Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-Label Multicenter, Randomized, Phase 3 Study of S-1 in Combination With Cisplatin Against 5-Fu in Combination W/ Cisplatin in Patients W/ Advanced Gastric Cancer Previously Untreated W/ Chemotherapy for Advanced Disease
Brief Summary: This is an open-label, international, two-arm, parallel, randomized, Phase 3 study evaluating the efficacy and safety of S-1/cisplatin versus 5-FU/cisplatin in patients with advanced gastric cancer previously untreated with chemotherapy for advanced disease. Patients will be randomly assigned (1:1) to S-1/cisplatin (experimental arm) or 5-FU/cisplatin (control arm). Patients will be stratified by number of metastatic sites (one vs. more than one), locally advanced or metastatic disease, prior adjuvant therapy (yes or no), measurable or non-measurable disease, and center.


Options:
A: -INCLUSION CRITERIA:

1. Histologically or cytologically confirmed gastric adenocarcinoma.
2. Metastatic disease must be measurable by computed tomography (CT) and/or magnetic resonance imaging (MRI)

   Or

   There must be a history of positive peritoneal washings or carcinomatosis
3. All disease should be deemed resectable to negative margins (NED) based on imaging studies.

   Note: Patients with both pulmonary and peritoneal metastases will be enrolled at the discretion of the Principal Investigator.
   * Esophageal invasion \< 4cm that does not require thoracotomy (Seiwert II and III lesions).
   * Hepatic metastases (unilateral or bilateral less than or equal to 5 lesions, less than or equal to 15 cm total diameter).
   * Primary peritoneal metastases (small disease load less than or equal to P2 disease) without massive ascites or intestinal obstruction.
   * Para-aortic lymph node metastases (stations 16 a1 and/or b2).
   * Lung metastases (less than or equal to 3 unilateral/bilateral, 9 cm total diameter).
   * Patients who present with both hepatic and peritoneal metastases must have no evidence of extensive para-aortic/retro-pancreatic lymph node metastases.
4. Greater than or equal to 18 years of age.
5. Must be able to understand and sign the Informed Consent Document.
6. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.
7. Life expectancy of greater than three months.
8. Patients of both genders must be willing to practice birth control during and for four months after receiving chemotherapy.
9. Hematology:

   * Absolute neutrophil count greater than 1300/mm\^3 without the support of Filgrastim.
   * Platelet count greater than 75,000/mm\^3.
   * Hemoglobin greater than 8.0 g/dl.
10. Chemistry:

    * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to 5 times the upper limit of normal. Except in the presence of obstructive liver metastases where ALT/AST may be up to 10 times the upper limit of normal.
    * Serum creatinine less than or equal to 1.5 mg/dl unless the measured creatinine clearance is greater than 60 mL/min/1.73 m\^2.
    * Total bilirubin less than or equal to 2 mg/dl, except in the presence of obstructive metastases.
    * Prothrombin time (PT) within 2 seconds of the upper limit of normal (International Normalized Ratio (INR) less than or equal to 1.8).
11. No history of prior/other malignancies within the 2 years prior to enrollment with the exception of basal cell carcinoma.

EXCLUSION CRITERIA:

1. Prior treatment with 5-FU, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) (treatment with any of the components as separate regimens is allowable).
2. Inability to tolerate any of the chemotherapeutic agents.
3. Grade 2 or greater neuropathy.
4. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
5. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
6. Brain metastases or a history of brain metastases.
7. Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies.
8. Weight less than 40 kg.
9. Significant ascites, greater than 1000cc in the absence of peritoneal disease.
10. History of congestive heart failure and/or an left ventricular ejection fraction (LVEF) less than 40%.

    Note: Patients at increased risk for coronary artery disease or cardiac dysfunction (e.g., greater than 65yo, diabetes, history of hypertension, elevated low-density lipoprotein (LDL), first degree relative with coronary artery disease) will undergo full cardiac evaluation and will not be eligible if they demonstrate significant irreversible ischemia on stress thallium or an ejection fraction \< 40%.
11. Significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease with pulmonary function tests (PFT's) indicating an forced expiratory volume 1 (FEV1) less than 50% or a carbon monoxide diffusing capacity (DLCO) less than 40% predicted for age.

Note: Patients who have shortness of breath with minimal exertion or who are at risk for pulmonary disease (e.g., chronic smokers) will undergo pulmonary function testing and will not be eligible if their FEV1 is less than 50% of expected.
B: Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:

* Has given written informed consent
* Has histologically confirmed, unresectable, locally advanced (Stage IV) or metastatic gastric cancer, including adenocarcinoma of the gastro-esophageal junction
* Has measurable or evaluable but non-measurable disease, defined as follows:

  * Measurable Disease - Patients with measurable disease as defined by RECIST criteria, i.e., the presence of at least one measurable lesion. A measurable lesion is one that can be accurately measured in at least one dimension with the longest diameter \>_ 20 mm using conventional techniques or \>_ 10 mm using spiral Computed Tomography (CT)scan. Locally recurrent disease (other than primary) is accepted if there is at least one measurable lesion (i.e. peritoneal mass, lymph node, etc.)
  * Evaluable but Non-measurable Disease - Patients with all lesions below the limits defined above for measureable disease (i.e., longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT) excluding those patients with only a primary lesion and/or with only non-evaluable cancer such as bone metastases, ascites, pleural or pericardia effusions, lymphangitic carcinomatosis of the skin or lung, previously irradiated lesions not in progression, or peritoneal carcinomatosis \< 10 mm in diameter with conventional imaging techniques.
* No prior palliative chemotherapy is permitted. Adjuvant and /or neo-adjuvant chemotherapy is permitted if more than 12 months have elapsed between the end of adjuvant or neo-adjuvant therapy and first recurrence. This does not qualify as 1st line therapy.
* Is able to take medications orally
* Is \>_ 18 years of age
* Is at least 3 weeks from prior major surgery
* Is at least 4 weeks from prior radiotherapy
* Has a ECOG performance status 0 to 1
* Has adequate organ function as defined by the following criteria:

  * AST (SGOT) and ALT (SGPT) \<_ 2.5 x ULN; if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) \<_ 5 x ULN
  * Total serum bilirubin of \<_ 1.5 x ULN
  * Absolute granulocyte count of \>_ 1,500/mm (i.e. \>_ 1.5 x 10/L by International Units (IU)
  * Platelet count \>_ 100,000/mm (IU: \>_ 100 x 10/L
  * Hemoglobin value of \>_ 9.0 g/dL
  * Calculated creatinine clearance \>_ 60 mL/min (Cockcroft-Gault formula)
* Is willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria:

Exclude a patient from this study if he/she does not fulfill the inclusion criteria, or if any of the following conditions are observed:

* Has had a treatment with any of the following within the specified timeframe prior to study drug administration:

  * Any prior palliative chemotherapy or any previous therapy for malignancy, including any chemotherapy, immunotherapy, biologic or hormonal therapy, within the past 5 years.
  * Adjuvant or neo-adjuvant therapy within the past 12 months
  * Concurrent treatment with any investigational anti-cancer agent
  * Prior cisplatin as neo-adjuvant and /or adjuvant chemotherapy with cumulative dose \> 300 mg/m
  * \> 25% of marrow-bearing bone radiated
  * Concurrent treatment with an investigational agent or within 30 days from randomization
  * Concurrent enrollment in another clinical study
* Has a serious illness or medical condition(s) including, but not limited to the following:

  * Known brain or leptomeningeal metastases
  * Uncontrolled ascites requiring drainage at least twice a week
  * Other malignancies within the past 5 years, except adequately treated carcinoma-in-situ of the cervix or non-melanoma skin cancer
  * Myocardial infarction within the last 6 months, severe/unstable angina, congestive heart failure New York Heart Association (NYHA) class III or IV
  * Chronic nausea, vomiting or diarrhea
  * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS-related illness
  * Psychiatric disorder that may interfere with consent and/or protocol compliance
  * Known neuropathy, Grade 2 or higher
  * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgement of the Investigator would make the patient inappropriate for entry into this study
* Is receiving concomitant treatment with drugs interacting with S-1. The following drugs are prohibited because there may be an interaction with S-1:

  * Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1 activity)
  * Allopurinol (may diminish S-1 activity
  * Phenytoin (S-1 may enhance phenytoin activity)
  * Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 activity)
* Is receiving concomitant treatment with drugs interacting with 5-FU:

  * Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole(may enhance 5-FU activity)
  * Allopurinol (may diminish 5-FU activity)
  * Phenytoin (5-FU may enhance phenytoin activity)
* Is receiving concomitant treatment with drugs interacting with cisplatin:

  * Phenytoin (cisplatin may diminish phenytoin activity)
  * Aminoglycosides (should be avoided within 8 days after cisplatin administration)
  * Ethyol (may diminish cisplatin activity
* Is a pregnant or lactating female
* Has known hypersensitivity to 5-FU or cisplatin
* Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients)
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:

* Adult patients \>=18 years of age
* Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or gastro-esophageal junction
* Adenocarcinoma
* HER2-positive tumors

Exclusion Criteria:

* Previous chemotherapy for advanced/metastatic disease
* Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome
* History of cardiac disease
* Dyspnoea at rest, due to complications of advanced malignancy or other disease, or patients who require supportive oxygen therapy

Answer: B