Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase II/III Trial of Second Line Chemotherapy Comparing CPT-11 Monotherapy Versus S-1/CPT-11 Combination for S-1 Refractory Gastric Cancer
Brief Summary: The purpose of this study is compare overall survival of the test arm (CPT-11/S-1 combination) to the control arm (CPT-11 alone) in the subjects with S-1 refractory advanced gastric cancer.


Options:
A: Inclusion Criteria:

* Histologically proven inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) or relapse gastric adenocarcinoma
* Subjects must be able to take orally
* Subjects must be confirmed to be PD status by picture diagnosis after first-line chemotherapy using S-1 alone, S-1 + Cisplatinum or S-1 + taxane, except S-1 + CPT-11
* Within 4 weeks from the diagnosis of PD
* Total dosage of S-1 at the first-line is over 2,240mg/m2 in S-1 alone treatment, 1,680mg/m2 in the S-1 combination
* ECOG performance status ≤ 1
* Follow up Age 20 or over
* Life expectancy estimated more than 12 weeks
* Hgb ≥ 8 g/dL, WBC 4,000-12,000/mm3, ANC ≥ 2,000/mm3, platelets ≥ 100,000/mm3
* Creatinine ≤ upper normal limit (UNL)
* Total bilirubin ≤ 1.5 X UNL
* Written informed consent

Exclusion Criteria:

* S-1 + CPT-11 was employed as a first-line
* Any other cytotoxic agents therapy, immuno-therapy, radiation-therapy
* After S-1 adjuvant
* Suspended cases by adverse events by S-1 or S-1 combination
* Excessive amounts of ascites require drainage
* Known brain metastases
* History of hypersensitivity to fluoropyrimidines and CPT-11
* Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant
* Active double cancer
* Gastrointestinal bleeding
* Any subject judged by the investigator to be unfit for any reason to participate in the study
B: Inclusion Criteria:

* metastatic or locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
* no prior chemotherapy in metastatic state
* adequate blood and biochemistry parameters

Exclusion Criteria:

* hypersensitivity for 5-FU, Leucovorin, Oxaliplatin or Docetaxel
* KHK, cardiomyopathy or cardiac insufficiency
* malignancy \<5 years ago
* brain metastases
* severe internal disease or inadequate blood and biochemistry parameters
C: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of at least 12 weeks from the first dose of study treatment
* Measurable and/or evaluable disease based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
* Adequate organ function as determined by the following laboratory results, within 28 days prior to randomization
* Participants must have a history of advanced gastric cancer (AGC), defined as unresectable and locally advanced or metastatic gastric cancer, including adenocarcinoma of the gastroesophageal junction (GEJ), and must have experienced disease progression during or after first-line therapy for their disease
* HER2-positive tumor (primary tumor or metastatic lesion) as confirmed by central laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
* Participants must have received at least one prior chemotherapy regimen for AGC; prior therapy does not need to have included HER2-directed therapy.
* First-line therapy for AGC, including adenocarcinoma of the GEJ, must have included a combination of at least a platinum- and a fluoropyrimidine-based treatment given concurrently; prior therapy does not need to have included a HER2-directed therapy.
* Adjuvant or neoadjuvant therapy for AGC is allowed.

Exclusion Criteria:

* An interval shorter than 21 days from the last dose of chemotherapy or HER2-directed therapy until the time of randomization
* Prior treatment with trastuzumab emtansine, docetaxel, or paclitaxel either as single agents or as part of a treatment regimen.
* Treatment with any investigational anticancer drug within 21 days of the first study treatment administration
* More than one prior line of therapy for advanced gastric cancer
* History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
* Brain metastases that are untreated or symptomatic or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within 1 month of randomization
* Peripheral neuropathy Grade \>/=2
* Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, serious cardiac arrhythmia)
* Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)
* Clinically significant bleeding within 30 days before enrollment
* For female participants, current pregnancy or lactation
* Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
* Infection with Human immunodeficiency virus (HIV) or hepatitis B virus, hepatitis C virus
D: Inclusion Criteria:

* Signed and dated informed consent before the start of specific protocol procedures
* Histological proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction or lower esophagus
* Failure of any prior chemotherapy (docetaxel and/or platinum-based chemotherapy); but patient has not previously received FOLFIRI treatment
* Measurable metastatic disease according to the RECIST criteria patients aged 18 years and older
* karnofsky index 100 - 70 %
* Life expectancy \> 12 weeks
* Adequate hematological, hepatic and renal functions
* At least 3 weeks from previous docetaxel- and/or platinum-based chemotherapy
* Recovery from hematological side effects (CTC grade \<1) and non-hematological side effects (CTC grade=\<1) of any prior therapy (except oxaliplatine induced neuropathy CTC grade =\<2)

Exclusion Criteria:

* History of another primary malignancy \>3 years, with the exception of non-melanoma skin cancer and in situ carcinoma of the uterine cervix
* Any prior palliative radiotherapy of the target lesions
* Concurrent treatment with any other medicinal anti-cancer therapy
* Prior treatment with a VEGF, VEGFR or RTK inhibitor, or prior enrolment on this study
* Known allergic/hypersensitivity reaction to any of the components of the treatment
* Treatment with potent CYP3A4 inhibitor within 7 days of Sunitinib/placebo dosing or with potent CYP3A4 inducer within 12 days of Sunitinib/placebo dosing
* Other serious illness or medical conditions within the last 12 months prior to study drug administration: Unstable cardiac disease despite treatment; myocardial infarction within 12 months prior to study entry; congestive heart failure NYHA grade 3 and 4; Hypertension that cannot be controlled by medication ; ongoing cardiac dysrhythmias of NCI CTCAE grade \>2, atrial fibrillation of any grade, or QTc interval \>450 msec for males or \>470 msec for females; History of significant neurologic or psychiatric disorders including dementia or seizures; Active uncontrolled infection; History of clinically significant bleeding within the past 6 months, including hemoptysis or haematuria, or underlying coagulopathy; Active disseminated intravascular coagulation; Cerebrovascular accident including transient ischemic attack; Pulmonary embolus; Bowel obstruction or chronic diarrhoea, history or presence of inflammatory enteropathy or extensive intestinal resection; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment, unless affected area has been removed surgically
* Known deficit in DPD
* Hypercalcemia not controlled by bisphosphonates
* Contraindications to the use of atropine
* Pregnant or lactating women; female patients who are pregnant or lactating or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 3 months after discontinuing study treatment
* Known drug abuse/alcohol abuse
* Current, recent, or planned participation in an experimental treatment drug study other than this protocol
* Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks before starting treatment; anticipation of need for major surgical procedure (e.g. impending bowel obstruction) during the course of the study
* History of other medical or psychiatric condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications

Answer: A