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Study Objectives Single centre prospective cohort phase III study of 18F-DOPA PET/CT imaging in specific patient populations: 1. Pediatric patients with congenital hyperinsulinism 2. Pediatric patients with neuroblastoma 3. Pediatric or Adult patients with suspected extra-pancreatic neuroendocrine tumor 4. Adult patients with a clinical suspicion of Parkinson's disease 5. Pediatric or Adult patients with primary brain tumors This study will evaluate the biodistribution and safety of 18F-DOPA produced at the Edmonton PET Centre. Conditions: Congenital Hyperinsulinism, Neuroblastoma, Neuroendocrine Tumors, Parkinson Disease, Brain Glioma Intervention / Treatment: DRUG: 18F-DOPA Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * 1. Pediatric patients (less than 17 years old) with congenital hyperinsulinism * 2. Pediatric patients (less than 17 years old) with neuroblastoma * 3. Pediatric patients (less than 17 years old) or Adult patients (17 or older) with known or clinically suspected neuroendocrine tumor outside of the pancreas * 4. Adult patients (17 or older) with a clinical suspicion of Parkinson's disease. * 5. Pediatric (less than 17 years old) or Adult patients (17 or older) with primary brain tumors Exclusion Criteria: * Unable to obtain consent * Weight > 250 kg (weight limitation of PET/CT scanner) * Adult patients unable to lie flat for 20-30 minutes to complete the PET/CT scan * Young pediatric patients (less than 10 years old) who are unable to lie flat for 20-30 minutes and for whom clinical sedation is contraindicated (as determined by a pediatric anaesthesiologist) * Pregnancy * Lack of intravenous access

Study Objectives Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estradiol can cause the growth of breast cancer. Hormone therapy using anastrozole may fight breast cancer by blocking the use of estradiol by the tumor cells. Sometimes when hormone therapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to hormone therapy. Giving sorafenib together with anastrozole may reduce drug resistance and allow the tumor cells to be killed. This phase I/II trial is studying the side effects and best dose of sorafenib when given in combination with anastrozole and to see how well they work in treating postmenopausal women with metastatic breast cancer. Conditions: Recurrent Breast Cancer, Stage IV Breast Cancer Intervention / Treatment: DRUG: sorafenib tosylate, DRUG: anastrozole 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: * Histologically or cytologically confirmed breast cancer * Metastatic disease * Measurable disease, defined as >=1 unidimensionally measurable lesion, including >= 1 of the following: * Lesion >= 10 mm on CT scan (5 mm sections) * Lesion >= 20 mm on CT scan or MRI (10 mm sections) * Bone disease that is >= 10 mm on MRI * Lytic bone lesions that are >= 10 mm on CT scan (with 5 mm sections) OR >= 20 mm on plain film or CT scan (with 10 mm sections) * Lesion >= 10 mm on physical exam * Patients must have received >= 1 prior aromatase inhibitor in either the adjuvant or metastatic setting and must have had either disease recurrence or disease progression on a prior aromatase inhibitor therapy * No brain metastases diagnosed within the past 6 months OR previously untreated brain metastases * Estrogen receptor-positive and/or progesterone receptor-positive, defined as > 1% staining by immunohistochemistry or > 10 fmol/mg of protein by radio-ligand dextran-coated steroid binding assay * Postmenopausal, as defined by 1 of the following: * Prior bilateral oophorectomy * No menses for >= 12 months in patients with an intact uterus * Follicle-stimulating hormone (FSH) in postmenopausal range in patients < 60 years of age who have had a prior hysterectomy or have been amenorrheic for >= 3 months * Age >= 60 years * Pre- or perimenopausal patients receiving monthly injections of goserelin at a dose of 3.6 mg are eligible * ECOG 0-2 * More than 3 months * Absolute neutrophil count >= 1,500/mm3 Platelet count >= 100,000/mm3 No bleeding diathesis * Bilirubin =< 1.5 times upper limit of normal (ULN AST and ALT =< 2.5 times ULN * Systolic blood pressure (BP) < 150 mm Hg and diastolic BP < 100 mm Hg on at least one reading prior to study entry No uncontrolled hypertension * None of the following within the past 6 months: * Symptomatic congestive heart failure * Unstable angina pectoris * Myocardial infarction * Cardiac arrhythmia with hemodynamic compromise * Not pregnant or nursing * Able to swallow oral medication * No known HIV positivity * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * No other active invasive malignancy within the past 5 years except nonmelanoma skin cancer or treated carcinoma in situ of the cervix * No other uncontrolled illness * More than 4 weeks since prior chemotherapy * No more than 2 prior chemotherapy regimens for metastatic disease * At least 8 weeks since prior anastrozole therapy * Concurrent steroids allowed if dose is stable * More than 4 weeks since prior radiotherapy * More than 4 weeks since prior major surgery * Recovered from prior therapy * No prior sorafenib * No concurrent therapeutic anticoagulation * Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided PT and PTT are =< 1.5 times ULN * No concurrent agents that may interact with sorafenib, including any of the following: * Hypericum perforatum (St. John's wort) * Rifampin * P450 CYP3A4 enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, or phenobarbital) * No other concurrent investigational agents Exclusion Criteria: * estrogen receptor status unknown * history of myocardial infarction within 6 months * performance status 3 * performance status 4 * premenopausal * progesterone receptor status unknown * HIV positive

Study Objectives A Phase Ia/Ib Safety and Tolerability Evaluation of Low-dose Radiation in Combination with CS1001 in relapsed SCLC patients Conditions: Relapsed Small Cell Lung Cancer Intervention / Treatment: DRUG: CS1001 Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologically or cytologically confirmed LS-SCLC or ES-SCLC and experienced progression since first-line standard platinum containing dual-drug chemotherapy. * Patients whose initial diagnosis was limited must undergo radical chest radiotherapy and the time of tumor progression is not less than 3 months from the end of radiotherapy, or cannot receive radical chest radiotherapy due to specific reasons * At least one extracranial measurable lesion (RECIST v1.1), and for a lesion that has received radiotherapy, progression of the lesion after radiotherapy must be confirmed. * Patients with brain metastases are allowed to receive previous radiotherapy and their condition is stable, but the time to the end of radiotherapy must not be less than 3 months. * No radiotherapy contraindications were judged by the radiologist * ECOG performance status of 0 or 1. * Patients with life expectancy ≥ 3 months. * Patients must have adequate organ function. * Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 6 months after last study drug administration. Exclusion Criteria: * Subjects known to have primary CNS tumors or meningeal metastases or unstable CNS metastases. * Patients with active autoimmune diseases or history of autoimmune diseases should be excluded. * Patients who have received immune checkpoint proteins/antibody/medicine (including PD-1, PD-L1, etc) for treatment. * Known history of HIV infection. * Subjects with active chronic hepatitis B or active hepatitis C . * Patients who have serious hypersensitive reaction to monoclonal antibodies, and have history of uncontrolled allergic asthma. * Known history of alcoholism or drugs abuse. * Subjects with history of radiation pneumonitis of grade 3 or above, regardless of recovered or not.

Study Objectives Waldenström's Macroglobulinemia (lymphoplasmacytic lymphoma, WM) remains incurable with limited therapeutic options and notably absent FDA approved therapy with any WM indication. Therefore, there is a need to identify new therapeutic agents for WM patients both in the upfront and relapsed/refractory setting. The purpose of this research study is to assess the efficacy of perifosine in patients with relapsed or refractory WM. Conditions: Waldenstrom's Macroglobulinemia Intervention / Treatment: DRUG: Perifosine 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: * 18 years of age or older * Must have received prior therapy for their WM and have relapsed or refractory WM. Any number of prior therapies is acceptable * Measurable disease, defined as presence of immunoglobulin M paraprotein with a minimum IgM level of equal to or greater than 2 times the ULN and over 10% of lymphoplasmacytic cells in bone marrow * ECOG Performance Status 0,1, or 2 * Laboratory values as described in the protocol * Life expectancy of greater than 12 weeks Exclusion Criteria: * Uncontrolled infection * Other active malignancies * CNS involvement * Cytotoxic chemotherapy less than 3 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration. * Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational * Pregnant or nursing women * Known to be HIV positive * Radiation therapy less than 2 weeks prior to registration

Study Objectives The present study is a multicenter, prospective phase II-study investigating the combination of treosulfan, etoposide, and cyclophosphamide as conditioning regimen for patients with acute lymphoblastic leukemia who are not eligible for a TBI-containing regimen. Conditions: Acute Lymphoblastic Leukemia Intervention / Treatment: PROCEDURE: Hematopoietic stem cell transplantation Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Acute lymphoblastic leukemia in first or subsequent complete remission * Indication for allogeneic stem cell transplantation according to the actual protocol of the German Acute Lymphoblastic Leukemia Study Group * Patient's age: 18-65 years * HLA-identical or compatible related or unrelated donor (HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1) (one antigen-mismatch allowed) * Not eligible for total-body irradiation due to one of the following reasons: * prior radiation of the spine > 30 Gy * prior radiation of the mediastinum > 30 Gy * severe pulmonary infection during induction chemotherapy * DLCO > 50% * Patient's wishing to avoid total-body irradiation as conditioning regimen * Patient's written informed consent * Women and men capable of reproduction must agree to use highly effective methods of contraception until six months after treatment termination. For men: vasectomy, sexual abstinence, or partner is using hormonal IUD, implants, injectables, oral hormonal contraceptives or is surgically sterilized. For women: hormonal IUD, implants, injectables, sexual abstinence, surgical sterilization, vasectomised partner Exclusion Criteria: * No complete remission at time of registration * Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as * total bilirubin, SGPT or SGOT > 3 times upper the normal level * Left ventricular ejection fraction < 30% * Creatinine clearance < 30 ml/min * DLCO < 35% and/ or receiving supplementary continuous oxygen * Positive serology HIV * Pregnant or lactating women * Severe florid infection * Experienced hypersensitivity against cyclophosphamid, etoposide, or treosulfan * Cystitis * Obstructive renal function * Participation in any other clinical drug trial * Serious psychiatric or psychological disorders * Progressive invasive fungal infection at time of registration

Study Objectives The molecular mechanisms involved in squamous cell carcinoma of the anus (SCCA) are poorly elucidated. HIV-positive and renal transplant patients are at high risk for developing SCCA, indicating that immune suppression plays a facilitating role. The investigators previously demonstrated that chromosomal instability (CIN) was more prevalent in SCCA of HIV-negative than HIV-positive patients. Hence, the investigators postulate that microsatellite instability (MSI), another molecular pathway, might be a feature of SCCA progression in the HIV-positive population. Study Aims: 1. to determine the prevalence of MSI in paraffin-embedded tumor specimen of 15 patients from the Swiss HIV cohort who underwent surgical excision for SCCA; and 2. eventually, to test our hypothesis by assessing the MSI status of SCCA in 15 recently operated HIV-negative patients. Study Design: The study is designed in two steps: 1. Firstly, the investigators will retrieve tumor specimen from 15 HIV-positive patients, with a biopsy-confirmed diagnosis of SCCA, in three institutions. DNA from tumor and normal tissues will be extracted, and then amplified by PCR. Presence of MSI in tumors will be determined by assessing the microsatellite markers BAT25, BAT26, and CAT25. 2. Secondly, the results of molecular analysis will be compared with a population of HIV-negative patients, with the same tumors, using the same detection technique for MSI. Conditions: Carcinoma, HIV Infections Location: Switzerland Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Biopsy proven Squamous cell carcinoma of the anus * Informed consent Exclusion Criteria: * None

Study Objectives The purpose of this study is to evaluate the safety and tolerability as well as the pharmacodynamic effects of multiple doses of AVX-470 administered orally in patients with active ulcerative colitis. Conditions: Ulcerative Colitis Intervention / Treatment: DRUG: AVX 470, DRUG: Placebo Location: Canada, Belgium, United States, Hungary Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Men or women aged 18 75, inclusive * Established diagnosis of ulcerative colitis involving the sigmoid colon or proximal segments of bowel * Total Mayo score between 5-12, inclusive, with endoscopic subscore of the Mayo score ≥ 2 and > 15 cm of involvement beyond the anal verge Exclusion Criteria: * Women with a positive pregnancy test, who are breastfeeding, or who intend to become pregnant during the course of the study * Diagnosis of Crohn's disease, microscopic colitis or indeterminate colitis * Presence of ileostomy or colostomy, or history of prior colon resection * Patients with planned hospitalization or surgery during the course of the study * Known allergy to milk proteins, red meat or cornstarch * Stools positive for enteric infection, including parasitic, or C. difficile toxin within 28 days of screening * Documented presence of Hetatitis B (HBsAg), Hepatitis C (HCV), or HIV * Presence of dysplasia of any grade on colonoscopic biopsies * Treatment for cancer (excluding non-melanomatous cancer of the skin or cervical carcinoma in situ) or lymphoproliferative disorder (including lymphoma) within 5 years * History of tuberculosis (TB) or Listeria infection, or known exposure to another person with active TB disease within 12 weeks of screening; or history of past or current infection with different opportunistic infections * History of TNF inhibitor (infliximab, adalimumab or certolizumab pegol) use with primary treatment failure. Secondary treatment failures due to intolerance, allergic reaction, or loss of response will not constitute a basis for exclusion. Oral immunosuppressives, mesalamine, and corticosteroids (up to 20mg of prednisone per day) will be permitted so long as these medications are stable for defined periods of time before study participation commences.

Study Objectives The objective of this study is to establish the performance characteristics of an assay that detects the recurrence of bladder cancer in patients previously diagnosed with bladder cancer. The study is conducted at locations within and outside of the United States. Testing is performed on urine specimens provided by eligible enrolled patients. Results from this study will not be used for patient management decisions. Conditions: Bladder Cancer Intervention / Treatment: DEVICE: Xpert Bladder Cancer Monitor Location: Canada, Netherlands, United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Subject is ≥ 40 years of age * Subject has provided documented informed consent as required by the reviewing IRB or EC. Experimental Bill of Rights will be documented for all subjects enrolled in applicable states. * Subject is considered disease positive within 12 months (365 days) of enrollment. * At the time of the enrollment visit, the subject is scheduled for a standard of care cystoscopy which will be completed within 3 days of providing a urine specimen. * Subject has agreed to provide at least 60 mL of voided urine for study purposes at the enrollment visit. * Subject has agreed to provide at least 60 mL of voided urine for study purposes at each subsequent standard of care cystoscopy visit for at least 12 months (365 days) following enrollment if the subject will enter the Longitudinal cohort. * Any subject considered anticipatory positive at the initial visit shall be enrolled into the longitudinal cohort. For each anticipatory positive enrolled into the longitudinal cohort a random disease negative subject shall be enrolled. Exclusion * Subject has been previously enrolled into the study. * Urine specimen to be used for study purposes is from the first morning void. * Subject has had an excision procedure within six weeks (42 days) of enrollment. * The subject is not scheduled for a standard of care cystoscopy visit within 12 months (365 days) following enrollment.

Study Objectives This is a phase 3, multi-center, single dose, open-label, exploratory study in suspected lung cancer patients scheduled to undergo endoscopic or thoracic surgery per CT/PET/MRI or other imaging based on standard of care. This study aims to assess the efficacy of OTL38 and Near Infrared Imaging (NIR) at identifying pulmonary nodules within the operating theater, and to assess the safety and tolerability of single intravenous doses of OTL38. Conditions: Lung Neoplasms, Lung Cancer Intervention / Treatment: DRUG: OTL38 for Injection, DEVICE: Near infrared camera imaging system Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: DIAGNOSTIC Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male and Female subjects 18 years of age and older * Have a primary diagnosis, or a high clinical suspicion, of cancer in the lung warranting surgery based on CT/PET or other imaging * Are scheduled to undergo surgical thoracoscopy for diagnostic wedge resection followed by anatomic lung resection * Female subjects of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion * Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments Exclusion Criteria: * Previous exposure to OTL38 * Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the subject * History of anaphylactic reactions to folate, including synthetic folic acid (pteroylmonoglutamic acid) and contrast agents containing indocyanine green for near infrared imaging. Subjects with a medical history of 'idiopathic anaphylaxis' will require evaluation. * History of allergy to any of the components of OTL38, including folic acid * A positive serum pregnancy test at Screening or a positive urine pregnancy test on the day of surgery or day of admission for female subjects of childbearing potential * Clinically significant abnormalities on electrocardiogram (ECG) at screening. * Presence of any psychological, familial, sociological condition or geographical challenges potentially hampering compliance with the study protocol and follow-up schedule * Impaired renal function defined as eGFR< 50 mL/min/1.73m2 * Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >2x ULN for total bilirubin except in subjects with Gilbert's syndrome. * Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to the administration of study drug * Known sensitivity to fluorescent light

Study Objectives The purpose of this study is to evaluate the safety of the study drug known as LY3321367, an anti-T-cell immunoglobulin and mucin-domain domain-containing molecule-3 (TIM-3) antibody administered alone or in combination with LY3300054, an anti-programmed death ligand 1 (PD-L1) antibody, in participants with advanced relapsed/refractory solid tumors. Conditions: Solid Tumor Intervention / Treatment: DRUG: LY3321367, DRUG: LY3300054 Location: Spain, Japan, United States, Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * For Ph1a monotherapy and combination cohorts, histologic or cytologic confirmation of advanced solid tumor. * For Phase 1a and 1b, prior PD-1 or PD-L1 therapy or other immunotherapy is allowed, if the following criteria are met: * Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. * Must have completely recovered or recovered to baseline prior to screening from any prior AEs occurring while receiving prior immunotherapy. * Must have provided tumor tissue sample, as follows: * For participants entering Ph1a: have submitted, if available, an archival tumor tissue sample. * For participants entering Ph1b: have submitted, a sample from a newly obtained core or excisional biopsy of a tumor lesion or a recent biopsy defined by 6 months of study enrollment (Ph1b). * Must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Must have adequate organ function. * Have an estimated life expectancy of 12 weeks, in judgement of the investigator. Exclusion Criteria: * Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids (participants receiving anticonvulsants are eligible). * Have received a live vaccine within 30 days before the first dose of study treatment. * If female, is pregnant, breastfeeding, or planning to become pregnant. * Have a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's participation. * Have moderate or severe cardiovascular disease. * Have a serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including active or chronic infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment. * Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, cyclosporine). \[Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted\]. * Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection. * Evidence of interstitial lung disease or noninfectious pneumonitis.

Study Objectives When the DNA inside of human cells undergoes certain alterations (mutations), the cells may develop into a cancer. The cancer cells may shed this DNA into the blood stream. This circulating tumor DNA (ctDNA) can be detected by very sensitive, specialized laboratory tests. Measurement of ctDNA has been shown to be useful for following patients with known cancer. It has also been found in the circulation of some patients with early stage cancer. The purpose of this study is to examine blood specimens for the presence of ctDNA in individuals without known cancer who are scheduled to undergo a screening or diagnostic colonoscopy in order to see if the ctDNA test can detect a cancer or precancerous condition at a very early stage before the patient becomes symptomatic. The results of this study should help define the role of ctDNA in the detection of early stage colon cancer and to define how sensitive it is (i.e. how well it picks up cancer when it is present) and how specific it is (i.e. how often is ctDNA found in patients with benign diseases or no abnormalities). Conditions: Colon Cancer, Colon Adenomas, Colon Polyps Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: . * 18 years of age or older who are scheduled to undergo a screening or diagnostic colonoscopy by Dr. Phillip Fleshner Exclusion Criteria: * Prior history of cancer excluding basal cell carcinoma of the skin

Study Objectives Screening programs and advances in imaging have led to more breast lesions being diagnosed at an impalpable stage. Multiple localisation techniques for nonpalpable breast lesions have been developed during the past decades. Specifically, several alternatives to the golden standard hooked-wire technique have become available, of which magnetic seed localisation is one of the newest approaches. Since September 2018, Magseed® localisation is the standard of care for localising impalpable breast lesions in UZ Leuven. In this study, the oncological safety, the clinical safety and surgeon satisfaction of Magseed® localisation will be assessed and retrospectively compared to hooked-wire localisation. Conditions: Oncology, Breast Cancer Intervention / Treatment: DEVICE: Preoperative localisation technique Location: Belgium Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Breast conserving surgery with preoperative localisation * Minimum 18 years old

Study Objectives This is a two part phase I study in Japanese patients that will determine the safety, tolerability and pharmacokinetics of pazopanib monotherapy and of pazopanib in combination with lapatinib. Conditions: Carcinoma, Renal Cell Intervention / Treatment: DRUG: pazopanib, DRUG: Lapatinib Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Signed informed consent. * Histologically or cytologically confirmed diagnosis of advanced solid tumor. * Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study. * ECOG performance status of 0 or 1. * Adequate bone marrow reserve and hepato-renal function. * Able to swallow and retain oral medication. * For combo part, left ventricular ejection fraction within normal range or above 50%. Exclusion criteria: * Prior treatment with pazopanib, and with lapatinib for combo part. * Clinically significant gastrointestinal abnormalities. * Sevier diseases or conditions other than cancer. * Poorly controlled hypertension. * Use of warfarin for therapeutic anticoagulation. * Use of other anti-angiogenesis agents, and other ErbB inhibitors for combo part. * Unresolved and/or unstable toxicities * Pregnant or lactating females

Study Objectives * The recently introduced chemoembolization has been considered to be a very attractive new method in terms of response in the treatment of liver metastases from colon cancer carcinoma (LM-CRC). It appears to be particularly useful if carried out with the new embolization materials. * An 80% response rate was reported using TACE with Irinotecan pre-loaded Beads in patients with liver metastases from colon cancer, who had been pretreated with 2 or more lines of chemotherapy. * Since a greater activity was attained by a combination of Cetuximab and Irinotecan versus Cetuximab in monotherapy, the European Agency for the Evaluation of Medicinal Products (EMEA) has granted authorization to the use of Cetuximab in association with irinotecan in the treatment of irinotecan-refractory CRC-LM. * In this study we want to collect data on on time to progression and tolerability using DEBIRI+Cetuximab in LM-CRC Conditions: Colon Cancer Liver Metastasis Location: Italy Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Unresectable hepatic metastases from colorectal carcinoma (CRC-LM) * Progression of disease after first line therapy containing Irinotecan completed at least one month previously * Performance status (PS) 0-2 * Biochemistry parameters within normal limits (ALT and gamma glutamyl transpeptidase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/ml) * Adequate information and subsequent written informed consent * Life expectancy > 3 months * Patients K-RAS wild type Exclusion Criteria: * Extension of disease greater than 50% of the parenchymal liver (confirmed by CAT scan or MRI) * Brain metastases * Severe and confirmed vascular diseases * Other concomitant malignancies except for cutaneous basal cell carcinoma or carcinoma in situ of the uterine cervix * Evidence of significant diseases such as uncontrolled diabetes, congestive heart failure, chronic renal insufficiency (CRI) * Known hypersensitivity reactions towards components of the study drugs * Pregnant or breastfeeding women or women of childbearing potential not making use of effective contraceptives * Family, psychological, social or geographical circumstances preventing the patient from undergoing follow-up and from complying with protocol procedures * Patients K-RAS mutant

Study Objectives Central South University in collaboration with Tianjin University developed the first domestically produced Chinese minimally invasive surgical (MIS) robot system which named "Micro Hand S" in 2013. This new MIS robot had been authorized to enter the clinical trial stage by the Ethics Committee of the Third Xiangya Hospital at Central South University. The Micro Hand S robot is safe and feasible in the preliminary study. However, compared with minimally invasive approaches (da Vici, laparoscope), the merits and demrits of rectectomy for rectal cancer are unclear. Therefore, the investigators conduct this retrospective study to focus on this concern. Conditions: Rectal Cancer Intervention / Treatment: DEVICE: Micro Hand S robot, DEVICE: Laparoscope Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * histologically confirmed rectal cancer; ASA score < 3 Exclusion Criteria: * palliative resections, combined resections, distant metastasis, a previous history of abdominal/or pelvic surgery

Study Objectives This phase I trial studies the side effects and best way of giving trastuzumab emtansine in treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that has spread to other parts of the body or nearby tissue and cannot be removed by surgery. Biological therapies, such as trastuzumab emtansine, may stimulate the immune system in different ways and stop cancer cells from growing. Conditions: HER2/Neu Positive, Recurrent Breast Carcinoma, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study, BIOLOGICAL: Trastuzumab Emtansine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed study-specific informed consent form * Histologically or cytologically documented breast cancer * Metastatic or unresectable locally advanced/recurrent breast cancer * HER2-positive disease documented as in situ hybridization (ISH)-positive and/or 3+ by immunohistochemistry (IHC) on previously collected tumor tissue * Absolute neutrophil count (ANC) > 1500 cells/mm\^3 * Platelet count > 100,000/mm\^3 * Hemoglobin > 9.0 g/dL (patients are allowed to receive transfused red blood cells \[RBC\] to achieve this level) * Total bilirubin =< 1.5 × upper limit of normal (ULN), except in patients with previously documented Gilbert's syndrome, in which case the direct bilirubin should be less than or equal to the ULN * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =< 2.5 × ULN * Alkaline phosphatase =< 2.5 × ULN (patients with hepatic and/or bone metastases: alkaline phosphatase =< 5 × ULN) * Serum creatinine < 1.5 × ULN * International normalized ratio (INR) < 1.5 × ULN * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Left ventricular ejection fraction (LVEF) >= 50% by either echocardiogram (ECHO) or multigated acquisition scan (MUGA) * Negative results of serum pregnancy test for premenopausal women of reproductive capacity and for women < 12 months after entering menopause * For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception; female patients of childbearing potential must agree to use two effective forms of non-hormonal contraception; effective methods of contraception include: intrauterine device (IUD); female condom; male condom; diaphragm with spermicide; cervical cap; or a sterile sexual partner; male patients with partners of childbearing potential must use barrier contraception; in addition, male patients should also have their partners use another method of contraception from the time of informed consent through the duration of study activity * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including thrombokinetic studies and platelet function studies Exclusion Criteria: CANCER-RELATED CRITERIA * Known platelet disorder, such as von Willebrand's disease or baseline platelet count of < 100,000/mm\^3 * Chemotherapy =< 21 days before first study treatment * Trastuzumab =< 21 days before first study treatment * Lapatinib =< 14 days before first study treatment * Investigational therapy or any other therapy =< 28 days before first study treatment * Any prior ado-trastuzumab emtansine * Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or metastatic breast cancer is not allowed if: * The last fraction of radiotherapy has been administered within 14 days of first on-study thormbokinetic study * The patient has not recovered from any resulting acute toxicity (to grade =< 1) prior to first on-study thormbokinetic study * Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within 14 days of first on-study thrombokinetic study; for patients with newly diagnosed brain metastases or unequivocal progression of brain metastases on screening scans, localized treatment (i.e., surgery, radiosurgery, and/or whole brain radiotherapy) is required before study enrollment; subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 14 days of stable neurologic function prior to the first thrombokinetic procedure; patients with small brain metastases not symptomatic and deemed requiring treatment by managing clinicians or study investigators may be permitted to enroll on study * History of intolerance (including grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins * Current peripheral neuropathy of grade >= 3 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0 * Current use of any platelet functioning inhibitors (including aspirin) within 14 days of first on-study thrombokinetic study CARDIOPULMONARY FUNCTION CRITERIA * Current unstable ventricular arrhythmia requiring treatment * History of symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] classes II-IV) * History of myocardial infarction or unstable angina within 6 months of enrollment * History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab treatment * Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy GENERAL CRITERIA * Current severe, uncontrolled non-cancer systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) resulting in a life expectancy of < 6 months * Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment * Current pregnancy or lactation * Current known active infection with human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C virus; for patients who are known carriers of hepatitis B virus (HBV), active hepatitis B infection must be ruled out based on negative serologic testing and/or determination of HBV deoxyribonucleic acid (DNA) viral load per local guidelines * Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Study Objectives The present study aims at studying how safe and tolerable a new therapy for patients with Acute Lymphoblastic Leukemia (ALL) is. This new therapy consists of an immunotherapy, that is an approach focusing on the immune system, and it targets ALL patients in complete remission but who may still have the disease at a cellular level (this is called 'minimal residual disease'). For any further information, please, discuss with your treating physician. Conditions: Acute Lymphoblastic Leukemia, Complete Hematologic Remission (CHR), Persistent/Recurrent Minimal Residual Disease (MRD) Intervention / Treatment: OTHER: Autologous NK cells infusions Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult subjects with Ph+ ALL in CHR (1st or 2nd) with MRD positivity confirmed at baseline, older or equal to 60 years or not eligible for other post-CHR treatment modalities. * WHO score 0-1. * Hematopoietic, liver and renal normal functions defined as follows: WBC bigger or equal to 2.000/mm3 lymphocytes bigger or equal to 500/mm3 neutrophils bigger or equal to 1.000/mm3 platelets bigger or equal to 50.000/mm3 Hb bigger or equal to 9 g/dl creatinine fewer or equal to 1.5 x ULN bilirubin fewer or equal to 1.5 x ULN AST and ALT less than 3 times the upper limit of normal. LDH less than 2 times the upper limit of normal. * For male and female subjects of childbearing potential, agreement to use effective contraception. * Authorization by Istituto Superiore di Sanità (ISS) according to DM 2 March 2004. * Signed written informed consent according to ICH/EU/GCP and national local regulations. Exclusion Criteria: * Concurrent chemotherapy or immunotherapy (TKI maintenance is permitted). * Any contraindications to perform a leukapheretic procedure for mononuclear cell collection. * Active or chronic infection, including Treponema, HIV, HBV and/or HCV unless antigen/PCR negative. * Presence of autoimmune symptoms. * Pregnant or lactating females. * Simultaneous participation in another clinical trial. * Any physical or psychological impediment in a patient that could lead the investigator to suspect his/her poor compliance to the protocol.

Study Objectives the efficacy and safety ofhe use of regorafenib in combination with nivolumab Conditions: Advanced and Metastatic Solid Tumor Intervention / Treatment: DRUG: Regorafenib, DRUG: Nivolumab Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients who provided written informed consent to be subjects in this trial * Patients at least 20 years of age on the day of providing consent * Dose-escalation cohort: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors. Expansion cohort: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors (gastric, colorectal, or hepatocellular cancer). * Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Patients capable of taking oral medication * Patients with evaluable or measurable lesions as per RECIST version 1.1 * Patients with adequate organ function at the time of enrollment as defined below: * Neutrophil count ≥1500mm3 * Platelet count ≥10.0 × 104/mm3 * Hemoglobin (Hb) ≥ 9 g/dL, * aspartate transaminase (AST), alanine transaminase (ALT) ≤100 U/L (≤100 U/L in patients with Hepatocellular carcinoma, ≤250 U/L in patients with liver metastasis) * Total bilirubin ≤1.5-mg /dL * Creatinine ≤1.5--mg /dL * Lipase ≤ 80 IU/L * Urinary protein: It satisfies one of the following (if any of the inspection criteria are satisfied, other examination may not be carried out) (i) urinary protein (test paper method) is 2+ or less (ii) Urine Protein Creatinine(UPC) ratio <3.5 (iii) 24-hour urine protein was measured, urinary protein ≦ 3500 mg * Prothrombin time (PT)- International normalized ratio(INR): ≤ 1.5 (≦ 3.0 in case of anticoagulant administration) * For women who are likely to become pregnant (including those without menstruation due to medical reasons such as chemical menopause) Note 1, we agreed to double contraceptive Note 2 for at least 5 months from consent acquisition patient to the final administration of the investigational product. Also, patients who agreed not to breast feeding for at least 5 months from acquiring consent to the final investigational drug administration. For men, patients agreeing to double contraceptive for at least 7 months from the time of starting investigational drug administration to the final investigational drug administration. Note 1): A woman who is likely to become pregnant is a woman who has experienced menarche and is not undergoing sterilization surgery (such as hysterectomy, bilateral salpingo ligation or bilateral oophorectomy), a woman without menopause Everything is included. The definition after menopause shall be amenorrhea continuously for 12 months or more even though there is no noteworthy reason. Women who are using oral contraceptives or mechanical contraceptive methods (such as intrauterine contraceptive devices or barrier methods) are considered to be pregnant. Note 2): With regard to contraception, it is necessary to use two of the vasectomy or condom of a male patient or male male, the uterine tube ligation of a female patient or the other woman, a contraceptive pessary, an intrauterine contraceptive device or an oral contraceptive I need to agree to heavy contraception. Exclusion Criteria: * Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone therapy, or immunotherapy <2 weeks before enrollment. Immune checkpoint blockade as pretreatment is permitted. * Patients with a history of taking regorafenib. * Patients with hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents * Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment * Patients with a large amount of pleural effusion or ascites requiring drainage. * Patients with a ≥grade 3 active infection according to NCI-CTCAE version 4.03 * Patients with symptomatic brain metastasis * Patients with partial or complete gastrointestinal obstruction * Patients with interstitial lung disease with symptoms or signs of activity * Patients who test positive for either anti-HIV-1 antibodies, anti-HIV-2 antibodies, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies\* \*Patients who test positive for either anti-Hepatitis B surface(HBs) or anti- Hepatitis B core(HBc) antibodies, and those who have hepatitis B virus (HBV)-DNA measurements greater than the detection sensitivity will also be excluded. (However, patients with hepatocellular carcinoma in the expansion cohort will not be excluded even if they test positive for HBsAg and anti-HCV antibodies.) * Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease * Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy) or immunosuppressants, or who have received such a therapy <14 days before enrollment in the present study * Patients with a history or findings of ≥grade III congestive heart failure according to the New York Heart Association functional classification * Patients with a seizure disorder who require pharmacotherapy * Patients who had grade 3 or higher bleeding during 4 weeks before enrollment * Patients undergoing major surgery (thoracotomy or laparotomy, etc.), laparotomy biopsy, trauma within 28 days before registration. The same day of the week before 4 weeks can be registered (However, in case of an artificial anastomosis without intestinal resection, it shall be within 14 days before registration). * Patients with non-healing wound, non-healing ulcer, or non-healing bone fracture. * Patients with a history of hypersensitivity to any of the study drugs, similar drugs, or excipients. * Women who are pregnant or breastfeeding, or with the potential for pregnancy.

Study Objectives The purpose of this study is to determine the safety of regorafenib, an antiangiogenic drug, when combined with radioembolization using SIR-Spheres® microspheres in the treatment of colorectal cancer (CRC) that has spread to the liver. Conditions: Colorectal Neoplasms Intervention / Treatment: DEVICE: SIR-Spheres, DRUG: Regorafenib 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: * Histologically confirmed metastatic adenocarcinoma of the colon or rectum. * Patients who have been previously treated with or are not candidates for fluorouracil, oxaliplatin, irinotecan, and if Kras wild-type, anti EGFR therapy. * Considered an appropriate candidate for regorafenib therapy. * Measurable disease or evaluable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Measurable computed tomography (CT) scan evidence of liver metastases which are not treatable by surgical resection or local ablation with curative intent at the time of study entry. * ECOG Performance Status score of 0-1. * Adequate hematologic, renal and liver function. * Male patients with female partners of childbearing potential and women female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. * Life expectancy ≥ 3 months. * Ability to understand the nature of this study and give written informed consent Exclusion Criteria: * Most recent chemotherapy ≤14 days and ≥Grade 1 chemotherapy-related side effects, with the exception of alopecia. * Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to initiation of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required. * Wide field radiotherapy (including therapeutic radioisotopes such as strontium-89 administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy. * Previous radiation delivered to the upper abdomen. * Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. * Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. * Leptomeningeal metastases or spinal cord compression due to disease. * Pregnant or lactating. * Evidence of ascites, cirrhosis, portal hypertension, or thrombosis as determined by clinical or radiologic assessment. * History of abdominal fistula or gastrointestinal perforation ≤6 months prior to beginning study treatment. * Serious non-healing wound, active ulcer, or untreated bone fracture. * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome). * Any of the following cardiac diseases currently or within the last 6 months: * Unstable angina pectoris * Congestive heart failure (NYHA ≥ Grade 2) * Conduction abnormality not controlled with pacemaker or medication * Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible) * Valvular disease with significant compromise in cardiac function * Inadequately controlled hypertension (i.e., systolic blood pressure \[SBP\] >180 mmHg or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment). * Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. * Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C. * Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer. * Use of strong CYP34A inducers or inhibitors. * The herbal medications St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng will not be allowed during study treatment. Patients should stop using these herbal medications 7 days prior to first dose of study drug. * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. * Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Study Objectives This study aims to investigate the significance of minimal residual axillary disease following NAC, with a particular focus on micrometastases (ypNmi), in comparison to pathologic lymph node-negative (ypN0) or macrometastases (ypN+). The investigators will further explore the prognostic implications of SLNmi for the prediction of axillary LN status and survival outcomes. Conditions: Micrometastases, Neoadjuvant Chemotherapy Intervention / Treatment: PROCEDURE: Sentinel lymph node biopsy, axillary lymph node dissection Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Stage II or III primary breast cancer patients * Patients who performed neoadjuvant chemotherpay * Patients who underwent axillary lymph node dissection with or without sentinel lymph node biopsy Exclusion Criteria: * Patients who performed upfront surgery * De novo stage IV patients

Study Objectives This clinical trial is being conducted to assess whether second forward view examination of proximal colon could increase adenoma detection rate of right colon. Conditions: Colon Adenoma Intervention / Treatment: PROCEDURE: Second Examination Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SCREENING Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * all patients undergoing colonoscopy for screening in our hospital Exclusion Criteria: * previous history of resection of colon; * familial polyposis syndrome * inflammatory bowel disease * active antiplatelet or anticoagulant therapy prevent polypectomy; * pregnancy or lactating women

Study Objectives The goal of this study is to determine how often patients who have atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS) on core needle biopsy of an imaging (found by mammogram or breast ultrasound) abnormality will have associated breast cancer at surgical removal of the area. Conditions: Breast Neoplasms Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Women 20 years of age or older * Imaging abnormality necessitating a core needle biopsy * Core needle biopsy revealing ALH or LCIS * Patients may have a history of fibroadenoma and/or proliferative breast lesions with atypia Exclusion Criteria: * History and/or concomitant diagnosis of invasive breast cancer or ductal carcinoma in situ (DCIS) * A palpable abnormality diagnosed by core needle biopsy to be ALH or LCIS * Received tamoxifen in the past

Study Objectives Liposomal formulations are frequently used today in the treatment of cancer. LiPlaCis is the first targeted liposomal formulation with a tumour triggered release mechanism to undergo clinical development in oncology and it is expected that LiPlaCis will improve the therapeutic index of cisplatin compared to conventional cisplatin. Cisplatin is one of the most widely used drugs in the treatment of cancer due to its documented efficacy in a number of tumour types. Furthermore, it seems highly likely that cisplatin will remain an important drug in the future treatment of cancer. However, the drug is associated with a number of serious toxicities that complicates or necessitates discontinuation of therapy - e.g. need for pre-hydration, neurotoxicity, nausea and vomiting. Thus, there is a well-established need for improving cisplatin therapy in cancer patients. One option here is improving the formulation of the drug, so that a more selective up-take of cisplatin administered takes place at the tumour sites. Based on the results of the pre-clinical studies of LiPlaCis, it seems clear that LiPlaCis offers the potential to improve cisplatin therapy to the benefits of cancer patients. In a prematurely stopped Phase I Dutch study a Recommended Dose (RD) for a Phase II study was never reached which was the aim of the finished Phase I dose escalating part of this study for advanced or refractory solid tumors. In the Phase 2 part of this study, patients with advanced breast cancer with a biopsy examination showing a pattern compatible with sensitivity to LiPlaCis or patients with skin cancer will be included. Conditions: Phase 1: Advanced or Refractory Solid Tumours, Phase 2 Part: Metastatic Breast Cancer, Prostate Cancer and Skin Cancer Intervention / Treatment: DRUG: LiPlaCis Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological or cytological documented locally advanced or metastatic solid tumour relapsed on 2 or more different prior therapies. From step 5 and extension phase, population limited to Skin Cancer patients (non screened) or metastatic Breast Cancer patients or metastatic castration-resistant prostate cancer patients screened sensitive to LiPlaCis. * Age >= 18 years. * Life expectancy >= 3 months. * ECOG performance status of 0 - 1. * Recovered to Grade 1 or less from acute toxicities of prior treatment. * >= 6 months must have elapsed since patient received cisplatin. * >= 4 weeks must have elapsed since patient received any investigational medicinal product. * >= 4 weeks must have elapsed since patient received any radiotherapy(except for palliative radiotherapy on non-target lesions), or treatment with cytotoxic or biologic agents (>=6 weeks for mitomycin or nitrosoureas). No hormonal treatment is allowed except treatment with corticosteroids at physiological dose and hormonal treatment with LHRH agonists for prostate cancer. * >=2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF. * Adequate condition as evidenced by the following clinical laboratory values: * Absolute neutrophil count (ANC) >= 1,5 x 10E9/L * Haemoglobin is at least 4,6 mmol/L * Platelets >= 75 x 10E9/L * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2,5 x ULN, in case of known liver metastases ALT and AST <= 5 x ULN. Patients who does not conform to the transaminase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase levels are considered elevated due to other reasons than deteriorated liver capacity, may be considered for inclusion based on conferred agreement between PI and Sponsor * Serum bilirubin <= 1,5 ULN * Alkaline phosphatase <= 2,5 x ULN, in case of known liver metastases <= 5 x ULN. Patients who does not conform to the Alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the Alkaline phosphatase levels are considered elevated due to other reasons than deteriorated liver capacity, may be considered for inclusion based on conferred agreement between PI and Sponsor * Blood urea within normal limits, creatinine below upper normal limits and creatinine clearance within normal limits (>= 60 mL/min Cr-EDTA clearance).In the case of hydronephrosis, renography must be considered prior to treatment with LiPlaCis. For signs of drainage obstacle, well-functioning renal excretion/effect and normal diuresis must be ensured, e.g. via a double-J catheter. * Sexually active males and females of child-producing potential, must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards. * Patient must understand the investigational nature of this study and sign an independent ethical committee (IEC) approved written informed consent form prior to any study related activities. Exclusion Criteria: * Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease). * Any active infection requiring parenteral or oral antibiotic treatment. * Known infection with human immunodeficiency virus (HIV) or hepatitis virus. * Pre-existing renal insufficiency. Please refer to inclusion criteria no. 10g. * Active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or symptomatic arrhythmias currently requiring medication. * Known or suspected active central nervous system (CNS metastasis). (Patients stable 8 weeks after completion of treatment for CNS metastasis are eligible). * Autoimmune disease. * Impending or symptomatic spinal cord compression or carcinomatous meningitis. * Pre-existing neuropathy, i.e., Grade >1 neuromotor or neurosensory toxicity (as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4,0), except for abnormalities due to cancer. * Known hypersensitivity to cisplatin or liposomes. * Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy(except for palliative radiotherapy on non-target lesions). * Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry). * Unwilling or unable to follow protocol requirements. * Previous progression on a platinum containing therapy.

Study Objectives This study will evaluate the impact of a whole-of-community multi-level adaptive systems intervention on implementation of community change and youth population physical activity. Building on local health department partnerships, the investigators will conduct a two-wave staggered-start community randomized trial with four volunteer rural communities (each having nested school, after-school, scouting/4-H club, youth sport organizations) randomly assigned to intervention or standard public health practice. Conditions: Physical Activity Intervention / Treatment: BEHAVIORAL: Wellness Landscape Intervention, BEHAVIORAL: Standard Practice Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Community located in rural micropolitan area * Community is a one high school town * Organization is a school district * Organization is a after school program * Organization is a youth club system * Organization is a youth sport delivery system * Leaders of settings in school, after-school, club, and youth sport * 3rd through 6th grade settings and children within Exclusion Criteria: *

Study Objectives The objective of our study is to determine which factors affect willingness to participate in gynecologic oncology clinical trials. Women with a diagnosis of gynecologic malignancy will be approached to complete a survey assessing willingness to participate in clinical trials. The validated Attitudes and Randomized Trials Questionnaire (ARTQ) will be used to assess willingness to participate. Conditions: Cancer, Clinical Trials Intervention / Treatment: OTHER: Survey Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Diagnosis of gynecologic malignancy * English or Spanish literate Exclusion Criteria: * Prior enrollment in a clinical trial * Currently pregnant * Currently incarcerated

Study Objectives The investigators aimed to research the incidence of hyperlactatemia in craniotomy cases, the relationship of lactate elevation with tumor type and other factors that may be related, and whether the general anesthesia method applied (inhalation anesthesia or total ıntravenous anesthesia) affects lactate level. Conditions: Intracranial Neoplasm, Hyperlactatemia, Brain Tumor, Hypoperfusion Location: Turkey Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Scheduled to undergo elective craniotomy for an intracranial mass * adult patients Exclusion Criteria: * emergency * In situations that may cause hyperlactatemia (such as sepsis, hepatic or renal failure, shock state, or patients who need inotropic support)

Study Objectives Principal objective is to evaluate the impact of Thalidomide to prolong the duration of response after autologous transplantation for myeloma Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Thalidomide, DRUG: Biphosphonates Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * de novo myeloma * according to Durie and Salmon classification stage II, III and stage I with a lytic bone lesion * patients from 18 to 65 years old * beta2microglobulin < 3 mg/l or del13 absent * signed informed consent * eligible for transplantation Exclusion Criteria: * peripheral neurological toxicities * uncontrolled or severe cardiovascular disease * other malignancy except basocellular carcinoma or FIGO stage I carcinoma of the cervix * patient who received biphosphonate during the last 60 days * renal failure definited as creatinine > 150 µmol/l * patient with obvious vascular cerebral medical history * liver dysfunction definited as bilirubin > 35 µmol/l or ASAT, ALAT, PAL > 4N * respiratory dysfunction * HIV + * Patient who refused to use an acceptable barrier method for contraception

Study Objectives This protocol corresponds to a prospective, multicentre, open label, phase II study designed to evaluate the efficacy of CPX-351 in elderly patients with secondary or high-risk AML. The clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles) and follow-up periods and consists of a single arm group. Patients will be enrolled at diagnosis to follow the treatment arm. After that will start induction chemotherapy with CPX-351 regimen (14 days maximum screening period). Once a patient have been evaluated for response and recovered from major complications, he/she will start second course (consolidation 1), unless the bone marrow and peripheral blood assessment is showing less than a complete response, then a second induction may be offered. If a CR or CRi is obtained after the second induction course, patients will start the third course after a rest and recovery period. Patients aged between 60 and 65 years old are recommended to undergo an allo-SCT after first consolidation if they are considered fit for this procedure and they have a full matched related or unrelated donor. Patients aged between 65 and 70 years old can be proposed for an allo-SCT in CR/CRi if they have a composite HSCT co-morbidity index /age less than 4 and a suitable fully matched related donor. In patients over 70 years old, an allo-SCT in first CR should be avoided although the decision should be taken on an individual basis. Patients with CR/CRi who are not considered for an allo-SCT, will follow 6 maintenance cycles with modified courses of CPX-351 schedule. Patients showing unacceptable toxicity along all therapeutic phases that, in consideration of the investigator, will be prematurely discontinued. All patients will be followed-up for survival. The study will be analyzed on an intention to treat basis. Bone marrow and response assessments will be done after each induction and consolidation course, and every 3 months during the first 12 months after starting maintenance therapy. Patients will be followed-up for a minimum period of 1 year after the enrolment of the last patient. Additionally, after the end of the trial, patients will be followed-up for 2 years in order to verify survival and the evolution of the disease. Study design allows a maximum of 59 patients. Conditions: Newly Diagnosed Secondary or High Risk AML Intervention / Treatment: DRUG: CPX-351 Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: OTHER Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. Informed consent form must be signed by the patient and the investigator. * Age 60 to 75 years at the time of diagnosis of AML. * Newly confirmed diagnosed of AML according to WHO 2008 criteria. * Secondary or high risk AML, defined as one of the following: * t-AML: documentation of prior cytotoxic therapy or radiation therapy for an unrelated disease in a discharge summary or pharmacy records or radiation therapy records * MDSAML: bone marrow documentation of MDS prior to diagnosis of AML (could have been treated previously with hypomethylating or standard chemotherapy) * CMMoLAML: bone marrow documentation of CMMoL prior to diagnosis of AML (could have been treated previously with hypomethylating or standard chemotherapy) * de novoAML with FISH or cytogenetic changes linked to MDS per WHO 2016 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Ability to adhere to the study visit schedule and other protocol requirements. * Laboratory values fulfilling the following: * Serum creatinine < 2.0 mg/mL * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin < 3 times the upper limit of normal (ULN, subjects with elevated liver enzymes related to disease were instructed to contact the Sponsor) (subjects with Gilbert's Syndrome were instructed to contact the sponsor). * Subjects with second malignancies in remission may have been eligible if there was clinical evidence of disease stability for a period ≥ 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies at screening. Subjects maintained on long-term nonchemotherapy treatment such as hormonal therapy were eligible. * Cardiac ejection fraction ≥ 50% assessed by echocardiography or MUGA. * Eligible to receive intensive chemotherapy. * Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception for three months after their last dose of medication. Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential). * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures Exclusion Criteria: * Patients with genetic diagnosis of acute promyelocytic leukemia. * Age <60 years or >75 years. * Blastic phase of bcr/abl chronic myeloid leukemia. * Patients with de novo AML without FISH or cytogenetic changes linked to MDS per WHO 2016 criteria. * Clinical evidence of active central nervous system (CNS) leukemia. * Subjects with active (uncontrolled, metastatic) second malignancies. * Any major surgery or radiation therapy in 4 weeks. * Subjects with myocardial impairment of any cause (eg, cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging). * Uncontrolled infection; subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) could be entered into the study provided the subject was respiratory and hemodynamically stable for ≥ 72 hours. * Current evidence of invasive fungal infection (blood or tissue culture); subjects with recent fungal infection must have had subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values). * Hypersensitivity to cytarabine, daunorubicin or liposomal products. * Presence of any severe psychiatric disease or physical condition that, according to the physician´s criteria, contraindicates the inclusion of the patient into the clinical trial. * Serum creatinine ≥ 20 mg/dL (unless it is attributable to AML activity). * Bilirubin, alkaline phosphatase, or SGOT > 3 times the ULN (unless it is attributable to AML activity). * Subjects with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent). * History of Wilson's disease or other copper-metabolism disorder. * Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to grade 1 or less; if the half-life of the agent is unknown, patients must wait 4 weeks prior to first dose of study treatment.

Study Objectives Determine the safety and efficacy of novel suture in esophageal anastomosis. Specific Aims: 1) Determine the safety of using STRATAFIX suture in esophagogastric anastomosis by measuring anastomotic leak rate; and 2) Determine efficacy of STRATAFIX suture in esophagogastric anastomosis by measure anastomotic stricture rate. Conditions: Esophageal Cancer Intervention / Treatment: DEVICE: Stratafix PGA Suture Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * All patients with esophageal cancer who are deemed candidates for minimally invasive robot assisted Ivor Lewis esophagogastrostomy. * Patients who provide written informed consent for the study. Exclusion Criteria: * Any patient with esophageal cancer who is not deemed a surgical candidate or who is not deemed a candidate for the Ivor Lewis technique of esophagectomy (with intrathoracic anastomosis). * Any patient less than 18 years of age

Study Objectives A First-in-human, dose-escalation, dose-expansion phase I clinical study of JS004 in subjects with recurrent/refractory malignant lymphoma in China, to evaluate the safety, tolerbility, PK, immunogenicity,antitumor activity and biomarkers of JS004, to define MTD and RP2D of JS004. A cycle is 21 days(3 weeks) which includes JS004 being administered IV Q3W and JS004 combine with JS001 being administered IV Q3W. All patients will be treated until disease progression per Lugano response critieria 2014 for Lymphoma or intolerable toxicity per CTCAE 5.0, withdrawal of consent, or end of the study, whichever occurs first. Disease progression must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of progression. Conditions: Recurrent/Refractory Malignant Lymphoma Intervention / Treatment: BIOLOGICAL: JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion, BIOLOGICAL: Drug：JS001, Intravenous infusion Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: *Able to understand and sign informed consent voluntarily *18-70 years old *Pathologically confirmed malignant lymphoma *ECOG PS: 0-1 *Expected survival ≥12 weeks *At least one measurable lesion per Lugano response critieria 2014 for Lymphoma *Adequate organ and marrow function, as defined below: ANC≥1.5×109/L; PLT≥100×109/L and ≥75×109/L for subjects with bone marrow involvement; Hb≥90 g/L; TBIL≤1.5 ULN, ≤2 ULN in those with hep109atic metastasis, except subjects with documented Gilbert's syndrome who must have a baseline conjugated bilirubin ≤3.0 mg/dL; AST and ALT≤2.5 ULN, ≤5 ULN in those with hepatic metastasis; Cr≤1.5 UL, or creatinine clearance≥50mL/min for subject; INR ≤2 ULN and aPTT≤1.5×ULN for those with no prior anticoagulant therapy. *According to Fridericia's principle, QTC results need to match : Male≤450 ms，Female≤470 ms *Females of childbearing potential need to use effective contraception Exclusion Criteria: * Patients with known allergy to macromolecular protein preparations or JS004 components * Prior exposure to anti-BTLA or anti-HVEM antibodies * Enrolled in other clinical studies within 4 weeks prior to the first dose of study treatment * Major surgery within 4 weeks prior to the first dose of study treatmentor still recovering from prior surgery * Patients who discontinued previous immunotherapy due to immune-related adverse reactions * Immunosuppressive agents have been used within 4 weeks prior to the first dose of study treatment * Prior allogeneic bone marrow transplantation or solid organ transplantation * Live attenuated vaccine be administered 30 days before the first dose of study treatment * Two or more malignancies developed within 5 years prior to first dose of study treatment * The patients have symptomatic, untreated, or requiring ongoing treatment central nervous system (CNS) metastases * Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia.Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor. * Autoimmune disease within the previous 2 years * A history of rapid allergic reaction, eczema, or asthma beyond the control of topical corticosteroids * A history of primary immunodeficiency * Concomitant disease that is not under control, including but not limited to: persistent or active infection, unexplained fever > 38.5°C, or heart disease, active peptic ulcer disease or gastritis * A history of active inflammatory bowel disease * HIV(+) * Patients with evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection * Pregnant or lactating woman * Patients with vitiligo, alopecia, and hormonal replacement therapy have controlled endocrine defects * Any other medical factors that may affect subjects' rights, safety, compliance, ability to sign informed consent, and interpretation of study results. * Have a history of psychotropic drug abuse and unable to withdraw or have mental disorders.

Study Objectives 1. Verify the effect of Erlotinib concurrent whole-brain radiation therapy as first-line treatment for patients with multiple brain metastases from non-small-cell lung cancer to compare with WBRT alone. 2. Verify pre-built EGFR mutation prediction model for NSCLC brain metastases Conditions: Multiple Brain Metastases, Non-small-cell Lung Cancer Intervention / Treatment: DRUG: Erlotinib, DRUG: WBRT Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * 18 years of age or older; * the pathological diagnosis of non-small cell lung cancer and detection of pulmonary primary ARMs / sequencing EGFR mutation; * enhanced MRI showed brain metastases ≥ 2 or NSCLC of brain metastases after resection of residual lesions in ≥ 2 / intracranial metastases in patients with new; * if the previous use of EGFR-TKIs, in an WBRT synchronous Erotinib before treatment to disable EGFR-TKIs ≥ 4 weeks; * expected survival period over 2 months; * KPS score ≥ 70; * GPA score 0.5 - 3.5; * a week before randomization, bone marrow and liver and kidney function in patients with meet the following criteria: 1. HB ≥ 100, g/L ≥ 1.5 × 109/L neutrophil and platelet ≥ 100 × 109/L; 2. total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal; 3. more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min, urea N ≤ 200mg/L; 4. Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg. * compliance research plan and follow-up process, and be able to carry out oral therapy; * in women of childbearing age, must be in before starting treatment within 7 day of urine pregnancy test and the result is negative, and not in the lactation period, and reproductive age men and women prior to entry into the study, the research process until 90 days after stopping all agree to use reliable methods of contraception; * can understand and consent. Exclusion Criteria: * patients have been treated with radiation to the brain or to erlotinib and its ingredients allergies; * mixed with small cell lung cancer patients with components; * 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor); * before entering the group 4 weeks received any other investigational drugs; * judgment according to the researchers, there are serious harm to patient safety or affect the patients completed the study with the disease, and patient compliance with the difference; * had any clinical evidence of moderate to severe chronic obstructive pulmonary disease (COPD -COPD a history or risk factors of pulmonary function testing, FEV1/FVC<70%, FEV1<80% estimates, with or without chronic cough, sputum, difficulty breathing), activity of interstitial lung disease (-ILD pulmonary function test FEV1/FVC<70%, FEV1<80% estimates, dispersion carbon monoxide lung volume -DLCO<40%, high resolution CT showed a diffuse interstitial lung disease) disease activity and other researchers decided; * on gastrointestinal physiology is not perfect, or absorb the obstacle syndrome, or unable to tolerate oral medication, or active peptic ulcer; * any unstable system diseases: including active infection, uncontrolled hypertension, unstable angina pectoris, within the last 3 months of the onset of angina, congestive heart failure, the group in June before the myocardial infarction, need serious mental disorder drug treatment, liver, kidney or metabolic diseases; mental / spiritual diseases such as Alzheimer's disease; * without full control of ocular inflammation or eye infections, or any may cause the eye disease situation; * known human immunodeficiency virus (HIV) infection; * with immunodeficiency disease, or suffer from other acquired, congenital immunodeficiency disease, or a history of organ transplantation; * any disease, metabolic disorders, or physical examination or laboratory suspicion or treatment of complications in patients at high risk of drug.

Study Objectives The purpose of this study is to assess the safety and tolerability of iniparib administered as monotherapy or in combination regimens in patients previously treated with iniparib in a clinical study and who have derived clinical benefit after completion of the parental study's objectives. Conditions: Solid Tumors Intervention / Treatment: DRUG: Iniparib (SAR240550/BSI-201), DRUG: Carboplatin, DRUG: Doxorubicin HCL liposome injection, DRUG: Gemcitabine, DRUG: Irinotecan, DRUG: Paclitaxel, DRUG: Topotecan Location: Spain, Belgium, Italy, United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria : * Cancer patients greater than 18 years of age who have completed all assessments required to meet the primary objectives of a parental phase 1, 2 or 3 clinical study of iniparib as monotherapy or in a combination regimen. * Previously received and are continuing to derive clinical benefit from iniparib, as monotherapy or in combination with chemotherapy, as determined by the treating physician. * Ongoing treatment with iniparib at time of parental study completion/closure and meet criteria to initiate a subsequent cycle of therapy, as described in the parental study protocol. * On a stable parental study regimen (at least one cycle for the regimen at the dose/schedule that is to be given in the Treatment Extension study must have been given prior to the patient's discontinuation from the parental study). Signed written informed consent. Exclusion criteria: * Patient has not previously participated in any clinical trial of iniparib. * Patient has evidence of progressive disease while receiving iniparib. * Patient has another concurrent invasive malignancy (aside from the malignancy for which the patient has received therapy for on the parental protocol). * Patient has a major medical or co-morbid condition(s) that the investigator believes might compromise safe participation in the study (such as uncontrolled lung, kidney, or liver problems; uncontrolled infection; a history of congestive heart failure; or an electrocardiogram suggesting significant problems with the heart). * Patient has not recovered to baseline or less than Grade 1 from non-hematologic adverse events related to any anticancer therapy received prior to signing informed consent on the Treatment Extension study, with the exception of hair loss. * Patient is receiving concurrent treatment with other investigational agents not allowed as part of the combination regimen in the parental study protocol. * Concurrent anticancer treatment with any agent other than iniparib and any co-administered chemotherapeutic agent(s) specified on the parental study protocol are not permitted throughout the course of the study. * Patient is receiving concurrent radiation therapy to treat primary disease with curative intent. (Note that palliative radiotherapy is allowed as long as there is no evidence of progressive disease.) * Patient is unable to comply with the requirements of the study. * Pregnant or breast-feeding women. * Women of childbearing potential or men with partners of childbearing potential who are not protected or who are unwilling to use an effective contraceptive method of birth control during the course of the study and for a period of 6 months following the last dose. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Objectives The purpose of this study is to determine whether cessation of hormone replacement therapy for one or two months before a screening mammogram will improve its performance by decreasing breast density. Conditions: Breast Cancer Intervention / Treatment: OTHER: temporary discontinuation of hormone therapy for 1 month, OTHER: temporary discontinuation of hormone therapy for 2 months Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: DIAGNOSTIC Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * 1 or more prior screening mammograms at Group Health Cooperative within the past 2 years * Currently taking HRT * Taking HRT at prior screening mammogram * Due for a screening mammogram Exclusion Criteria: * BI-RADS breast density of 1 (entirely fat) * Previous cardiovascular events (heart surgery, catheterization, stent bypass, angioplasty, stroke, DVT) * Previous breast cancer * History of breast implants * Breast reduction since last mammogram * Mastectomy * History of using Tamoxifen or Raloxifene * Declined contact or use of data for research

Study Objectives This is a randomised, double-blind, cross-over study of pazopanib versus sunitinib in patients with locally advanced or metastatic renal cell carcinoma (mRCC) who have received no prior systemic therapy for advanced or metastatic RCC. Approximately 160 eligible patients will be stratified based on the ECOG performance status (0 vs. 1) and number of metastatic sites of disease (0 and 1 vs. \>=2). The study consists of two treatment periods of 10 weeks with a 2-week wash-out period between the two treatment periods. Patients will receive pazopanib and sunitinib treatment sequentially in a double-blinded fashion. The primary objective of the study is to assess how the tolerability and safety differences between pazopanib and sunitinib translate into patient preference, defined by the patient's stated preference for which drug they may prefer to continue treatment with at end of study. The secondary objectives are to evaluate the reason for patient preference as assessed by a patient preference questionnaire; to evaluate fatigue as assessed by FACIT-Fatigue and quality of life as assessed by EuroQoL EQ-5D; to evaluate dose modifications and time to dose modification; and to evaluate safety. Conditions: Carcinoma, Renal Cell Intervention / Treatment: DRUG: pazopanib, DRUG: sunitinib Location: Italy, Germany, France, Finland, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Masking: QUADRUPLE

Inclusion Criteria: * Patients must provide written informed consent prior to performance of any study-specific procedures or assessments and must be willing to comply with treatment and follow up. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging study) and obtained prior to signing of informed consent may be utilised for screening or baseline purposes provided these procedures are conducted as specified in the protocol. * Received no prior systemic therapy (including interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC. Patients who received adjuvant treatment with a cancer vaccine are eligible. * Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma of any histology (equivalent to Stage IV RCC according to AJCC staging). Patients with non-measurable disease are allowed if metastatic disease can be confirmed. * ECOG PS of 0 or 1 * Age >= 18 years * A female is eligible to enter and participate in this study if she is of: Non-childbearing potential (i.e. physiologically incapable of becoming pregnant) Childbearing potential, including any female who has had a negative serum pregnancy test within two weeks prior to the first dose of study treatment, preferably as close to the first dose as possible and agrees to use adequate contraception. * Adequate organ system functions * Total serum calcium concentration <12.0mg/dL * Left ventricular ejection fraction (LVEF) >=lower limit of institutional normal (LLN) as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan. The same modality used at baseline must be applied for subsequent evaluations. * Patient is able to swallow and retain oral tablets Exclusion Criteria: * Poor MSKCC risk group * History of another malignancy. Note: Patients who have had another malignancy and have been disease-free for 3 years or patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. * History or clinical evidence of central nervous system (CNS) metastases. Note: Patients who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible: * Are asymptomatic, * Have had no evidence of active CNS metastases for >=6 months prior to enrolment , * Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC). * Any clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product including, but not limited to: * Malabsorption syndrome * Major resection of the stomach or small bowel that could affect the absorption of study drug * Active peptic ulcer disease * Inflammatory bowel disease * Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. * Presence of uncontrolled infection. * Corrected QT interval (QTc) >480 msecs using Bazett's formula * History of one or more of the following cardiovascular conditions within the past 6 months: * Cardiac angioplasty or stenting * Myocardial infarction * Unstable angina * Coronary artery bypass graft surgery * Symptomatic peripheral vascular disease * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) * Poorly controlled hypertension (defined as systolic blood pressure (SBP) of > 150mmHg or diastolic blood pressure (DBP) of > 90mmHg) at baseline. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour within a visit. The mean SBP/DBP values from each blood pressure assessment must be <=150/90mmHg in order for a patient to be eligible for the study. * History of cerebrovascular accident (CVA) including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. * Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major). * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels. * Evidence of active bleeding or bleeding diathesis. * Significant haemoptysis within 6 weeks prior to first dose of study drug. * Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study. * Use any prohibited medications within 14 days of the first dose of study medication. * Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug. * Radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of study treatment. * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib. * Pregnant or lactating female Female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.

Study Objectives Fatigue is frequently identified as one of the most troublesome symptoms in cancer patients and there are very few conventional therapies which can address the symptom of fatigue in patients who are undergoing cancer treatment. This study will be testing whether the administration of a complementary therapy (individualized homeopathy) to a patient undergoing chemotherapy treatment is feasible and whether this treatment can lessen the fatigue symptoms of adults. The study will also test whether the n-of-1 study design is feasible in this population. Conditions: Fatigue, Effects of Chemotherapy Intervention / Treatment: OTHER: Homeopathic medicine, OTHER: Unmedicated lactose/sucrose globule Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: QUADRUPLE

Inclusion Criteria: * Diagnosed with any type of cancer. Patient may have newly diagnosed, relapsed or a second malignant disease. * Receiving any type of cytotoxic chemotherapy with 6 or more cycles post study enrollment administered intermittently every two or three weeks with no planned radiation treatment. * Is experiencing fatigue due to the chemotherapy treatments. (or has a score of 2 or higher on the fatigue item of the Symptom Distress Scale) * Above 18 years of age. * Able to ingest medications in lactose/sucrose globule or liquid form. Exclusion Criteria: * Previous history of allergy to the homeopathic products. * Pregnant or lactating

Study Objectives The purpose of the trial is to test the efficacy of combining conventional chemoradiotherapy with radiosurgery for locally advanced pancreas cancer. Conditions: Pancreatic Cancer Intervention / Treatment: DEVICE: Stereotactic Radiosurgery (Cyberknife) 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:- Pancreatic tumors not to exceed 7.5 cm. * Histologically confirmed malignancies of the pancreas, (ampulla of Vater or periampullary duodenum, tumors may be included when the head of pancreas is secondarily involved and unresectable criteria are met). * Unresectable by CT criteria or unresectable at exploratory laparotomy or laparoscopy. CT criteria for unresectability include encasement of the superior mesenteric vein (SMV), portal vein (PV) or invasion of the celiac artery or superior mesenteric artery (SMA). * Patients with metastatic disease may be treated if they are symptomatic from the primary tumor. * Eastern Clinical Oncology Group performance status 0, 1 or 2. Exclusion Criteria:Chemotherapy within 1 month of registration.

Study Objectives The goal of this clinical research study is to learn if abraxane can help to control colorectal and/or small bowel cancer. The safety of this drug will also be studied. Abraxane is designed to block cancer cells from dividing, which may cause them to die. Conditions: Colorectal Cancer, Cancer of Gastrointestinal Tract Intervention / Treatment: DRUG: Abraxane 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: * Patient must have histologically or cytologically confirmed colorectal adenocarcinoma or small bowel adenocarcinoma * Metastatic disease documented on diagnostic imaging studies with measurable disease per RECIST version 1.1. * Refractory disease defined as: a) prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-epidermal growth factor receptor (EGFR) therapy if Kirsten rat sarcoma (KRAS) wildtype for colorectal adenocarcinoma and; b) prior treatment with fluoropyrimidine and oxaliplatin for small bowel adenocarcinoma. * Colorectal adenocarcinoma patients must be known to have CpG island methylator phenotype. CIMP-high phenotype will be defined as hypermethylation at 2 or more of the 6 methylation-specific PCR markers (hMLH1, P16, P14, MINT1, MINT2, and MINT31). * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. * Adequate organ function including: a) Absolute neutrophil count (ANC) =/>1,500cells/mm\^3; b) Platelets =/>100,000/ul; c) Hemoglobin >9.0 g/dL; d) Total bilirubin =/<1.5mg/dL In patients with known Gilbert's syndrome, direct bilirubin =/<1.5 x upper limit of normal (ULN) will be used as organ function criteria, instead of total bilirubin; e) AST and ALT < 2.5 x ULN; f) Alkaline phosphatase <2.5x ULN; g) Creatinine <1.5 gm/dL. * Negative serum or urine pregnancy test in women with childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization, within one week prior to initiation of treatment. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. * A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom. * Patients must sign an Informed Consent and Authorization indicating that they are aware of the investigational nature of this study and the known risks involved. * Patient is =/>18 years of age on the day of consenting to the study. Exclusion Criteria: * Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)". * Prior treatment with taxane therapy for either colorectal cancer or small bowel adenocarcinoma. * Chemotherapy or any other investigational agents within 14 days of first receipt of study treatment, or major surgery within 28 days of first receipt of study treatment, or palliative radiation within 7 days of first receipt of study treatment. * Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection. * Pregnancy (positive pregnancy test) or lactation. * Patients with carcinomatous meningitis. * Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.

Study Objectives This phase I/II trial studies the side effects and best dose of hydroxychloroquine when given together with palbociclib and letrozole before surgery in treating patients with estrogen receptor positive, HER2 negative breast cancer. Hydroxychloroquine is a substance that decreases immune responses in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Drugs, such as letrozole, may lessen the amount of estrogen made by the body. Giving hydroxychloroquine, palbociclib, and letrozole before surgery may work better than palbociclib and letrozole in treating patients with breast cancer. Conditions: Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage IV Breast Cancer AJCC v8 Intervention / Treatment: DRUG: Hydroxychloroquine, DRUG: Letrozole, DRUG: Palbociclib 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: * Signed written informed consent * Diagnosis of estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Postmenopausal defined by: a. Age >= 55 years and 1 year or more of amenorrhea b. Age < 55 years and 1 year or more of amenorrhea with luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) levels in the postmenopausal range c. Age < 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range d. Chemotherapy or medically induced ovarian suppression with 1 year or more of amenorrhea and with LH and/or FSH levels in the postmenopausal range e. Status after bilateral oophorectomy (>= 28 days prior to first study treatment) * Absolute neutrophil count (ANC) >= 1500 cells/ul * Platelet count >= 100,000/ul * Serum creatinine concentration < 1.5 x upper limit of normal (ULN) * Bilirubin level < 1.5 x ULN * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN * Alkaline phosphatase =< 2.5 ULN * Metastatic cohorts (Phase I): Diagnosis of stage IV estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by ASCO/CAP criteria * Metastatic cohorts (Phase I): Must be a candidate for treatment with CDK4/6 inhibitor and hormonal therapy with an aromatase inhibitor as standard of care * Metastatic cohorts (Phase I): No prior exposure to CDK 4/6 inhibitors * Neoadjuvant cohorts (Phase II): Diagnosis of stage I-III estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by ASCO/CAP criteria. If stage I, clinical tumor size must be >= 1.5 cm * Neoadjuvant cohorts (Phase II): Baseline tumor Ki67 > 5% * Neoadjuvant cohorts (Phase II): Surgical candidate and appropriate for pre-operative endocrine therapy Exclusion Criteria: * Prior exposure to CDK 4/6 inhibitor therapy * History of retinal disease or active visual disturbances (normal baseline study-specified retinal exam required) * Acute illness, including infections requiring medical therapy, known bleeding diathesis or need for anticoagulation * Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken: a. Oral estrogens, including hormone replacement therapy (but prior depot estrogen use not allowed). b. Investigational agents (or 5 half-lives, whichever is longer) * Required concomitant use of any drug that is a strong CYP3A inhibitor or inducer * Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol * Life expectancy of less than 6 months * Pregnancy, lactation or planning to be pregnant. * Neo-adjuvant cohorts (Phase II): Prior therapy for breast cancer (medical, surgical or radiation therapy) * Neo-adjuvant cohorts (Phase II): Clinical T4 disease * Neo-adjuvant cohorts (Phase II): Inoperable or metastatic breast cancer based on standard evaluation

Study Objectives This phase I trial studies the side effects and the best dose of nivolumab when given together with gene-modified T cells and vaccine therapy in treating patients with solid tumors that express the cancer-testes antigen NY-ESO-1 gene AND have spread from where it started to nearby tissue or lymph nodes (locally advanced) or distant organs (stage IV). T cells are a special type of white blood cells (immune cell) that have the ability to kill cancer cells. Nivolumab may block PD-1 which is found on T cells and help the immune system kill cancer cells. Placing a modified gene for the NY-ESO-1 T cell receptor (TCR) into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Dendritic cells are another type of blood cell that can teach other cells in the body to look for cancer cells and attack them. Giving a dendritic cell vaccine with the NY-ESO-1 protein may help dendritic cells teach the immune system to target cancer cells expressing that protein, and further help the T cells attack cancer. Giving nivolumab together with gene-modified T-cells and dendritic cell vaccine may teach the immune system to recognize and kill cancer cells that express NY-ESO-1. Conditions: Adult Solid Neoplasm, Childhood Solid Neoplasm, Metastatic Neoplasm Intervention / Treatment: BIOLOGICAL: Aldesleukin, DRUG: Cyclophosphamide, DRUG: Fludarabine Phosphate, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Nivolumab, BIOLOGICAL: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL, BIOLOGICAL: NY-ESO-1(157-165) Peptide-pulsed Autologous Dendritic Cell Vaccine, PROCEDURE: Positron Emission Tomography 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: * Stage IV or locally advanced histologically confirmed solid tumors for which no alternative therapies with proven survival advantage are available * At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists; patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion * NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly available NY-ESO-1 antibodies * Human leukocyte antigen (HLA)-A\*0201 (HLA-A2.1) positivity by molecular subtyping * Age greater than or equal to 16 years old * A minimum of one measurable lesion defined as: * Meeting the criteria for measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) * Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Absolute neutrophil count >= 1.5 x 10\^9 cells/L * Platelets >= 100 x 10\^9/L * Hemoglobin >= 9 g/dL * Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (=< 5 x ULN, if documented liver metastases are present) * Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome) * Creatinine < 2 mg/dl (or a glomerular filtration rate > 60) * Must be willing and able to accept two leukapheresis procedures * Must be willing and able to provide written informed consent Exclusion Criteria: * Previously known hypersensitivity to any of the agents used in this study * Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol * History of, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.); patients will be eligible if prior autoimmune disease is not deemed to be active (e.x. fibrotic damage of the thyroid after thyroiditis or its treatment, with stable thyroid hormone replacement therapy); vitiligo will not be a basis for exclusion * History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin * Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed) * Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist * Hepatitis B or C seropositivity with evidence of ongoing liver damage; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist * Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol * Known clinically active brain metastases; prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment and there are no neurological signs of potential brain metastases * Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 24 hours from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators; patients who are breastfeeding are not allowed on study * Since IL-2 is administered following cell infusion: * Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multi gated acquisition scan \[MUGA\], dobutamine echocardiogram, or other stress test) * Similarly, patients who are >= 50 years old with a baseline LVEF < 45% will be excluded * Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT interval \[QTC\] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions \[PVCs\] per minute), ventricular tachycardia, third (3rd) degree heart block will be excluded from the study unless cleared by a cardiologist * Patients with pulmonary function test abnormalities as evidenced by a forced expiration volume in one second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded * Evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only * Received 3 or more prior myelotoxic treatment regimens * Bone marrow involvement based on CT or PET scan at screening

Study Objectives An open label, dose-escalation study to evaluate safety, tolerability, maximum tolerated dose (MTD), efficacy, and pharmacokinetics (PKs) of CPI-613 given twice weekly for three consecutive weeks in cancer patients The objectives of this study are: * To determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks. * To determine pharmacokinetics of CPI-613 following intravenous (IV) administration. * To observe the anti-tumor effects of CPI-613, if any occur. Conditions: Advanced Cancer, Metastatic Cancer, Lymphoma, Solid Tumors, Advanced Malignancies Intervention / Treatment: DRUG: CPI-613 Location: Canada, United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have advanced and/or metastatic, histologically or cytologically documented solid tumors and lymphomas, for whom there is no available therapy shown to provide clinical benefit. * Karnofsky Performance Status (KPS) of >70%. * Must be ≥18 years of age. * Expected survival >3 months. * Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation. (Note: Pregnant patients are excluded because the effects of CPI-613 on a fetus are unknown.) * Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists. * Mentally competent, ability to understand and willingness to sign the informed consent form. * No radiotherapy, treatment with cytotoxic agents (except CPI-613), or treatment with biologic agents within the 3 weeks prior to treatment with CPI-613. At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤Grade 1 are eligible, but must be documented as such. * Laboratory values ≤2 weeks must be: * Adequate hematologic (white blood cell \[WBC\] ≥3500 cells/mm\^3 or ≥3.5 bil/L; platelet count ≥100,000 cells/mm\^3 or ≥100 bil/L; absolute neutrophil count \[ANC\] ≥1500 cells/mm\^3 or ≥1.5 bil/L; and hemoglobin (Hgb) ≥9 g/dL or ≥90 g/L). * Adequate hepatic function (aspartate aminotransferase \[AST/SGOT\] ≤3x upper normal limit \[UNL\], alanine aminotransferase \[ALT/SGPT\] ≤3x UNL (≤5x UNL if liver metastases present), bilirubin ≤1.5x UNL). * Adequate renal function (serum creatinine ≤2.0 mg/dL or 177 µmol/L). * Adequate coagulation (International Normalized Ratio or INR must be ≤1.25). Exclusion Criteria: * Serious medical illness, such as significant cardiac disease (symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity. * Patients with active central nervous system (CNS) or epidural tumor. * Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease). * Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown). * Lactating females because the potential of excretion of CPI-613 into breast milk. (Note: Lactating females are excluded because the effects of CPI-613 on a nursing child are unknown.) * Fertile men unwilling to practice contraceptive methods during the study period. * Life expectancy less than 3 months. * Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients. * Unwilling or unable to follow protocol requirements. * Dyspnea with minimal to moderate exertion. Patients with large and recurrent pleural, or peritoneal effusions requiring frequent drainage (e.g. weekly). Patients with any amount of clinically significant pericardial effusion. * Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, arrhythmias requiring medication, or symptomatic congestive heart failure. * Albumin <2.5 g/dL or <25 g/L. * Evidence of active infection, or serious infection within the past month. * Patients with known HIV infection. * Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 3 weeks prior to initiation of CPI-613 treatment. * Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment. * Requirement for immediate palliative treatment of any kind including surgery. * Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months. * A marked baseline prolongation of QT/QTc interval (e.g., repeated exhibition of a QTc interval >470 ms.). * A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of Long QT Syndrome). * Troponin I above institution limit of normal or Left Ventricular Ejection Fraction (LVEF) below 35%.

Study Objectives In this phase II trial the investigators plan to incorporate two targeted agents, bevacizumab and everolimus, into the first-line multimodality therapy of glioblastoma. In the first portion of the treatment, bevacizumab will be added to standard concurrent radiation therapy plus temozolomide. After completing radiation therapy, patients will continue treatment with the combination of bevacizumab and everolimus. Conditions: Glioblastoma Multiforme Intervention / Treatment: RADIATION: Radiation therapy, DRUG: Temozolomide, DRUG: Bevacizumab, DRUG: Bevacizumab, DRUG: Everolimus Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age >=18 years. * Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4). * Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma. * No previous treatment with radiotherapy or systemic therapy. Local therapy with a Gliadel wafer placed at the time of surgical debulking is permitted. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate bone marrow function * Adequate liver function: * Serum creatinine <=1.5 x institutional ULN. * Ability to swallow whole pills. * Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment and for 6 months after the last study treatment. Hormonal contraceptives are not acceptable as a sole method of contraception. Female patients must not breast feed. * INR <1.3 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of everolimus and monitored at least weekly, or as defined by the local standard of care, until INR is stable. * Fasting serum cholesterol <=300 mg/dL OR <=7.75 mmol/L AND fasting triglycerides <= 2.5 x institutional ULN. Exclusion Criteria: * New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix B) or symptomatic congestive heart failure. * Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg). * History of myocardial infarction or unstable angina within 6 months prior to beginning study treatment. * History of stroke or transient ischemic attack within 6 months prior to beginning study treatment. * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to beginning study treatment. * Prior history of hypertensive crisis or hypertensive encephalopathy. * History of hemoptysis (>=1/2 teaspoon of bright red blood per episode) within 1 month prior to beginning study treatment. * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1. * Serious, non-healing wound, active ulcer, or untreated bone fracture. * Proteinuria as demonstrated by urine dipstick for proteinuria >=2+. For patients with >=2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible. * Minor surgical procedures (excluding placement of a vascular access device), fine-needle aspirations, or core biopsies within 7 days prior to starting treatment. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting protocol treatment or anticipation of need for major surgical procedure during the course of study treatment. Patients who have not recovered from the side effects of any major surgery are not eligible. * Treatment with any investigational agents within 4 weeks of study entry. * Chronic, systemic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled steroids are allowed. * Other malignancies within the past 3 years except for adequately treated carcinoma in situ of the cervix or basal cell or superficial squamous (skin cell) carcinomas.

Study Objectives The purpose of the study is to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, is safe and has beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who are not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT). Conditions: Myelodysplastic Syndrome (MDS) Intervention / Treatment: DRUG: sabatolimab, DRUG: azacitidine, DRUG: venetoclax Location: Spain, Italy, Greece, Germany, France, Belgium, Hungary Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study * Age ≥ 18 years at the date of signing the informed consent form (ICF) * Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al 2012): * Very high (> 6 points) * High (> 4.5-6 points) * Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017) * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: * Prior exposure to TIM-3 directed therapy or any BCL-2 inhibitor (including venetoclax) at any time * Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of treatment * Previous first-line treatment for very high risk or high risk myelodysplastic syndromes (based on IPSS-R,Greenberg et al 2012 and Arber et al, 2016) with any antineoplastic agents, approved or investigational, including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine However, a one single cycle of HMAs treatment only started prior to enrollment is allowed. * Live vaccine administered within 30 days prior to start of treatment * Current use or use within 14 days prior to start of treatment of systemic steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion, are allowed and not considered a form of systemic treatment * History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients * Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 4.5 Other protocol-defined Inclusion/Exclusion may apply.

Study Objectives Combined with magnifying endoscopy,narrow-band imaging (NBI) contrasts microvascular architecture on lesion surface.The histology of early colorectal lesions could be predicted under NBI view.However,its capability for estimating invasion depth remains to be verified.The study is based on the hypothesis:NBI can predict histology and invasion depth,combined with the verification of microvessel count and MMP-7 expression. Conditions: Colorectal Neoplasms Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * patients of early colorectal lesions with capillary pattern(CP) type II\&III,initially detected by white-light view and then examined by NBI with magnifying endoscopy. Exclusion Criteria: * lesions with CP type I; * CP type III lesions with an obvious appearance of advanced cancer; * lesions that had underwent biopsy; * patients with inflammatory bowel disease(IBD) or familial adenomatous polyposis(FAP) * patients with previous colorectal surgery; * having conditions associated with cardiac,hepatic,renal,and coagulopathy diseases.

Study Objectives According to the studies CC is successful at inducing ovulation in 50%-75% of cases, but only 30-40% becomes pregnant. The difference has been attributed to a negative action of clomifen citrate(CC) in the form of prolonged antiestrogenic effects on endometrial receptivity. For avoiding of these negative effects, giving ethinyl estradiol in sufficient dosages may be effective. The purpose of this study is comparing pregnancy rates after IUI in women who use CC alone and those who use CC in combination with ethinyl estradiol Conditions: Infertility Intervention / Treatment: DRUG: clomiphene citrate with ethinyl esteradiol, DRUG: clomiphene citrate with plasebo Location: Iran, Islamic Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * The patients with first treatment cycle * Age between 25 and 30 years, * Infertility for at least 2 years' duration, * Oligomenorrhea or amenorrhea associated with a positive Progesterone challenge test * Women with normal concentrations of prolactin, free thyroxin and thyroid-stimulating hormone (TSH) Exclusion Criteria: * Women whose partners had an abnormal semen analysis according to World Health Organization * Women who had uterine or tubal abnormalities on hysterosalpingography, and women who had a body mass index of >30 kg/m2.

Study Objectives In this clinical trial, the investigators want to know if cabazitaxel is more effective than methotrexate for patients with recurrent or metastatic squamous cell carcinoma of the head and neck in palliative treatment. Conditions: Squamous Cell Carcinoma of the Head and Neck Intervention / Treatment: DRUG: Cabazitaxel, DRUG: Methotrexate Location: Belgium, Luxembourg Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to curative treatment with surgery and/or chemotherapy and/or radiation. * At least one measurable lesion by MRI or CT-scan according to RECIST 1.1. * Progressive disease within 1 year after first line platinum-based chemotherapy given either as a part of the multimodal curative treatment or in the palliative setting. * ECOG performance status 0 -2, in stable medical condition * Patients must have an expected survival of at least 3 months * Paraffin-embedded tumor tissue available for immunohistochemistry but not mandatory * Patients must be over 18 years old and must be able to give written informed consent. * Women of child-bearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to enrollment). * Patients must have adequate organ function (Hemoglobin ≥ 9 g/100 ml, Neutrophils ≥ 1,500/mm3, Platelets ≥ 100,000/mm3, total bilirubin <1 time the upper limit of normal (ULN) for age, serum alanine aminotransferase (ALT) < 1.5 1.5 x ULN for age, aspartate aminotransferase (AST) < 1.5 ´ ULN for age , serum creatinine <1.5 x ULN for age. * Signed informed consent prior to beginning protocol specific procedure. * Sexually active patients must use effective contraception during the period of therapy and up to 150 days after the last treatment dose. Acceptable contraception includes, but is not limited to: oral hormone therapy, partner vasectomy, or double barrier contraception (which is defined as a male condom plus spermicide in combination with either a female condom, or diaphragm, or cervical cap or intrauterine device) Exclusion Criteria: * Non-squamous head and neck cancer * Nasopharynx cancer * More than two lines of chemotherapy for palliative treatment * Surgery or investigational drugs or chemotherapy within 4 weeks before study inclusion. Curative radiation therapy (60-70 Gy) within 8 weeks. For palliative radiation therapy (i.e 8 Gy on a painful lesion) no delay is needed. * Previous treatment with cabazitaxel * Significant active cardiac disease including: uncontrolled high blood pressure according to the CTCAE 4 grading, unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias * Other uncontrolled illnesses (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes ...) * Previous malignancy from which the patient has been disease-free for < 5years, as other than SCCHN. * Previous treatments with taxanes and/or anti-EGFR therapy are not an exclusion criteria. * Active grade > 2 peripheral neuropathy * Active grade > 2 stomatitis * Known brain or leptomeningeal involvement * History of severe hypersensitivity reaction (> grade 3) to polysorbate 80 containing drugs * Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A/5. A one-week washout period is necessary for patients who are already on these treatments. * Organic brain syndrome or significant psychiatric abnormality that would preclude participation in the full protocol and follow up.

Study Objectives MicroRNAs (MiRNAs) regulate the translation of RNAs and are implicated in cell proliferation and renewal both under physiologically normal as well as in malignant conditions. Dysregulation of specific miRNAs may be associated with either gaining oncogenic or loosing tumor suppressing functions. MiRNA dysregulation has been implicated in breast cancer tumorigenic (stem cell) and non-tumorigenic development. Therefore, miRNA profiling of treatment naïve and treatment-exposed breast tumors and sequential samples of blood/serum will allow for identification of miRNA markers of prognosis and as indicators and potential targets for personalized therapies. In this proposal, specimens from patients treated in the clinical breast cancer program on already existing protocols (IRB 05091 and 05015) will be characterized by Dr. Rossi's laboratory and collaborators, and the information gained will be applied to develop specific therapies. Conditions: Breast Cancer Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Female, * Breast Cancer * > 18 years, * regardless of histology, treatment phase, or stage Exclusion Criteria: *

Study Objectives This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting. Conditions: HER2+ Metastatic Breast Cancer (MBC) Intervention / Treatment: DRUG: neratinib, DRUG: capecitabine, DRUG: lapatinib Location: Japan, Turkey, Israel, France, Taiwan, United Kingdom, Italy, Germany, Brazil, Belgium, Austria, Sweden, Czechia, Australia, United States, Ireland, Singapore, Canada, Spain, Portugal, Argentina, Denmark, Hong Kong, Russian Federation, Netherlands, Switzerland, Finland, Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Aged ≥18 years at signing of informed consent. * Histologically confirmed MBC, current stage IV. * Documented HER2 overexpression or gene-amplified tumor immunohistochemistry 3+ or 2+, with confirmatory fluorescence in situ hybridization (FISH) +. * Prior treatment with at least two (2) HER2-directed regimens for metastatic breast cancer. Exclusion Criteria: * Received previous therapy with capecitabine, neratinib, lapatinib, or any other HER2 directed tyrosine kinase inhibitor. Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Study Objectives Current research has shown that the use of diabetes management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) in women with PCOS can not only improve glucose and lipid metabolism but can also reverse testosterone abnormalities and restore menstrual cycles. A new medicine called exenatide (Byetta) has been found to reduce body weight, as well as, improve abnormal glucose metabolism in diabetics. This randomized study will compare Exenatide (Byetta) to extended release metformin (Fortamet) to combination therapy (both Byetta and Fortamet) on menstrual cyclicity, hormone profiles and metabolic profiles over a 24-week period in women with PCOS. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DRUG: metformin, exenatide or combined (metformin & exenatide ) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria:Overweight/obese women (BMI>27) * Must have six or fewer menses /year or be amenorrheic * Have either clinical or laboratory evidence of hyperandrogenism (hirsutism or elevated testosterone (T)) and /or PCOS ovary on ultrasound Exclusion Criteria: other uncorrected endocrinopathy- hyperprolactinemia, hyper- or hypothyroidism, congenital adrenal hyperplasia or presence of overt diabetes alterations in hepatic or renal function use of hormonal medications, insulin sensitizers or medications that interfere with carbohydrate metabolism for at least 8 weeks Known active substance abuse including tobacco and alcohol. Pregnancy, breastfeeding or desire for pregnancy during study interval (6 months *

Study Objectives The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and toripalimab in patients with advanced hepatocellular carcinoma (HCC) Conditions: Hepatocellular Carcinoma Intervention / Treatment: PROCEDURE: Hepatic arterial infusion chemotherapy, DRUG: Lenvatinib, DRUG: Toripalimab Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL) * Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. * Barcelona clinic liver cancer-stage C * Eastern Cooperative Oncology Group performance status of 0 to 2 * With no previous treatment * No Cirrhosis or cirrhotic status of Child-Pugh class A only * Not amendable to surgical resection ,local ablative therapy and any other cured treatment. * The following laboratory parameters: Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 32 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 * Ability to understand the protocol and to agree to and sign a written informed consent document Exclusion Criteria: * Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy * Known history of HIV * History of organ allograft * Known or suspected allergy to the investigational agents or any agent given in association with this trial. * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * Evidence of bleeding diathesis. * Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. * Known central nervous system tumors including metastatic brain disease

Study Objectives This is a Phase II study to test the efficacy of exogenously administered GM-CSF in prostate cancer patients who have failed definitive local therapy, and have only serologic (PSA) evidence of progression. Conditions: Prostate Cancer Intervention / Treatment: DRUG: GM-CSF 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: * Histologic diagnosis of adenocarcinoma of the prostate; stage T1-T3, N0-N1, M0 * Prior definitive therapy for primary prostate cancer consisting of:external beam radiotherapy;brachytherapy with or without pelvic external beam radiation; or radical prostatectomy with or without adjuvant or salvage radiation therapy * Therapeutic PSA response to primary therapy below 1.0 ng/ml post radiation therapy or below 0.4 ng/ml for radical prostatectomy * Patients treated with adjuvant or salvage radiation therapy following radical prostatectomy are eligible provided:Post prostatectomy PSA was never > 6.0 ng/ml, last effective day of androgen deprivation is at least 3 months prior to study entry * Recurrent PSA level elevation (between 0.4 ng/ml and 6.0 ng/ml) on two determinations at least one week apart. * No clinical evidence of gross local recurrence or known metastatic disease other than PSA elevation. Transrectal ultrasound and/or biopsy to evaluate local recurrence is not required. All patients will receive a bone scan and CT scan of the abdomen to exclude metastases. * Estimated life expectancy of at least 6 months. * ECOG Performance status of 0 or 1. * Willing and able to give informed consent. Exclusion Criteria: * Cryosurgery as definitive therapy of primary tumor. * Any metastasis. * No concurrent or prior malignancy is allowed except for the following: adequately treated basal or squamous cell skin 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. * Current systemic steroid therapy (inhaled or topical steroids acceptable). * Prior hormonal therapy for treatment of progressive disease. * Prior chemotherapy, immunotherapy, or therapy with other experimental agents for prostate cancer. * Any surgery within the prior 4 weeks. * Bilirubin and SGOT > 2 x upper limit of normal. * BUN and serum creatinine > 2.0 times normal. * No active congestive heart failure. * If there is a history of clinically significant obstructive airway disease, a DLCO must exceed 50%. * Active uncontrolled bacterial, viral or fungal infection until these conditions are corrected or controlled. * Any underlying medical condition which in the principal investigator's opinion will make the administration of GM-CSF hazardous or obscure the interpretation of adverse events. * PSA > 6.0 ng/ml

Study Objectives The study was conducted based on randomized controlled experimental design with double-blind, pre-test-post-test to determine the effect of Reiki applied to pediatric oncology patients aged 5-7 years on pain, vital signs, oxygen saturation (SpO2) and quality of life. While the population of the study consisted of oncology patients aged 5-7 years who were hospitalized in the pediatric oncology services between December 2020 and November 2021, the sample consisted of 66 children diagnosed with leukemia who met the sample selection criteria. The research consists of 3 groups. These groups are Reiki group (n=22), Placebo group (n=22), control group (n=22). The data are collected using Introductory Information Form, Wong-Baker FACES Pain Scale (W-BPS), Vital Signs Follow-up Form, The Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module Child and Parent Form. Reiki was applied to the Reiki group for 20-30 minutes for three consecutive days and Placebo was applied to the sham Reiki group by an independent nurse during the same application period. The children in the control group were like the routine of the ward. Conditions: Reiki Intervention / Treatment: OTHER: Reiki, OTHER: Placebo Location: Turkey Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Being treated in the pediatric oncology service at the time of the study * Being between 5-7 years old * Body temperature being within normal limits * To have received at least 1 course of chemotherapy * Absence of visual, auditory problems or mental retardation at a level that can fill the scales, Exclusion Criteria: * To have taken analgesic medication in the last 6 hours, * Have received any energy and body-mind therapy (yoga, reiki, massage, meditation, healing touch) in the last six months

Study Objectives The purpose of this study is to compare overall survival in participants with metastatic colorectal cancer treated with either ramucirumab and FOLFIRI or placebo and FOLFIRI. Conditions: Colorectal Cancer Intervention / Treatment: BIOLOGICAL: Ramucirumab, BIOLOGICAL: Placebo, DRUG: Irinotecan, DRUG: Folinic Acid, DRUG: 5-Fluorouracil Location: Japan, Israel, France, Taiwan, Hungary, Italy, Germany, Brazil, Belgium, Austria, Slovenia, Sweden, Czechia, Australia, United States, India, Spain, Portugal, Argentina, Greece, Denmark, Netherlands, Puerto Rico, Finland, Romania, Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Histologically or cytologically confirmed colorectal cancer, excluding primary tumors of appendiceal origin (participants are eligible to enroll irrespective of KRAS mutation status) * Confirmed metastatic colorectal cancer (Stage IV) * The participant has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and, a) Experienced radiographic disease progression during first-line therapy, or b) Experienced radiographic disease progression ≤6 months after the last dose of first-line therapy, or c) Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression ≤6 months after the last dose of first-line therapy. Note that a participant must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy; in addition, a participant must have received at least 1 cycle of first-line therapy that included bevacizumab, oxaliplatin and a fluoropyrimidine in the same cycle. Note that a participant must not have received more than 2 different fluoropyrimidines as part of a first-line regimen; disease progression is not an acceptable reason for discontinuing 1 fluoropyrimidine and starting a second fluoropyrimidine * Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted). For participants with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen. Note that rechallenge with oxaliplatin is permitted and will be considered part of the first-line regimen for metastatic disease, both initial oxaliplatin treatment and subsequent rechallenge are considered as 1 regimen * Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Adequate hematologic, renal and hepatic function * Adequate coagulation function \[International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be on a stable dose of anticoagulant therapy and if on oral anticoagulation, must have an INR ≤3 and have no clinically significant active bleeding or pathological condition that carries a high risk of bleeding * Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available * Ability to provide signed informed consent Exclusion Criteria: * Receipt of bevacizumab ≤28 days prior to randomization * Receipt of any investigational therapy for non-oncology clinical indication ≤28 days prior to randomization * Receipt of any previous systemic therapy, other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic colorectal cancer * Known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression (currently or in the past) * Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to, myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤12 months prior to randomization * Pregnant (confirmed by serum beta human chorionic gonadotropin (ß HCG) test ≤7 days prior to randomization) or lactating * History of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization * Acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator * Grade 3 or higher bleeding event ≤3 months prior to randomization * Experience of any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, Grade 4 hypertension, Grade 3 proteinuria, a Grade 3-4 bleeding event, or bowel perforation * Known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1\*6/\*6, UGT1A1\*28/\*28, or UGT1A1\*6/\*28 * Known allergy to any of the study treatment components, including any components used in the preparation of ramucirumab, or other contraindication to receive the study treatments * Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis

Study Objectives This was a multi-institutional, multinational, open-label, single-arm Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of trastuzumab emtansine (trastuzumab-MCC-DM1) administered by intravenous (IV) infusion in combination with pertuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive locally advanced or metastatic breast cancer who had previously received trastuzumab. Conditions: Metastatic Breast Cancer Intervention / Treatment: DRUG: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg, DRUG: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg, DRUG: Pertuzumab 420 mg Location: Spain, United States, Italy, Germany, France, Canada, Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically documented human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. * Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments. * Prior trastuzumab in any line of therapy. * No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy. * Measurable disease. * For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study. * Life expectancy ≥ 90 days. Exclusion Criteria: * Less than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal, or radiotherapy for the treatment of breast cancer, with the following exceptions: Hormone-replacement therapy or oral contraceptives; palliative radiation therapy involving ≤ 25% of marrow-bearing bone if administered ≥ 14 days prior to first study treatment. * History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued. * Peripheral neuropathy of Grade ≥ 2. * History of clinically significant cardiac dysfunction. * Current severe, uncontrolled systemic disease, eg, clinically significant cardiovascular, pulmonary, or metabolic disease. * Brain metastases that are untreated, progressive, or have required any type of therapy to control symptoms from brain metastases within 60 days of the first study treatment. * History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.

Study Objectives Advanced biliary tract adenocarcinoma has a poor prognosis with limited therapeutic options. Nab-paclitaxel plus S-1 chemotherapy will be given to untreated patients with advanced biliary tract adenocarcinoma for the first-line treatment. Conditions: Biliary Tract Cancer Intervention / Treatment: DRUG: Nab-paclitaxel,S-1 Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age, years: 18-70 * Histologically and cytologically confirmed advanced biliary tract adenocarcinoma, unresectable, measurable lesions according to RECIST criteria; ECOG score of 0-1; life expectancy ≥12 weeks; * Untreated; more than 6 months after the last adjuvant chemotherapy (does not include taxanes and S1); * Laboratory examination within 14 days before entering the study should meet following requirements: ANC ≥ 1.5 x 10\^9/L; PLT ≥ 100 x 10\^9/L; Hb ≥ 90g/L (9g/dL); AST, ALT ≤ 2.5 x ULN (with no liver metastasis), ≤ 5 x ULN（with liver metastasis); creatinine ≤ 1.5 x ULN; TBIL ≤ 1.5 x ULN * Both male and female subjects of potential fertility have to agree effective birth control during the entire study * Informed consent Exclusion Criteria: * Concurrent other effective treatment (including radiotherapy) * Resectable patients * Allergy history to other drugs in the same class patients with pregnancy or lactation * Known severe internal medical diseases * Abnormal heart function or relevant history of myocardial infarction and severe arrhythmia * Immunocompromised patients, such as HIV positive * Uncontrollable mental illness * Other conditions the researchers considered ineligible for the study

Study Objectives Comparing the structural effects of TNFi and tocilizumab on the periarticular bone by performing a comprehensive analysis of the periarticular bone changes in RA patients treated with either TNFi or tocilizumab in a longitudinal Setting, using high-resolution peripheral quantitative computed tomography (HR-pQCT), a very sensitive method for visualizing and quantifying bone microstructure in RA patients. Quantitatively assessing the changes of erosions volume, osteophytes size and the area of cortical fenestration in a group of TNFi-treated and a group of tocilizumab- treated RA patients. Conditions: Rheumatoid Arthritis Intervention / Treatment: DRUG: Tocilizumab, DRUG: TNF-alpha Inhibitor Location: Germany Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Females and males with RA erosions in the wrist and/or MCP joints * Must be aged ≥ 18 years at time of consent * Stable treatment with conventional DMARDs of at least 3 months Exclusion Criteria: * Patients exposed to abatacept or rituximab in the last 12 months * Patients receiving glucocorticoids over 5 mg prednisolone per day * Patients who are younger than 18 years * Pregnant or lactating females * Patients having received an HR-pQCT examination during the last 6 months before screening

Study Objectives This is a retrospective cohort study aiming to collect data on patients' characteristics, resource utilization, adverse events management and calculate costs attributed to current treatments of advance RCC patients who have received at least one prior VEGF-targeted therapy in Taiwan from National Health Insurance (NHI) perspective. Conditions: Renal Cell Carcinoma Metastatic, Renal Cell Carcinoma Location: Taiwan Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with confirmed diagnosis of clear-cell renal cell carcinoma * Patients with evidence of metastatic disease * Patients who have received at least one previous VEGFR-targeted therapy, i.e sunitinib, pazopanib or sorafenib * Patients who received care at the selected medical centers, utilizing the National Health Insurance (NHI) reimbursed system at the time of the disease Exclusion Criteria: * Patients enrolled in any clinical trial involving anti-cancer therapy * Pregnant woman

Study Objectives Assess the safety and tumor response of utilizing an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine given in combination with standard of care (SoC) checkpoint inhibitors (CPI) in patients with stage IV melanoma with measurable disease. Conditions: Metastatic Melanoma Intervention / Treatment: DRUG: TLPLDC Vaccine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * 18 years or older * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix A) * Metastatic melanoma eligible for {or currently on} standard of care CPI therapy (treating physician's choice) with measurable disease. * Approximately 1 cm3 preferred but 1 mg minimum of accessible and dispensable tumor (minimum of 3 passes with a core needle) * Able to tolerate CPI treatment regimen {if already started} * Adequate organ function as determined by the following laboratory values: * ANC ≥ 1,000/μL * Platelets ≥ 75,000/μL * Hgb ≥ 9 g/dL * Creatinine ≤ 1.5 x upper limit of normal (ULN) or Creatinine clearance ≥ 50% of lower limit of normal (LLN) * Total bilirubin ≤ 1.5 ULN * ALT and AST ≤ 1.5 ULN * For women of child-bearing potential, agreement to use adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms) Exclusion Criteria: * Inability to tolerate CPI therapy {if already started} * Rapidly progressing multi-focal metastatic melanoma * Insufficient tumor available to produce vaccine * ECOG >2 performance status (Appendix A) * Immune deficiency disease or known history of HIV, HBV, HCV * Receiving immunosuppressive therapy including chronic steroids (except physiologic maintenance doses), methotrexate, or other known immunosuppressive agents * Pregnancy (assessed by urine HCG) * Breast feeding * Active pulmonary disease requiring medication to include multiple inhalers (>2 inhalers and one containing steroids) * Involved in other experimental protocols (except with permission of the other study PI)

Study Objectives This is a research study for subjects who have been diagnosed with Adult T cell Leukemia/Lymphoma, a rare and aggressive peripheral T cell neoplasm caused by the virus HTLV1. Currently, there is no accepted standard therapy for this disease. The purpose of this research study is to evaluate the use of the investigational drug lenalidomide in the treatment of Adult T cell Leukemia/Lymphoma. Lenalidomide is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental. Conditions: Adult T Cell Leukemia/Lymphoma Intervention / Treatment: DRUG: Lenalidomide 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 at the time of signing the informed consent form. * Able to adhere to the study visit schedule and other protocol requirements. * Relapsed or refractory HTLV-1 associated Adult T-cell Leukemia/Lymphoma (Acute and lymphoma subtypes) * All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. * ECOG performance status of ≤ 2 at study entry (see Appendix C). * Laboratory test results within these ranges: * Absolute neutrophil count ≥ 1000/mm³ * Platelet count ≥ 50,000 /mm³ * Calculated creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault formula (Appendix J). Patients with calculated creatinine clearance ≥ 30 mL/min and < 60 mL/min will have a reduced starting dose of lenalidomide (see Section 5.4.2). * Total bilirubin ≤ 1.5 x ULN * AST (SGOT) and ALT (SGPT) ≤ 3 x ULN. * Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix B: Education and Counseling Guidance Document. * Patients at high risk for DVT/PE must be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin). Exclusion Criteria: * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide). * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome (see Appendix H). Subjects may be enrolled upon correction of electrolyte abnormalities. * Use of any other experimental drug or therapy within 28 days of baseline. * Known hypersensitivity to thalidomide. * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Any prior use of lenalidomide. * Concurrent use of other anti-cancer agents or treatments. * Known positive for HIV or infectious hepatitis, type B or C. * Recent DVT/PE requiring dose adjustments of anticoagulation within past 90 days

Study Objectives This is a multicenter, blinded prospective study of 2,000 women undergoing mammography for breast -related symptoms or signs. Breath tests will be performed in order to demonstrate that the outcome of mammography results combined with breast test results improves clinical sensitivity and specificity in a group that has an increased prior probability of cancer. Breath will be collected and analyzed with a rapid point-of-care instrument (BreathLink™) and also with a laboratory-based assay of samples collected into an inflatable bag (BreathBag™). Conditions: Breast Cancer Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Female aged 18 years or over * Referred for mammography for a breast-related concern (e.g. breast mass, nipple discharge etc.) * Understands the study, and is willing to give written informed consent to participate * Approves collection of relevant additional data for clinical research record if and when it becomes available, including results of mammogram and any other imaging studies, biopsy results, TNM staging, and other relevant biomarker data e.g. status of BRCA1, BRCA2, HER2 and receptors (ER+ or ER-) and progesterone (PgR+ or PgR-) Exclusion Criteria: * Known serious or potentially life-threatening disease (e.g. severe cardiac or infectious disease) * Previous history of treated breast cancer, or cancer of any other site, with the exception of basal cell carcinoma of skin.

Study Objectives The main purpose of the study is to evaluate a safe, tolerable recommended Phase II dose (RP2D) and/or the maximum tolerated dose (MTD) of M3814 when given in combination with avelumab with and without radiotherapy in participants with selected advanced solid tumors. Conditions: Oncology, Solid Tumors Intervention / Treatment: DRUG: M3814, DRUG: M3814, DRUG: Avelumab, RADIATION: Radiotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Part A and Part FE (M3814 + avelumab): Participants must have histologically or cytologically proven advanced or metastatic solid tumors for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to provide clinical benefit for their condition * Part B (M3814 + Radiotherapy \[RT\] + avelumab): histologically or cytologically proven advanced or metastatic solid tumors for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to provide benefit for their condition and are amenable to receive RT * Part A, B and FE: Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 at study entry * Part A, B and FE: Female participants of childbearing potential should be willing to use a highly effective contraceptive method * Part A, B and FE: Male participants should agree to refrain from donating sperm plus, either: abstain from any activity that allows for exposure to ejaculate * Use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy * Part A, B and FE: Be willing to provide informed consent for the trial * Other protocol defined inclusion criteria could apply Exclusion Criteria: * Participants who have received prior chemotherapy, hormonal anticancer therapy with the exception of luteinizing hormone-releasing hormone analogs, biologic therapy, or any other anticancer therapy within 28 days of the first dose of study treatments (6 weeks for nitrosoureas or mitomycin C) * Participants who have undergone major surgery for any reason, except diagnostic biopsy, within 4 weeks of the study intervention and/or has not fully recovered from the surgery within 4 weeks of the study intervention * Participants with evidence of active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent * Participants with brain metastases, except those meeting the following criteria: a) brain metastases that have been treated locally and are clinically stable for greater than or equal to (>=) 4 weeks prior to randomization 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) c) participants must be either off steroids or on a stable or decreasing dose of less than (<) 10 milligrams (mg) daily prednisone (or equivalent) * Participants with severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year), psychiatric or substance abuse disorders; or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results * Participants requiring systemic immunosuppressive agents (such as steroids) for any reason who cannot be tapered off these drugs before start of study intervention, with the following exceptions: a) participants with adrenal insufficiency, may continue corticosteroids at physiologic replacement dose, equivalent to less than or equal to (<=) 10 mg prednisone daily b) participants requiring steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) is permitted c) participants with previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon planned to be completed in 14 days, or that the dose after 14 days will be equivalent to <= 10 mg prednisone daily * Participants with a history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome, Hepatitis B virus or Hepatitis C and with history of infection must have a polymerase chain reaction (PCR) documentation that infection is cleared * Participants who have received a live vaccine within 30 days prior to the first dose of trial treatment * Participants with known prior severe hypersensitivity to any of the investigational products or any component in its formulations * Participants with evidence of additional malignancy within the last 5 years unless a complete remission without further recurrence was achieved at least 2 years prior to study entry and participants were deemed to have been cured with no additional therapy required or anticipated to be required. Participants with treated nonmelanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate may participate * Participants pretreated with immunotherapy who have, any history of dose limiting toxicities (DLTs) with prior immunotherapy agents, including Grade 3/4 immune-related adverse events (irAEs); irreversible irAEs; Grade greater than or equals to (>=) 3 irAEs that did not respond to steroid rescue; or neurologic irAE with significant clinical sequelae * Participants with irAE requiring hormone replacement therapy (e.g., thyroxine, insulin, or physiologic dose of corticosteroid replacement therapy for adrenal or pituitary insufficiency) may participate as long as the endocrinopathy is well controlled and the participant is not otherwise symptomatic from hormone insufficiency * Physiologic corticosteroid dose is defined as <= 10 mg daily of prednisone or equivalent * for Part B only: * Participants who have confirmed esophagitis and in whom radiation planning target volume will include any portion of the esophagus, the participant is not eligible unless an esophageal endoscopy rules out the presence of esophagitis * Participants in whom more than 10 percent (%) of the total esophagus volume might receive more than 15 gray (Gy) (50% of the prescribed radiotherapy \[RT\] dose) * Participants who have had previous radiotherapy to the same region as intended to be irradiated in this study within the past 12 months * Participants who have had extensive previous radiotherapy on >= 30% of bone marrow reserve or prior bone marrow/stem cell transplantation within 5 years before study start * If participant hepatic metastatic lesion is selected to be irradiated: - the non-tumor liver volume < 700 milli liters (mL); - Child-Pugh score >= 8 * Other protocol defined exclusion criteria could apply

Study Objectives This is a randomized, open-label and parallel phase I study to compare pharmacokinetics (PK), pharmacodynamics (PD) and safety of goserelin acetate sustained-release microspheres for injection (LY01005) and ZOLADEX® following multiple administration in patients with prostate cancer. Conditions: Prostate Cancer Intervention / Treatment: DRUG: LY01005, DRUG: ZOLADEX® 3.6 mg Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * 18 years or older. * Patients with locally advanced or metastatic prostate cancer suitable for endocrine therapy, including those who are suitable for endocrine therapy (such as patients with biochemical recurrence after adjuvant endocrine therapy and radical therapy) following radical therapy. * Serum testosterone level ≥ 150 ng/dL (1.50 ng/mL or 5.2 nmol/L) at the screening visit. * Life expectancy of at least 9 months. * ECOG score of ≤ 2. * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelet count ≥ 90 x 10\^9/L, white blood cell count ≥ 3 x 10\^9/L, hemoglobin ≥ 90 g/L, total bilirubin (TBIL) ≤ 1.5×ULN, ALT and AST ≤ 2.5×ULN (or ≤ 5.0×ULN for patients with liver metastases), and Creatinine clearance ≥50 mL/min at the screening visit. * Subjects of childbearing potential must agree to use a reliable method of contraception with their female sexual partners during the study period and at least 3 months after the last administration. * Patients who voluntarily sign an IRB-approved informed consent form before any trial-related activities, are willing to abide by the restrictions of the study, and complete the prescribed examinations. Exclusion Criteria: * Patients with prostate cancer who receive previous or ongoing endocrine therapy (surgical castration or other endocrine therapy including GnRH receptor agonists, GnRH receptor antagonists, anti-androgens, estrogens, megestrol acetate, etc.), except for patients with prostate cancer undergoing prostatectomy, radiotherapy or cryotherapy who have received neoadjuvant/adjuvant endocrine therapy for no more than 6 months and discontinued the above therapy more than 6 months before screening. * Patients with confirmed or suspected hormone-resistant prostate cancer. * Patients who have received prostatic surgery within 4 weeks prior to the first dose, or plan to receive major surgical treatment during the trial. * Patients who have previously received hypophysectomy or adrenalectomy, or who have pituitary lesions or adrenal dysfunction. * History of severe asthma, anaphylaxis, or severe urticaria and/or angioedema. * Other cancer diseases diagnosed within 5 years before the screening visit, except for surgically removed basal or squamous cell carcinoma of the skin. * History of the following medical histories within 6 months prior to the screening visit: stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina, coronary revascularization, New York Heart Association (NYHA) class ≥ II cardiac insufficiency, severe unstable arrhythmia. * Hypertensive patients with poor blood pressure control (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg at the screening visit). * Patients with type 1 diabetes or type 2 diabetes with poor glycemic control (glycosylated hemoglobin > 8% at the screening visit). * Patients who have received treatment with 5-α reductase inhibitors (finasteride, dutasteride, enalidomide, epristeride, etc.) within 4 weeks before the first dose. * Has previously received goserelin. * Is receiving coumarin anticoagulants at the screening visit. * Has congenital long QT syndrome or QT/QTc interval prolongation (QTc ≥ 450 ms) at the screening visit; Or has received drugs that may prolong QT/QTc interval at the screening visit. * Known to be allergic to the active ingredients or any excipients of GnRH agonists or bicalutamide. * Patients who are seropositive for hepatitis B surface antigen (HBsAg), and must meet the following 2 conditions at the same time: 1. HBV DNA level: HBeAg-positive patients, HBV DNA ≥ 20,000 IU/ml \[equivalent to 10\^5 copies/mL\]; HBeAg-negative patients, HBV DNA ≥ 2,000 IU/ml \[equivalent to 10\^4 copies/mL\]; 2. ALT ≥ 2 x ULN); Patients who are seropositive for human immunodeficiency virus (HIV) antibody. * Alcoholics or drug abusers. Alcoholics are defined as drinking more than 14 units of alcohol per week within 3 months prior to the screening visit (1 unit = 350 mL beer, or 45 mL liquor, or 150 mL wine). * Has participated in any clinical trials of investigational drugs or medical devices, and discontinued within 1 month or 5 half-lives of the corresponding drug before the screening visit, whichever is longer. * Other conditions considered unsuitable for enrollment by the investigator (such as spinal cord compression due to prostate cancer metastatic lesions of pyramid, pulmonary interstitial disease or other serious diseases).

Study Objectives Early detection of lung cancer and early removal of the cancer nodules facilitates the diagnosis and treatment. However, not all nodules are malignant. Currently the standard method to diagnose lung cancer is to remove any suspicious nodules from the lung in a surgical procedure. This study is being conducted to evaluate the performance of a laboratory test to detect changes in lung cells that might be an early indicator of lung cancer. The test uses mucus (sputum) which is collected in a non-invasive method. This study will compare the results of the lung biopsy with the laboratory test to determine if the test can detect cancer or the lack of cancer. The laboratory test will not be shared with the treating physician or the patient as the current standard for lung cancer diagnosis is a biopsy. Approximately 330 patients will be enrolled in the study. There is one visit involved and includes the collection of a sputum specimen by coughing into a cup. The medical records of patients who are negative for cancer by biopsy will be reviewed for 2 years to detect any changes in diagnosis. Conditions: Lung Cancer Location: United States, Israel Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Subjects with 0.8-3 cm solitary pulmonary nodules with high probability for malignancy * Candidate is scheduled to undergo lung biopsy procedure to determine clinical diagnosis, such as Bronchoscope biopsy, Electromagnetic Navigation Bronchoscopy, fiber optic Bronchoscopy, Needle biopsy, CT guided, Percutaneous Transthoracic Needle biopsy, Transthoracic Needle Biopsy, Open biopsy for Diagnostic Resection or Video-Assisted Thorascopic Surgery. * Candidate who is capable of undergoing sputum induction. * Ability to understand the investigational nature of the study and sign the informed consent. Exclusion Criteria: * Subjects who pose a high clinical risk for diagnostic bronchoscopy or transthoracic biopsy for definitive diagnosis. * Subjects already diagnosed with lung cancer, or previously treated for lung cancer. * Subjects who experienced pneumonia within last 12 weeks. * Subjects who experienced an acute respiratory infection within the last 2 weeks * Cases without sufficient documentation of diagnosis or follow-up will not be included. * Treatment for, or evidence of any cancer other than nonmelanoma skin cancer or carcinoma in situ within the last 3 years. * Subject who lack the capacity to consent.

Study Objectives Cancer genetic counseling (CGC) has been found to have "substantial" benefits for individuals with breast cancer and their family members; it has been deemed by multiple organizations as "standard of care" for women with breast cancer and their relatives. Unfortunately, there is a disparity in access to CGC, especially among women who live in rural and underserved areas. In North Carolina, only two cancer genetic counselors practice in rural clinics - each only for a few days per month. Therefore, in an effort to make CGC more widely available in a timely manner, we propose to test provision of counseling through telemedicine (TM), in which a patient and health care provider communicate with each other using videoconferencing. In 4 rural oncology clinics, we will implement low-cost TM and compare satisfaction and cost-effectiveness between groups of women designated to have their CGC session by TM or FTF. We'll use a validated measure to assess satisfaction by a phone survey one week after the CGC appointment; cost-effectiveness will be measured at project's end by calculating length of wait time for appointment and costs of equipment, labor, and mileage. Study hypothesis: TM is as satisfactory as FTF counseling and is a more cost-effective way to provide this beneficial service. Conditions: Hereditary Breast and Ovarian Cancer Syndrome, Lynch Syndrome Intervention / Treatment: OTHER: Telemedicine, OTHER: Face-to-Face Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: HEALTH_SERVICES_RESEARCH Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Individuals referred for cancer genetic counseling (e.g., by medical oncologist, primary care physician or self) in one of 4 oncology clinics: Gibson Cancer Center in Lumberton, NC; Scotland Cancer Treatment Center in Laurinburg, NC; Johnston Cancer Center in Smithfield, NC; and Maria Parham Cancer Center in Henderson, NC. * Willing to be randomized to receive counseling via telemedicine or face-to-face. Exclusion Criteria: * Referred for cancer genetic counseling from any clinic other than the 4 listed above. * Unwilling to be randomized to receive counseling via telemedicine or face-to-face.

Study Objectives Symptoms such as diarrhoea and abdominal discomfort are common side effects of radiotherapy for tumours in the pelvis and usually occur within 2 weeks of starting treatment. Once the course of radiotherapy has been completed these symptoms usually subside, but in some patients they may continue and sometimes cause significant problems. It is not clear what processes are occurring to trigger such symptoms. There are a number of possibilities and we would like to investigate these further. If we can identify specific reasons for symptoms being worse in one patient compared to another, then we can try to either prevent or treat these. The aim of this study is to look for differences in the way that the bowel adapts to radiotherapy in patients who do and those who don't experience bowel symptoms during their course of radiotherapy. Conditions: Gynaecological, Urological or Rectal Cancer Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Any patient with gynaecological, bladder or rectal malignancy about to embark ona 5-6 week course of radical radiotherapy to the pelvis who is able to give informed consent Exclusion Criteria: * Patients unable or unwilling to give informed consent * Patients who have already started radiotherapy

Study Objectives The purpose of this study is to learn how blood flows to tumors in patients treated with I-125 plaque brachytherapy for uveal melanoma. Conditions: Uveal Melanoma Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Adults age 18 and older with uveal melanomas involving the ciliary body and/or the choroid undergoing I-125 plaque brachytherapy. Exclusion Criteria: * Inability to give informed consent. * Inability to maintain stable fixation for OCT imaging * Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant * A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control). * Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, subject can become eligible. * Women who are pregnant or lactating at the time of enrollment due to unknown safety of fluorescein angiography. Women that become pregnant during the course of the study may remain enrolled; however, flurorescein and ICG angiography will not be performed until they are no longer pregnant or nursing an infant.

Study Objectives Study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an aromatase inhibitor (AI) in adult subjects with HR+, HER2-negative MBC. Conditions: Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer Intervention / Treatment: DRUG: MEDI-573, DRUG: Aromatase Inhibitor Location: Spain, United States, Germany, Israel, France, Canada, Belgium, Poland, Bahamas, Hungary, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically-confirmed MBC not deemed amenable to curative surgery or curative radiation therapy * Tumors are positive for ER, PgR, or both * Tumors must be negative for HER2 (by FISH, CISH or IHC) * Female gender and age ≥ 18 years at time of study entry * Postmenopausal * Karnofsky Performance Status ≥ 70 * Life expectancy of ≥ 6 months Exclusion Criteria: * Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic therapy for advanced or metastatic disease with the following exceptions: * Prior adjuvant therapy with an AI and/or tamoxifen is allowed, provided treatment ended at least 2 weeks prior to the first dose of MEDI-573 * Prior neoadjuvant and/or adjuvant chemotherapy for breast cancer is allowed * Extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or disease that is considered by the investigator to be rapidly progressing or life threatening (eg, subjects who are intended for chemotherapy) * Active brain metastases with the exception of subject has been treated and are asymptomatic and there has been no evidence of CNS progression for at least 4 weeks of first dose of MEDI-573 * Evidence of ongoing spinal cord compression or leptomeningeal carcinomatosis * Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to ≤ Grade 1 at the time of starting study treatment * Previous treatment with agents that target the IGF receptor * History of allergy or reaction attributed to compounds of chemical or biologic composition similar to those of MEDI-573 or AI * History of another invasive malignancy within 5 years except for curatively resected nonmelanoma skin cancer or carcinoma in situ of the cervix * Poorly controlled diabetes mellitus