutrophil count (ANC) greater than and equal to (>=) 1.0*10^9 per liter (L); b) Platelets >=50*10^9/L without transfusion support within 7 days; c) Hemoglobin >=8 gram per deciliter (g/dL) without transfusion support within 7 days; d) Prothrombin time /International normalized ratio (PT/INR) less than equal to (<=) 1.5*Upper Limit of Normal (ULN) and activated partial thromboplastin time (aPTT) <=1.5*ULN * Biochemical values within the following limits: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3.0*ULN; b) Total bilirubin <=1.5*ULN (unless due to Gilbert's syndrome); c) Serum creatinine <=1.5*ULN or a calculated creatinine clearance of >=50 milliliter per minute per 1.73 square meter Exclusion Criteria: * Major surgery within 4 weeks of the first dose of ibrutinib * Diagnosed or treated for malignancy other than the indication under study except for: a) Adequately treated non-melanoma skin cancer or lentigo maligna, curatively treated in-situ cancer without evidence of disease; b) Malignancy treated with curative intent and with no known active disease present for >=3 years before the first dose of ibrutinib * History of stroke or intracranial hemorrhage within 6 months prior to the first dose of ibrutinib * History of galactose intolerance * Requires anticoagulation with warfarin or equivalent vitamin K antagonists (for example, phenprocoumon)

Study Objectives Many people treated for cancer receive oral chemotherapy medications for their illness. This means that much of their cancer care occurs at home, away from a traditional oncology care setting. The purpose of this study is to explore how a Smartphone mobile application ("mobile app") can help improve the cancer treatment process in people who are prescribed oral chemotherapy medication. The investigators will explore how well the mobile app helps patients stay connected with their oncology care team, take their oral medications as prescribed, and manage their cancer-related symptoms from home. This study will be done in two phases: 1) a pilot phase to assess the feasibility of a mobile application intervention, and 2) a randomized-controlled trial to test the intervention. Conditions: Adherence to Medication Regime, Cancer Intervention / Treatment: OTHER: Mobile Application Intervention Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: Patient Participant Inclusion Criteria * Age greater than 18 years * Diagnosis of cancer with a new or existing prescription for oral chemotherapy * Receiving cancer care at either Massachusetts General Hospital Cancer Center or community affiliates (North Shore or Emerson Hospitals) * Eastern Cooperative Oncology Group (ECOG) ranging from 0 (asymptomatic) to 2 (symptomatic and in bed >50% of the day) * Able to read and respond to questions in English * Uses smart mobile phone (either operating system (iOS) [iPhone] or Android device) Clinician Participant Inclusion Criteria - Clinician participants must be oncology clinicians (i.e. physicians and nurse practitioners) who maintain at least 25% clinical practice at the Massachusetts General Hospital Cancer Center or one of its community affiliates at the North Shore or Emerson Hospital. Stakeholder Participant Inclusion Criteria - Four groups of stakeholders will provide ongoing feedback about the study design, methods, and results. To be eligible as a stakeholder, the participant must be able to represent the interests and perspective of at least one of the following stakeholder groups: * Oncology Patient or Family Member * Oncology Clinician (e.g., Physician or Nurse Practitioner) * Cancer Practice Setting Administrator Health System, Community, and Society. Exclusion Criteria: Patient Participant Exclusion Criteria * Individuals with co-morbid acute or untreated psychiatric symptoms (e.g., psychosis) or neurologic dysfunction will be excluded given that such symptoms would interfere with consent and participation. * Individuals who own Windows or Blackberry smart mobile phones will not be eligible.

Study Objectives This open-label, randomized, cross-over study will evaluate the effect of food on the pharmacokinetics of single oral doses of RO5045337 in patients with solid tumors. The anticipated time on study treatment is 3 weeks. Conditions: Neoplasms Intervention / Treatment: DRUG: RO5045337 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Adult patients, >=18 years of age * Histologically confirmed solid tumor * Life expectancy of >=12 weeks * ECOG performance status of 0 or 1 * Adequate bone marrow, renal and hepatic function Exclusion Criteria: * Patients receiving any other investigational agent or therapy administered with the intention to treat their malignancy within 28 days prior to study start * Patients with pre-existing gastro-intestinal disorder * Patients with uncontrolled intercurrent illness

Study Objectives Anti-EGFR-immunoliposomes loaded with doxorubicin (C225-ILs-dox) are given intravenously in patients with relapsed or refractory high-grade gliomas. The pharmacokinetics of C225-ILs-dox in peripheral blood (PB), cerebro-spinal fluid (CSF) and resected tumour tissue will be assessed. Conditions: Glioblastoma Intervention / Treatment: DRUG: C225-ILs-dox Location: Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written informed consent according to International Conference on Harmonization (ICH)/Good Clinical Practice (GCP) regulations before registration and prior to any trial specific procedures * Patients with relapsed histologically proven glioblastoma >= 18 years of age. * Patients need to have at least one line of treatment with combined radio-chemotherapy * EGFR amplification. EGFR amplification will be tested by comparative genomic hybridization (CGH) method. EGFR will be considered amplified if the value is 0.15 above the average signal of chromosome 7. * Evaluable disease on MRI brain scan * Adequate bone marrow function: neutrophils >= 1.5 x 109/L, platelets >= 100 x 109/L * Adequate hepatic function: bilirubin <= 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST), Alanin-Aminotransferase (ALT) and alkaline phosphatase (AP) <= 2.5 x ULN * Adequate renal function: serum creatinine <= 1.5 x ULN and calculated creatinine clearance > 30 mL/min, according to the formula of Cockcroft-Gault * Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) >= 50% as determined by either echocardiography (ECHO) or radionuclide angiocardiography (MUGA) in addition to pre- (brain-type natriuretic Peptide) BNP from peripheral blood * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours). * No contraindications for lumbar puncture * Women with child-bearing potential have to use effective contraception, are not allowed to be pregnant and have to agree not to become pregnant during trial treatment and during the 6 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential. Exclusion Criteria: * History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration except for adequately treated cervical carcinoma in situ and localized non-melanoma skin cancer. * Lack to provide written informed consent * Previous therapy with more than 240 mg/m2 of doxorubicin or more than 450 mg/m2 of epirubicin * Any serious underlying medical condition (at the judgement of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes, etc.) * Breastfeeding and pregnancy * Participation in any investigational drug trial within 4 weeks preceding treatment start * Any concomitant drugs contraindicated when administering Erbitux™ or Caelyx™ according to the Swissmedic-approved product information * Known hypersensitivity to trial drug(s) or to any component of the trial drug(s) * Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Study Objectives This study seeks to evaluate the efficacy, safety and tolerability of elagolix alone and in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. Conditions: Uterine Fibroids, Heavy Menstrual Bleeding Intervention / Treatment: DRUG: Elagolix, DRUG: Placebo for Estradiol/Norethindrone Acetate, DRUG: Estradiol/Norethindrone Acetate, DRUG: Placebo for Elagolix Location: United States, Puerto Rico, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Subject is a premenopausal female at the time of Screening. * Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound (transabdominal ultrasound/transvaginal ultrasound). * Subject has heavy menstrual bleeding associated with uterine fibroids as evidenced by menstrual blood loss > 80 mL during each of two screening menses as measured by the alkaline hematin method. * Subject has negative urine and/or serum pregnancy test in Screening and just prior to first dose. * Subject has an adequate endometrial biopsy performed during Screening, the results of which show no clinically significant endometrial pathology. Exclusion Criteria: * Subject has screening pelvic ultrasound or saline infusion sonohysterography results that show a clinically significant gynecological disorder. * Subject has history of osteoporosis or other metabolic bone disease. * Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis. * Subject has a history of major depression or post-traumatic stress disorder (PTSD) within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder). * Subject is using any systemic corticosteroids for over 14 days within 3 months prior to Screening or is likely to require treatment with systemic corticosteroids during the course of the study. Over the counter and prescription topical, inhaled, intranasal or injectable (for occasional use) corticosteroids are allowed.

Study Objectives The purpose of this study is to evaluate the anti-cancer activity and safety of Bay 43-006, in patients who have Chronic Myelogenous Leukemia that resisted to Gleevec treatment, one of the standard medication administered for these patients. Conditions: Chronic Myelogenous Leukemia Intervention / Treatment: DRUG: Nexavar (Sorafenib, BAY43-9006) Location: United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria:- Have Philadelphia chromosome positive chronic myelogenous leukemia (CML) in chronic phase, as per IBMTR criteria- Have documented hematologic resistance to Gleevec (Imatinib) following a prior hematologic response to Gleevec administered at doses of at least 400 mg/d for at least 3 months.- Have WBC >20 x 109/L at study entry- Have an ECOG performance status. Status of 0, 1 or 2- Have an anticipated survival of at least 16 weeks.- Be able to comply with study procedures and follow-up examinations.- Signed informed consent must be obtained prior to any study specific procedures. Exclusion Criteria:- Congestive heart failure > class II as defined by the New York Heart Association Functional Classification (NYHA)- Cardiac arrhythmias requiring antiarrythmics (excluding beta blockers or digoxin)- Active coronary artery disease or ischemia- History of HIV infection or chronic hepatitis B or C - Active clinically serious infections (> grade 2 NCI-CTC)- Patients with seizure disorder requiring anti-epileptic drugs- History of solid organ allograft

Study Objectives The purpose of this study was to demonstrate superiority of treatment with avelumab plus best supportive care (BSC) versus physician's choice (chosen from a pre-specified list of therapeutic options) plus BSC. Conditions: Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Gastric Cancer Third Line Intervention / Treatment: DRUG: Avelumab, DRUG: Irinotecan, DRUG: Paclitaxel, OTHER: Best Supportive Care (BSC) Location: Germany, Korea, Republic of, Italy, Spain, United States, Belgium, Australia, Czechia, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male or female subjects aged greater than or equal to (>=) 18 years * Subjects with histologically confirmed recurrent unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ) * Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor tissue * Subjects must have received 2 prior courses of systemic treatment for unresectable, recurrent, locally advanced or metastatic gastric cancer, and must have progressed after the second line * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial entry * Adequate hematological, hepatic and renal functions defined by the protocol * Negative blood pregnancy test at Screening for women of childbearing potential. * Highly effective contraception for both male and female subjects if the risk of conception exists Other protocol defined inclusion criteria could apply Exclusion Criteria: * Prior therapy with any antibody or drug targeting T-cell coregulatory proteins * Concurrent anticancer treatment * Major surgery * Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to less than [<] 10 mg prednisone daily). * All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) * Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder,cervical, colorectal, breast) * Prior organ transplantation, including allogeneic stem-cell transplantation Significant acute or chronic infections * Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent * Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma) * Persisting toxicity of grade >2 related to prior therapy except neuropathy and alopecia * Neuropathy Grade greater than or equal (>=) 3. * Pregnancy or lactation * Known alcohol or drug abuse * History of uncontrolled intercurrent illness including hypertension, active infection, diabetes * Clinically significant (i.e., active) cardiovascular disease * All other significant diseases might impair the subject's tolerance of trial treatment * Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements * Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines * Legal incapacity or limited legal capacity * Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsistent with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization * Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call

Study Objectives This study will assess the prevalence of epidermal growth factor receptor (EGFR) mutations in newly diagnosed patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients with positive EGFR mutation results will enter an open-label, single arm study to evaluate progression-free survival and quality of life with first-line Tarceva (erlotinib) therapy. Patients will receive Tarceva at a dose of 150 mg orally daily. Anticipated time on study treatment is until progressive disease or unacceptable toxicity occurs. Patients with negative EGFR mutation results will be offered treatment as per the centre's standard of care. Conditions: Non-Squamous Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: erlotinib [Tarceva] 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: * Adult patients, >= 18 years of age * Locally advanced or metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC) * ECOG performance status 0-3 * Treatment phase: histologically confirmed EGFR exon 19 deletion or exon 21 mutation in the diagnostic phase of the study * Adequate haematological, liver and renal function * Female patients must be postmenopausal, surgically sterile, or agree to use a barrier method of contraception * Male patients must be surgically sterile or agree to use a barrier method of contraception Exclusion Criteria: * Previous treatment for NSCLC with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor) * Symptomatic cerebral metastases * Pregnant or lactating women * Any other concomitant anti-cancer therapy (until disease progression and discontinuation of Tarceva therapy)

Study Objectives Phase II study of up-front chemotherapy and neo-adjuvant shortcourse radiotherapy for resectable rectal carcinoma. Study Design: Phase II, open-label, single-arm, multi-centre study. STUDY PRODUCT,DOSE,ROUTE,REGIMEN AND DURATION OF ADMINISTRATION: 1. Neoadjuvant Treatment (pre-operative chemo-radiotherapy regimen): FOLFOX4\* 2 cycles (WK1+WK3) - Tomotherapy\*\* (WK5) - FOLFOX4\* 2 cycles (WK7+WK9) \* Oxaliplatin 85 mg/m2 iv: day 1 Levofolinate 100 mg/m2 iv: day 1-2 5-fluorouracil 400 mg/m2 iv in bolus and 600 mg/m2 iv infusion over 22h: day 1-2 Every cycle will last 2 weeks (approximately 48 hours of treatment infusion and 12 days of rest). \*\* 25 Gy in 5 consecutive fractions, one fraction per day in 5 days on CTV (Clinical Target Volume) at the isodose of the 95% of the total dose. The treatment plan will be elaborated at the work-station dedicated to the Helicoidal Tomotherapy. The treatment could be planned also with linear accelerator with IGRT-IMRT technique or VMAT technique. 2. Restaging (week 11) 3. Surgery (week 12-16) with Total Mesorectal Excision (TME) 4. End Of Treatment (week 16-32) 5. Adjuvant therapy (The maximum interval between surgery and start of adjuvant therapy should be 8 weeks): 6. FOLFOX4\* 8 cycles (every 2 weeks) Study Duration: about 5 years. Enrollment period: 36 months. Treatment period: about 8 months. Follow-up: 1 year. NUMBER OF SUBJECTs: · Step A: a maximum of 6 patients. 6 evaluable patients are needed to assess toxicity. If 1 toxicity resulting in discontinuation of treatment will be observed in 6 patients, the treatment can be considered safe (with a confidence \> 90%). If 2 or more toxicity resulting in discontinuation of treatment on 6 patients, the study will be stopped because not safe and another type of radiotherapy schedule must be designed. · Step B: a total of 50 patients is required to be recruited in 2 years (including patients enrolled in Step A). The goal is to achieve a proportion of at least 15% of patients with a complete pathological response with the new radiochemotherapeutic treatment. Conditions: Rectal Carcinoma Intervention / Treatment: DRUG: FOLFOX4, RADIATION: Tomotherapy, PROCEDURE: TME (Total Mesorectal Excision) Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologically or cytologically confirmed diagnosis of adenocarcinoma of the mid-low rectum (within 12 cm from the anal verge) * Stage: lowT2N0, T2N+M0, T3-4 N-/+M0 (N+ = >= 3 nodes >0,5 cm diameter or >= 1 nodes > 1 cm diameter) * Age >=18 and <= 80 years * ECOG performance status 0-1 * Patients must have normal organ and marrow function as defined below: 1. - Leukocytes >= 3,000/mL 2. - Absolute neutrophil count >= 1,500/mL 3. - Platelets >= 100,000/mL 4. - Total bilirubin <= 1.5 X ULN 5. - AST (SGOT)/ALT (SGPT) <= 2.5 X ULN 6. - Creatinine <= 1.5 X ULN * Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter * Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: * Metastatic disease * Patients who have had any chemotherapy or radiotherapy prior to entering the study * Acute or sub-acute gastrointestinal occlusion * Participation in another clinical trial, with any investigational agent within 30 days prior the study screening * Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma, superficial bladder tumor and in situ carcinoma of the uterine cervix) * History of allergic reactions attributed to compounds of similar chemical or biological composition to drugs used in the study * Uncontrolled concomitant illness, including but not limited to: ongoing or active infections; congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance to study requirements

Study Objectives To compare the safety, tolerance and efficacy of fluconazole and amphotericin B as treatment for biopsy proven fungal infections in major organs, disseminated infection, suspected fungal infection and fungemia in adult neutropenic and non-neutropenic patients without AIDS, AIDS related complex (ARC), or extensive burns. HIV seropositive patients are allowed only if they also have a malignancy. Conditions: Mycoses, HIV Infections Intervention / Treatment: DRUG: Fluconazole, DRUG: Amphotericin B Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT

Inclusion Criteria Concurrent Medication: Allowed: * Immunostimulants under studies carried out under an IRB approved protocol. * Treatments of intercurrent non-fungal infection. * Allowed but requires monitoring during fluconazole therapy: * Barbiturates. * Phenytoin. * Oral hypoglycemics. * Coumarin-type anticoagulants. Patients must have the following: * Diagnosis or presumption of fungal infection under defined conditions. * Written informed consent either from the patient or the patient's legal guardian. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: * Burns > 30 percent of the body. * Diagnosis of AIDS or AIDS related complex (ARC). * HIV positive unless they have a malignancy. * History of allergy to or intolerance of imidazoles or azoles. * Moderate to severe liver disease as defined by specific lab values. * Unlikely to survive more than 24 hours. * Evidence of previous amphotericin B sensitivity. Concurrent Medication: Excluded: * Concomitant antifungal agents other than the study drugs. * Immunostimulants, except for studies carried out under an IRB approved protocol. Concurrent Treatment: Excluded: * Lymphocyte replacements. Patients with the following are excluded: * Defined disease conditions listed in Exclusion Co-Existing Conditions. * Unlikely to survive more than 24 hours. * Previous participation in this study; reentry for the same infection is not allowed. * Known to be unable to take amphotericin B due to acute toxicities. Prior Medication: Excluded: * Previous fluconazole therapy for this infection.

Study Objectives The purpose of this study is to see how well patients tolerate the side effects of treatment with Floxuridine, Oxaliplatin and Irinotecan. We also want to know if these methods used together are a useful way of treating cancer. We have studied these drugs and know the best doses of each when they are used alone. We do not yet know how well the drugs work with each other. This study will tell us the best doses of each drug when they are given over the same period of time. Conditions: Colon Cancer, Rectal Cancer Intervention / Treatment: DRUG: Floxuridine, Oxaliplatin, CPT-11, DRUG: Floxuridine, Oxaliplatin, CPT-11 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: * History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Confirmation of diagnosis must be performed at MSKCC. * Patient's liver metastases must be deemed unresectable and comprise <70% of the liver parenchyma. * A patient may have had prior chemotherapy or be previously untreated. * Patient may not have received prior treatment with FUDR or >2 doses of Oxaliplatin. * KPS > or = to 60%. * WBC > or = to 3,000 cells/mm3 and platelet count > or = to 100,000 cells/mm3 within 14 days of registration. * Creatinine < or = to 1.5 mg/dl within 14 days of registration. * Total serum bilirubin < or = 2.0 mg/dl within 14 days of registration. Exclusion Criteria: * No active concurrent malignancies: except a patient's potentially resectable colorectal primary. * Patient must not have obstruction of GI or GU tract. * Patient must not have current, symptomatic peripheral sensory neuropathy. * No prior radiation to liver. * No active infection, ascites, or hepatic encephalopathy. * Age >= 18 years. * Female patients cannot be pregnant or lactating. * Signed informed consent.

Study Objectives Patients at risk for having prostate cancer usually undergo a biopsy of their prostate. This is most often done in the private urology office. Recent studies have suggested that injection of local anesthesia (lidocaine) near the nerves of the prostate will improve pain sensation during the biopsy procedure. Local anesthesia can be given through a separate needle through the rectal probe just prior to biopsy. However, many urologists to date perform their biopsies without anesthesia. Some claim that the needle used for anesthesia causes pain itself. Others claim that the pain is so minimal that the additional use of lidocaine (and extra time) is not necessary. We plan to reexamine the use of lidocaine and perform the first study where each patient will receive lidocaine and placebo on separate sides of their prostate. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Lidocaine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients who are undergoing prostate ultrasound-guided biopsy from the practice of Drs. Diokno and Hollander. * Patients must speak English. * Patients must sign consent form. Exclusion Criteria: * Patients having received prior radiation to the pelvic area. * Patients with any neurologic disorder that may interfere with pain sensation during biopsy. * Allergy to Lidocaine * Patients requiring additional anesthesia (e.g. anxiolytics)

Study Objectives This phase II study is evaluating the activity of Pemetrexed in patients diagnosed with low risk Gestational Trophoblastic Tumor (GTT) that have failed prior treatment. Conditions: Trophoblastic Neoplasms, Uterine Neoplasms, Hydatidiform Mole, Choriocarcinoma Intervention / Treatment: DRUG: Pemetrexed 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: * Persistent or recurrent low risk Gestational Trophoblastic Tumor (GTT) * WHO score 2-6 (re-evaluated at the time of relapse * Histologically confirmed complete or partial moles on initial evacuation * Patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day of, and 2 days following administration of pemetrexed. * All patients taking NSAIDs with longer half-lives, should interrupt dosing for at least 5 days before, the day of, and 2 days following pemetrexed administration. * Folic Acid (350-1000 micrograms) must be given daily beginning approximately 5-7 days prior to first dose of pemetrexed and continuing daily until 3 weeks after the last dose of study therapy. * Vitamin B12 (1000 micrograms) will be administered as an intramuscular injection approximately 1 to 2 weeks prior to first dose of pemetrexed and repeated approximately every 9 weeks until 3 weeks after the last dose of study therapy. Exclusion Criteria: * Previous treatment that included chemotherapy other than actinomycin -D or methotrexate (+/- folinic acid). * Patients with more than 8 metastatic lesions identified * Patients with metastases to liver, spleen, brain, kidney or GI tract

Study Objectives The objective of this Phase I/II pilot study is to evaluate the safety and effectiveness of a non- antibiotic chelator based lock solution that contains nitroglycerin in combination with sodium citrate and ethanol (NiCE lock solution) for prevention of central line associated bloodstream infection (CLABSI). * The primary objective of this study is to evaluate the safety and estimate the rate of adverse events associated with the NiCE lock solution. * The second primary objective is to estimate the rate of CLABSI in patients receiving the NiCE lock solution. Conditions: Catheter-Associated Infections, Catheter-Related Infections Intervention / Treatment: DRUG: Nitroglycerin-citrate-ethanol (NiCE) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Inpatients who have a long term central venous catheter (CVC)-and the CVC has been in place for at least 14 days and is expected to remain in place at least for 30 days after enrollment * The CVC consists of a 5.0 French size, dual-lumen, peripherally inserted central catheter * Patients who are willing and capable to provide Informed Consent * Patients who are willing and capable to follow the instructions required to complete the study * Females (of child bearing potential) and males (of child bearing potential) must be abstinent or agree to use birth control during the study. Exclusion Criteria: * Patients who have an antimicrobial CVC. * Patients who have a short term CVC that have been placed in ICU (mainly rigid wall CVCs placed for acute care in ICU). * Patients who are hypotensive with a systolic blood pressure reading of <110 mmHg at any time over the 3 days prior to study entry * Patients who are not awake, not alert, or who cannot express pain or discomfort related to the catheter locks * Patients with an existing local or systemic infection as defined by evidence of fever (a body temperature > 38.0o C with two readings taken at least 10 minutes apart or one body temperature > 38.3o) and any of the following within 24 hours of enrollment: Pulse rate > 100 beats/min.; Respiratory rate > 20/min.; WBC count >12,000/mm3, <4,000/mm3 or differential count showing >10% band forms. Patient will still be eligible for the study if the participant's white blood cell count (WBC) is outside normal limits due to chemotherapy treatment or underlying conditions. Systolic blood pressure <90 mm Hg. * Signs and symptoms of localized catheter-related infection (tenderness and/or pain, erythema, swelling, purulent exudates within 2 cm of entry site) * Patients with an occluded (partially or totally) catheter defined as inability to either withdraw blood or instill 3cc of fluid without resistance through any catheter lumen * Patients with multiple co-existing central venous catheters at the time of enrollment will not be enrolled. * Patients in whom the lock solution application will interfere with routine treatment of the underlying disease * Patients with a known history of allergic reaction to ethanol, nitroglycerin, or citrate. * Female patients who are pregnant or breast feeding * Patients who are on disulfiram, metronidazole or are dependent on alcohol * Patients receiving phosphodiesterase type 5 (PDE-5) inhibitors (such as sildenafil, tadalafil, vardenafil).

Study Objectives RATIONALE: Monoclonal antibodies, such as cetuximab, 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. PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with recurrent or stage IIIB or stage IV lung cancer. Conditions: Lung Cancer Intervention / Treatment: BIOLOGICAL: cetuximab 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 bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features meeting 1 of the following stage criteria: * Stage IIIB disease (with pleural or pericardial effusion) * Stage IV disease * Recurrent disease * Measurable disease * Tumor tissue available from biopsy * Age of 18 and over * ECOG performance status of 0-2 * Life expectancy greater than 3 months * White blood cell (WBC) >= 3,000/mm^3 * Absolute neutrophil count >= 1,500/mm^3 * Platelet count >= 100,000/mm^3 * Bilirubin normal * Aspartate aminotransferase (AST) and/or alanine aminotranferease (ALT) <= 2.5 times upper limit of normal * Creatinine normal OR Creatinine clearance >= 60 mL/min * No more than 1 prior chemotherapy regimen for advanced BAC * More than 3 years since prior chemotherapy for other malignancies * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for this malignancy and recovered * HIV-positive patients are eligible provided the following criteria are met: * CD4 count >= 100/mm^3 * Undetectable viral load within the past 3 months * Receiving a stable antiretroviral regimen for >= 4 weeks before study entry * Fertile patients must use effective contraception * At least 2 weeks since prior radiotherapy and recovered EXCLUSION CRITERIA: * Untreated brain metastases * Patients with stable brain metastases >= 4 weeks after external beam radiotherapy to the brain are eligible * Acute hepatitis * Symptomatic congestive heart failure * Uncontrolled hypertension * Unstable angina pectoris * Cardiac arrhythmia * Pregnant or nursing * Prior allergic reaction to chimerized or murine monoclonal antibody therapy * Documented presence of human anti-mouse antibodies * Ongoing or active infection * Psychiatric illness or social situation that would preclude study compliance * Other uncontrolled illness * Prior cetuximab * Concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) * Other prior known epidermal growth factor receptor inhibitors (e.g., gefitinib or erlotinib) * Other concurrent investigational agents * Other concurrent anticancer therapy

Study Objectives The overall aim of this study is to evaluate two different central venous lines, PICC-lines (PICC) and subcutaneous venous access ports (SVAP) used for chemotherapy in women with breast cancer. The study will compare complications, material wear of the catheters used, patients'- and health care professionals' experiences, and costs. The study will give knowledge about which central venous access that is the most advantageous regarding adjuvant chemotherapy for women with breast cancer in the aspects of safety, quality of care, and quality of life. Conditions: Catheter Related Complications Intervention / Treatment: DRUG: FEC75 (or EC90) x 6, DRUG: FEC100 + Taxotere (EC90 + Taxotere) 3+3, DRUG: Paclitaxel Location: Sweden Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: BASIC_SCIENCE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * adjuvant or neo adjuvant chemotherapy, * speak Swedish Exclusion Criteria: * cognitive dysfunction * and/or inability to understand Swedish, * recurrent breast cancer

Study Objectives The main purpose of this study is to evaluate safety and effectiveness of the treatment of multiple myeloma with bortezomib in daily practice in the Netherlands. Conditions: Multiple Myeloma, Hematological Neoplasms Intervention / Treatment: DRUG: bortezomib Location: Netherlands Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients have to sign a statement that they agree with collection of their clinical data for this project * the patient is eligible, in the investigator's opinion, based on the criteria in the summary of product characteristics for bortezomib Exclusion Criteria: * If patients meet the eligibility criteria, there are no exclusion criteria.

Study Objectives This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and adding trastuzumab at the time of disease progression may be an effective treatment for breast cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: Everolimus, BIOLOGICAL: Trastuzumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Patients will be included in the study based on the following criteria: * Hormone-refractory metastatic breast cancer defined as disease progression within 6 months from starting most recent hormonal therapy * At least one line of endocrine therapy in the metastatic setting * Candidate for hormonal therapy (ER and/or progestin receptor [PR]-positive at primary diagnosis and at metastatic diagnosis where tissue is available) * HER2/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]-negative if IHC 3+) at primary diagnosis * Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC * If biopsy of metastatic lesion is performed prior to study entry, HER2 expression by IHC must be 1+ or 2+ * Histologically confirmed, measurable or evaluable disease; if disease is measurable, Response Evaluation Criteria In Solid Tumors (RECIST) criteria should be used * Life expectancy > 6 months * Eastern Cooperative Oncology Group (ECOG) performance status <= 2 * Adequate bone marrow function as indicated by the following: * Absolute neutrophil count (ANC) > 1500/µL * Platelets >= 100,000/µL * Hemoglobin > 10 g/dL * Adequate renal function, as indicated by creatinine <= 1.5x upper limit of normal (ULN) * Adequate liver function, as indicated by bilirubin <= 1.5x ULN * International normalized ratio (INR) <= 1.3 (or <= 3 on anticoagulants) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x ULN unless related to primary disease * Signed informed consent * Adequate birth control * Fasting serum cholesterol <= 300 mg/dL OR <= 7.75 mmol/L AND fasting triglycerides <= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. Exclusion Criteria: Patients will be excluded from the study based on the following criteria: * Prior treatment with trastuzumab or other HER2-directed therapies or with an mammalian target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory) * HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed) * Active infection * Uncontrolled central nervous system metastases * Life-threatening, visceral metastases * Pregnant or lactating women * Prior chemotherapy within the last 4 weeks * Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation) * Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias * Ejection fraction < 50% or below the lower limit of the institutional normal range, whichever is lower * Hypersensitivity to trial medications * Emotional limitations * Prior treatment with any investigational drug within the preceding 4 weeks * Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent * Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis * A known history of HIV seropositivity * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) * Patients with an active, bleeding diathesis * Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus) * Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus) * Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest * Taking any of the following agents: * Chronic treatment with systemic steroids or another immunosuppressive agent * Live vaccines * Drugs or substances known to be inhibitors or inducers of the isoenzyme cytochrome P450, family 3, subfamily A (CYP3A)

Study Objectives The primary objective of this study is to determine the progression-free survival (PFS) of participants with previously untreated metastatic malignant melanoma when treated with IMC-1121B (ramucirumab) alone or in combination with dacarbazine. Conditions: Metastatic Malignant Melanoma Intervention / Treatment: BIOLOGICAL: IMC-1121B (ramucirumab), DRUG: Dacarbazine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * The participant has histologically or cytologically confirmed melanoma that is stage IV (metastatic) * The participant has an Eastern Cooperative Oncology Performance Status (ECOG PS) of 0-1 * The participant has completed any prior radiotherapy, biologic/immunotherapy or vaccine therapy (for adjuvant or advanced disease) at least six weeks prior to the first dose of study therapy * The participant has adequate hematological functions [absolute neutrophil count (ANC) >= 1500 cells/microliter (μL), hemoglobin >= 9 grams/deciliter (g/dL) and platelets >= 100,000 cells/μL]. * The participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and/or alanine transaminase (ALT) <= 2.5 times the upper limit of normal (ULN), or <= 5.0 times the ULN if the transaminase elevation is due to liver metastases] * The participant has serum creatinine <= 1.5 x ULN [or a calculated creatinine clearance > 60 milliliters/minute (mL/min)] * The participant's urinary protein <= 1+ on dipstick or routine urinalysis [(UA); if urine dipstick or routine analysis is >= 2+, a 24-hour urine for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study] * The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) <= 1.5 and a partial thromboplastin time (PTT) <= 1.5 X ULN Exclusion Criteria * The participant has mucosal or intra-ocular melanoma * The participant has known or suspected brain or leptomeningeal metastases * The participant has had prior cytotoxic chemotherapy for metastatic malignant melanoma * The participant has had more than one line of biologic, immunologic or vaccine-based therapy for metastatic malignant melanoma (including therapy for adjuvant or advanced disease) * The participant has a nonhealing wound or ulcer * The participant has a known alcohol or drug dependency * The participant is pregnant or breastfeeding * The participant has a coexisting medical or psychiatric problem of sufficient severity to limit compliance with the study and/or increase the risks associated with study participation or study drug administration or interfere with the interpretation of study results * The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator

Study Objectives A study to evaluate the response of growth factor signatures (GFS) to a single dose of dalotuzumab in participants with triple negative (TN) or estrogen receptor (ER)-positive luminal B breast cancer. The primary hypothesis is that dalotuzumab will induce a decrease in the GFS in at least 40% of participants. Conditions: Breast Cancer Intervention / Treatment: DRUG: dalotuzumab (MK0646) Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participant has operable stage I-IIIa breast cancer of the following subtypes: (1) estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer; (2) ER-positive tumor meeting one of the following criteria: histologic grade 3; histologic grade 2 and PR-negative; histologic grade 2 and Ki67 antigen >=10%. Tumor is at least 2 cm in diameter as assessed by physical or radiographic exam * Participant is female and >=18 years of age Exclusion Criteria: * Participant is pregnant, breastfeeding or planning to become pregnant while in the study * Participant has received prior chemotherapy, biological therapy or radiation * Participant has participated in a clinical trial in the last 30 days * Participant has a history of drug or alcohol abuse in the last year * Participant is human immunodeficiency virus (HIV) positive. Patient has a history of Hepatitis B or C * Participant has poorly controlled diabetes mellitus