Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy
Brief Summary: The purpose of this study is to gather information about the use of an investigational drug called Ramucirumab in adenocarcinomas of the stomach or gastroesophageal junction.


Options:
A: Inclusion Criteria:

* Patients ≥ 18 years
* histologically confirmed inoperable locally advanced, recurrent, or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction;
* ECOG (Eastern Cooperative Oncology Group) performance status 0-2;
* adequate renal, hepatic, and hematologic function;
* measurable or nonmeasurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients with intraoperatively confirmed intraperitoneal metastases but without detectable disease in radiological studies were also eligible

Exclusion Criteria:

* HER2- positive tumors defined as either IHC 3+ or IHC 2+, the latter in combination with FISH+
* previous chemotherapy for metastatic or locally advanced disease
* surgery \<3 weeks before the onset of the study treatment
* congestive heart failure
* significant dysphagia that would preclude oral administration of capecitabine
* concurrent malignant disease, except for adequately treated tumors with high likelihood of being cured (e.g. basal cell carcinoma of the skin, cervical cancer)
* clinical evidence of brain metastases
B: Inclusion Criteria:

* ≥ 18 and ≤ 70 years of age
* Histologically confirmed advanced or metastatic adenocarcinoma of the stomach
* Have failed for 2 lines of chemotherapy
* Life expectancy of more than 3 months
* ECOG performance scale ≤ 2
* At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
* Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
* More than 4 weeks for operation or radiotherapy
* More than 4 weeks for cytotoxic agents or growth inhibitors
* Adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 109/L, neutrophil \> 2.0 × 109/L, serum creatinine ≤ 1.5mg/dl, total bilirubin within upper limit of normal(ULN), and serum transaminase≤2.5×the ULN).

Exclusion Criteria:

* Pregnant or lactating women
* History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
* Any factors that influence the usage of oral administration; Evidence of CNS metastasis
* History of another malignancy within the last five years except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
* Intercurrence with one of the following: hypertension, coronary artery disease, arrhythmia and heart failure
* Receiving the therapy of thrombolysis or anticoagulation
* Abuse of alcohol or drugs
* Allergy to the ingredient of the agent or more than two kinds of food and drug
* Less than 4 weeks from the last clinical trial
* Disability of serious uncontrolled intercurrence infection.
C: Inclusion Criteria:

* Histologically or cytologically confirmed gastric carcinoma, including gastric adenocarcinoma or GEJ adenocarcinoma
* Metastatic disease or locally recurrent, unresectable disease with measurable lymph node metastases
* Measurable disease and/or evaluable disease. Measurable disease is defined as at least one unidimensionally-measurable target lesion \[≥ 2 centimeter (cm) with conventional techniques or ≥ 1 cm by spiral computed tomography (CT)\], as defined by Response using Response Evaluation Criteria in Solid Tumors (RECIST).

Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas of known disease, or peritoneal nodules that are too small to be considered measurable by RECIST

* Experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy
* Disease is not amenable to potentially curative resection
* Participant is ≥ 18 years of age
* Participant has a life expectancy of ≥ 12 weeks
* Participant resolution to Grade ≤ 1 (or to Grade ≤ 2 in the case of neuropathy) by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
* Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1
* The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 milligrams/deciliter (mg/dL) \[25.65 micromole/liter (µmol/L)\], and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x the upper limit of normal (ULN) \[or 5.0 x the ULN in the setting of liver metastases\]
* The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 40 milliliters/minute (mL/min) (that is, if serum creatinine is \> 1.5 x the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
* The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (\[UA\]; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate \< 1000 milligrams (mg) of protein in 24 hours to allow participation in the study)
* The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1000 microliters (µL), hemoglobin ≥ 9 grams/deciliter (g/dL) \[5.58 millimoles/liter (mmol/L)\], and platelets ≥ 100,000/µL
* The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Participant on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible
* If the participant has received prior anthracycline therapy as part of his or her first-line regimen, the participant is able to engage in ordinary physical activity without significant fatigue or dyspnea
* Because the teratogenicity of IMC-1121B is not known, the participant, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods)
* Female participant of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization
* Able to provide informed written consent and is amenable to compliance with protocol schedules and testing

Exclusion Criteria:

* Documented and/or symptomatic brain or leptomeningeal metastases
* Experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to randomization
* Experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization
* Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator
* Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements
* Uncontrolled or poorly-controlled hypertension despite standard medical management
* Participant has a serious or nonhealing wound, ulcer, or bone fracture
* Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer within 2 weeks prior to randomization
* Received any investigational therapy within 30 days prior to randomization
* Undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
* Received prior therapy with an agent that directly inhibits vascular endothelial growth factor (VEGF) or VEGF receptor 2 (R-2) activity (including bevacizumab), or any antiangiogenic agent
* Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use \[maximum dose 325 milligram/day (mg/day)\] is permitted
* Participant has elective or planned major surgery to be performed during the course of the clinical trial
* Participant has a known allergy to any of the treatment components
* Pregnant or lactating
* Known to be positive for infection with the human immunodeficiency virus
* Known alcohol or drug dependency
* Participant has a concurrent active malignancy other than adequately-treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been free of disease for \> 3 years
D: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Participants with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; participants with de novo Stage IV disease are eligible)
* Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC)
* Left ventricular ejection fraction (LVEF) ≥50 percent (%) at baseline (within 42 days of randomization)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment

Exclusion Criteria:

* History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC, which must be stopped prior to randomization)
* History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
* History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (\<)12 months
* History of persistent Grade ≥2 hematologic toxicity resulting from previous adjuvant therapy
* Current peripheral neuropathy of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade ≥3 at randomization
* History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent
* Current clinical or radiographic evidence of central nervous system (CNS) metastases
* Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases
* History of exposure to cumulative doses of anthracyclines
* Current uncontrolled hypertension or unstable angina
* History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation or paroxysmal supraventricular tachycardia)
* History of myocardial infarction within 6 months of randomization
* History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
* Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
* Inadequate organ function, as defined in the protocol, within 28 days prior to randomization
* Current severe, uncontrolled systemic disease
* Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
* Pregnant or lactating women
* History of receiving any investigational treatment within 28 days of randomization
* Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
* Receipt of IV antibiotics for infection within 14 days of randomization
* Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
* Known hypersensitivity to any of the study drugs
* Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Answer: C