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:

* Advanced gastric cancer (including GEJ) that has progressed following first-line therapy.
* Patients must be ≥18 years of age. Age ≥20 if Japanese
* Provision of tumour sample (from either a resection or biopsy).
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline and following up visits.

Exclusion Criteria:

* More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
* Any previous treatment with a Polyadenosine 5'-diphosphoribose \[poly-(ADP-ribose)\] polymerisation (PARP) inhibitor, including olaparib.
* Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥5 years.
* Human Epidermalgrowth Factor Receptor-2 (HER2) positive patients.
B: Inclusion Criteria:

1. Has histologically confirmed non-resectable, metastatic gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction.
2. Has previously received at least 2 prior regimens for advanced disease and were refractory to or unable to tolerate their last prior therapy.
3. Has measureable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
4. Is able to take medications orally (ie, no feeding tube).
5. Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
6. Has adequate organ function as defined by protocol defined labs.
7. Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

Exclusion Criteria:

1. Has certain serious illnesses or medical conditions
2. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent within the specified time frames prior to study drug administration.
3. Has previously received TAS-102.
4. Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events Grade 2 attributed to any prior therapies.
5. Is a pregnant or lactating female.
C: Inclusion Criteria:

* Male or female subjects aged greater than or equal to (\>=) 18 years
* Subjects with histologically confirmed recurrent unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
* Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor tissue
* Subjects must have received 2 prior courses of systemic treatment for unresectable, recurrent, locally advanced or metastatic gastric cancer, and must have progressed after the second line
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial entry
* Adequate hematological, hepatic and renal functions defined by the protocol
* Negative blood pregnancy test at Screening for women of childbearing potential.
* Highly effective contraception for both male and female subjects if the risk of conception exists

Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
* Concurrent anticancer treatment
* Major surgery
* Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to less than \[\<\] 10 mg prednisone daily).
* All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder,cervical, colorectal, breast)
* Prior organ transplantation, including allogeneic stem-cell transplantation Significant acute or chronic infections
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
* Persisting toxicity of grade \>2 related to prior therapy except neuropathy and alopecia
* Neuropathy Grade greater than or equal (\>=) 3.
* Pregnancy or lactation
* Known alcohol or drug abuse
* History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
* Clinically significant (i.e., active) cardiovascular disease
* All other significant diseases might impair the subject's tolerance of trial treatment
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
* Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
* Legal incapacity or limited legal capacity
* Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsistent with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization
* Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call
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: D