Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Placebo-controlled Phase II Trial Investigating SUNITINIB Versus Placebo in Patients With Chemorefractory Advanced Adenocarcinoma of the Stomach or Lower Esophagus Treated With Chemotherapy FOLFIRI
Brief Summary: This trial will be conducted to evaluate the efficacy, safety and tolerability of SUNITINIB as add-on therapy with a widely used second-line palliative FOLFIRI chemotherapy in patients with chemo-refractory advanced or metastatic adenocarcinoma of stomach or lower esophagus (mGC).

There is a clear scientific rationale for the use of Sunitinib to treat patients with mGC. Despite recent therapeutic advances, the median overall survival (OS) in patients with mG is still ≤ 12 months. Therefore, newer agents with novel mechanisms of action are desperately needed for treatment of these patients.


Options:
A: Inclusion Criteria:

* Written informed consent obtained prior to any study specific procedures.
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Life expectancy of at least 3 months.
* Able to comply with the protocol.
* Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable, locally advanced, or metastatic disease, not amenable to curative therapy.
* Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST).
* Patient not receiving anticoagulant medication must have an International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x Upper Limit of Normal (ULN) within 7 days prior to randomisation.

Exclusion Criteria:

* Previous chemotherapy for locally advanced or metastatic gastric cancer. Patients may have received prior neoadjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to randomisation.
* Previous platinum or anti-angiogenic therapy (ie, anti-vascular endothelial growth factor \[VEGF\] or VEGF receptor tyrosine kinase inhibitor, etc.).
* Patients with locally advanced disease who are candidates for curative therapy (including operation and/or chemotherapy and/or radiotherapy).
* Radiotherapy within 28 days of randomisation.
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomisation, or anticipation of the need for major surgery during the course of the study treatment (planned elective surgery).
* Minor surgical procedures within 2 days prior to randomisation.
* Evidence of central nervous system (CNS) metastasis at baseline.
* History or evidence upon physical/neurological examination of CNS disease unrelated to cancer unless adequately treated with standard medical therapy, eg, uncontrolled seizures.
* History of another malignancy which could affect compliance with the protocol or interpretation of results.
* Inadequate bone marrow function.
* Inadequate liver function.
* Inadequate renal function.
* Uncontrolled hypertension or clinically significant (ie, active) cardiovascular disease.
* Active infection requiring intravenous antibiotics at randomisation.
* History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
* Serious or non-healing wound, peptic ulcer, or (incompletely healed) bone fracture.
* Active gastrointestinal bleeding.
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of randomisation.
* Neuropathy (eg, impairment of hearing and balance) ≥ grade II according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
* Chronic daily treatment with aspirin or clopidogrel.
* Chronic daily treatment with oral corticosteroids; inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed.
* Known hypersensitivity to any of the study drugs or excipients or to Chinese hamster ovary cell products or to other recombinant human or humanised antibodies.
* Known dihydropyrimidine dehydrogenase (DPD) deficiency.
* Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or that may affect patient compliance with the study, or place the patient at high risk from treatment complications.
* Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
* Pregnant or lactating females.
* Women of childbearing potential not using effective nonhormonal (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) means of contraception.
* Sexually active men unwilling to practice contraception during the study.
* Current or recent (within the 28 days prior to randomisation) treatment with another investigational drug or participation in another investigational study.
B: 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
C: Inclusion Criteria:

* Male or female patients \> 18 years old
* Histologically or cytologically confirmed and documented gastric adenocarcinoma
* Documented progression after 1 or 2 prior chemotherapy treatments for advanced disease
* ECOG Performance Status of \< 2
* Lab parameters within specifically defined intervals
* Able to provide written informed consent

Exclusion Criteria:

* Patients who have received \> 2 prior systemic therapies for advanced disease
* Administration of another anticancer therapy within 3 weeks prior to randomization
* Chronic treatment with steroids or another immunosuppressive agent
* Major surgery within 2 weeks prior to randomization
* Patients with CNS metastases
* Any other severe and/or uncontrolled medical condition

Other protocol-defined inclusion/exclusion criteria may apply
D: 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

Answer: B