Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study of Weekly Paclitaxel With or Without Ramucirumab (IMC-1121B) Drug Product in Patients With Metastatic Gastric Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine
Brief Summary: This is a Phase III randomized multicenter double-blind, placebo controlled trial evaluating the safety and efficacy of paclitaxel plus ramucirumab (IMC-1211B) drug product (DP) compared to paclitaxel plus placebo.


Options:
A: Inclusion Criteria:

* Histologically proven in operable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapse gastric adenocarcinoma
* Subjects must be able to take orally
* Measurable lesion and/or non-measurable lesion defined by RECIST
* ECOG performance status ≦ 1
* Hgb ≧ 8g/dL, WBC 4000-12000/mm3, platelets ≧ 100,000/mm3
* Creatine ≦ upper normal limit (UNL)
* Total bilirubin ≦ 1.5 X UNL
* AST, ALT and ALP ≦ 2.5 x UNL
* No prior chemotherapy
* Life expectancy estimated than 3 months
* Written informed consent

Exclusion Criteria:

* Active double cancer
* Gastrointestinal bleeding
* Excessive amounts of ascites require drainage
* Known brain metastases
* Symptomatic peripheral neuropathy ≧ garde 2. by NCI-CTCAE ver.3.0
* Pulmonary fibrosis, Intestinal pneumonitis
* History of hypersensitivity to fluoropyrimidines, docetaxel or medications formulated with polysorbate 80
* Any previous chemotherapy or radiotherapy for AGC
* Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant
* Treatment with any investigational product during the last 4 weeks prior to study entry
* Definite contraindications for the use of corticosteroids
* Any subject judged by the investigator to be unfit for any reason to participate in the study
B: Inclusion Criteria:

* Signed informed consent
* histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma
* Metastatic disease or locally advanced, unresectable disease
* Disease progression during or within 4 months after the last dose of the first-line therapy (platinum/fluoropyrimidine doublet with or without anthracycline)
* Organs are functioning well (liver, kidney, blood)
* Good performance status Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1

Exclusion Criteria:

* First line chemotherapy for metastatic gastric cancer other than platinum/fluoropyrimidine doublet with or without anthracycline
* Previous systemic therapy with other anti-angiogenic drugs
* Uncontrolled high blood pressure
* Symptomatic or poorly controlled heart disease or had a heart attack or stroke within the last 6 month
* Evidence of central nervous system (CNS) metastasis at baseline
C: Inclusion Criteria:

* Histologically or cytologically-confirmed diagnosis of tumor that is recurrent, metastatic, or persistent:

  * For Cohort A - triple negative breast cancer (estrogen, progesterone, and human epidermal growth factor receptor 2 \[HER2\] negative)
  * For Cohort B - squamous cell carcinoma of the head and neck (including human papilloma virus (HPV)-positive head and neck squamous cell cancer).
  * For Cohort C - urothelial tract cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell or non-transitional cell histology)
  * For Cohort D - adenocarcinoma of the stomach or gastroesophageal junction
  * For Cohort B2 - squamous cell carcinoma of the head and neck (both HPV-positive and -negative head and neck squamous cell cancer)
* Any number of prior treatment regimens
* Measurable disease
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
* Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
* Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study treatment

Exclusion Criteria:

* Currently participating in/has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
* Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Anti-cancer monoclonal antibody treatment within 4 weeks prior to study Day 1 or not recovered from adverse events due to agents administered more than 4 weeks earlier
* Chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
* Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents
* Evidence of interstitial lung disease
* Active infection requiring systemic therapy
* Known psychiatric or substance abuse disorders
* Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
* Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
* Known history of human immunodeficiency virus (HIV)
* Known active Hepatitis B or Hepatitis C
* Received live vaccine within 30 days prior to start of study treatment
* Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is Investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by Chair or Designee) is given allowing exception to this criterion for a specific participant
D: Inclusion Criteria:

* Ambulatory patients
* Karnofsky performance status of ≥70 %.
* Histologically confirmed gastric adenocarcinoma, staged pathologically, stage II (T2N1, T1N2, T3N0), IIIa (T3N1, T2N2, T4N0), and IIIb (T3N2). At least 15 examined lymph nodes are required to ensure the adequate TNM (Tumor Nodes Metastases classification.
* Patients who underwent curative D2 lymphadenectomy resection for gastric cancer with no macroscopic or microscopic evidence for remaining tumor, who can be randomized to either study arm within 6 weeks after surgery.

Exclusion Criteria:

* Pregnant or lactating women.
* Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-child bearing potential.
* Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
* Any evidence of metastatic disease (including presence of tumor cells in the ascites).
* Previous cytotoxic chemotherapy, radiotherapy or immunotherapy except corticosteroids, for the currently treated gastric cancer.
* Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery.
* History of another malignancy within the last five years except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix.
* Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication or myocardial infarction within the last 12 months.
* Lack of physical integrity of the upper gastrointestinal tract or those who have malabsorption syndrome likely to influence absorption of capecitabine, or inability to take oral medication.
* Known peripheral neuropathy ≥ CTCAEv3 grade 1 (Common Terminology for Adverse Events). Absence of deep tendon reflexes as the sole neurologic abnormality does not render the patient ineligible.
* Organ allografts requiring immunosuppressive therapy.
* Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease.
* Moderate or severe renal impairment \[creatinine clearance equal to or below 50 ml/min (calculated according to Cockroft and Gault)\], or serum creatinine \> 1.5 x upper limit of normal (ULN).
* Any of the following laboratory values:

  * Absolute neutrophil count (ANC) \< 1.5 x 109/L
  * Platelet count \< 100 x 109/L
  * Total bilirubin \> 1.5 x ULN
  * ALAT, ASAT \> 2.5 x ULN
  * Alkaline phosphatase \> 2.5 x ULN.
* Prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented dihydropyrimidine dehydrogenase (DPD) deficiency) or patients with known DPD deficiency.
* Hypersensitivity to platinum compounds or any of the components of the study medications.
* Received any investigational drug or agent/procedure, i.e. participation in another trial, within 4 weeks before randomization.
* Blood transfusions or growth factors to aid hematologic recovery within 2 weeks prior to study treatment start.
* Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Answer: B