Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double Blind, Multi-Center, Phase 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Cisplatin & Capecitabine (CX) in Combination With AMG 386 or Placebo in Subjects With Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma
Brief Summary: This is a phase 2, randomized, double blind, placebo controlled, multi-center study to estimate the improvement in progression free survival (compared to control subjects) and evaluate the safety and tolerability of AMG 386 in combination with Cisplatin \& Capecitabine in the treatment of subjects with Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma. AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.


Options:
A: Inclusion Criteria:

* Pathologically confirmed unresectable locally advanced or metastatic gastric or esophagogastric junction (EGJ) adenocarcinoma; tumors of the distal esophagus within 5 cm of the EGJ are eligible
* ECOG performance status 0 or 1
* Male or female ≥ 18 years of age

Exclusion Criteria:

* Previous systemic therapy (chemotherapy or biologic therapy) for locally advanced or metastatic gastric or esophagogastric adenocarcinoma
* Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy.
* Subjects with resectable disease or suitable for definitive chemoradiation
* Subjects with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy
* Tumors of squamous cell histology
* Known central nervous system metastases
* Clinically significant upper gastro-intestinal bleeding ≤ 30 days prior to enrollment or randomization
* Serious or non-healing wound
B: Inclusion Criteria:

* Disease Related

  * Histologically or cytologically confirmed adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus with metastatic disease
  * Measurable or non-measurable disease per RECIST Guidelines
  * Prior gastrectomy (total or partial) may be allowed as long as subjects can take oral medications and meet all other inclusion/exclusion criteria. Subjects may not take crushed or dissolved capecitabine via a feeding/gastrostomy tube
  * Palliative radiotherapy for metastatic esophageal or gastric cancer prior to study entry may be allowed as long as all toxicities from radiotherapy have resolved and the radiotherapy was not to the only site of known metastatic disease
* Demographic

  •18 years of age or older at the time the written informed consent is obtained
* General

  * Able to swallow oral medication
  * ECOG performance status of 0 or 1
* Laboratory

  * Adequate organ and hematological function as evidenced by laboratory studies prior to randomization

Exclusion Criteria:

* Disease Related

  * Prior chemotherapy for metastatic disease (1st line)
  * Less than 12 months have elapsed from completion of previous adjuvant or neoadjuvant chemotherapy or chemoradiotherapy
  * Subjects with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy
  * Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities
  * Current or prior history of central nervous system metastases
  * History of arterial or deep venous thromboembolism within 12 months prior to randomization
  * History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
  * Major surgical procedure within 28 days prior to randomization
  * Minor surgical procedure, placement of central venous access device or fine needle aspiration within 3 days prior to randomization
  * Prior malignancy except: malignancy treated with curative intent and without evidence of active disease for ≥ 3 years prior to randomization and felt to be at low risk for recurrence by treating physician, adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease, prostatic intraepithelial neoplasia without evidence of prostate cancer
  * Prior malignancy (other than in situ cervical cancer, or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization
  * Clinically significant cardiovascular diseases within 12 months prior to randomization
  * Presence of clinically significant non-healing wound, ulcer (including gastrointestinal) or fracture as judged by the investigator
  * Ongoing or clinically significant active infection as judged by the investigator
  * Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
  * Known peripheral neuropathy ≥Grade 1
  * Known dihydropyrimidine dehydrogenase deficiency
  * Known hypersensitivity to 5-FU/capecitabine
  * Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
  * Known active or chronic hepatitis
* Medications

  * Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2
  * Treatment with immune modulators such as cyclosporine or tacrolimus within 30 days prior to randomization
  * Treatment with sorivudine or its chemically related analogues
  * Anticoagulants (other than aspirin and anti-platelet agents) within 7 days prior to randomization. The concurrent use of low molecular weight heparin or heparanoids or low dose warfarin (i.e, ≤ 1 mg daily) for prophylaxis against thrombosis is acceptable while on study
* General

  * Not yet completed at least 30 days since ending other investigational device/drug trial(s), or subject is receiving other investigational treatments
  * Pregnant or is breast feeding
C: Inclusion Criteria:

* Patient has histologically confirmed Stage IV adenocarcinoma of the GEJ/stomach

Note: Adjuvant radiation plus treatment with 5-FU and leucovorin is permitted, but not required.

* Patients must have measurable disease
* Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
* Patient is greater than 18 years of age
* If present, any pre-existing (current) peripheral neuropathy must be ≤ Grade 1
* Patient's laboratory values must fall within the limits set forth in section 4.2 of the protocol
* Patient has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential)
* If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a 2 month period thereafter
* Patient (or guardian) has signed a Patient Informed Consent Form
* Patient (or guardian) has signed a Patient Authorization Form

Exclusion Criteria:

* Patient has any metastatic disease other than that defined in section 4.2 (criterion #1)
* Patient has had prior treatment that included anything other than adjuvant radiation plus treatment with 5-FU and leucovorin. Prior treatment must have been completed \> 6 months prior to registration in current study. No other prior regimens are allowed.

Note: Adjuvant radiation plus treatment with 5-FU and leucovorin is permitted, but not required.

* If present, any peripheral neuropathy is \> Grade 1
* Patient has a known hypersensitivity to Taxotere (or any drug formulated with Polysorbate-80), or Eloxatin
* Has had a prior severe infusion reaction (Grade 4) to a monoclonal antibody
* Has received prior therapy, at any time, which specifically and directly targets the EGFR pathway
* Patient is receiving concurrent immunotherapy or any other concurrent treatment for their cancer
* Has had prior stem cell or bone marrow transplant or any organ transplant with the exception of corneal transplant or cadaver bone graft
* Has a significant history of uncontrolled cardiac disease; ie, uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction (LVEF\<50%)
* Has evidence of CNS involvement (CNS imaging is not required for study enrollment unless clinically suspected CNS disease is present.)
* Patient has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection
* Patient is known to be HIV positive or have a history of hepatitis B or C
* Patient has a history of other malignancy within the last 5 years (except for squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix , or superficial transitional cell carcinoma of the bladder), which could affect the diagnosis or assessment of current condition.
* Patient is a pregnant or lactating woman
D: Inclusion Criteria:

* Age 20 to 80
* Hematopoietic WBC ≥ 4,000/mm\^3 Platelet ≥ 100,000/mm\^3
* Hepatic AST and ALT ≤ 2.5 times upper limit of normal(ULN) Total bilirubin ≤ 1.5 mg/dL
* Renal Creatinine ≤ULN

Exclusion Criteria:

* Prior anticancer treatment

Answer: B