Please select the eligibility criteria that correspond to the clinical trial below.
Title: Planning Treatment for Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial
Brief Summary: To evaluate the efficacy of maintenance therapies following completion of standard first-line chemotherapy in patients with locally advanced or metastatic HER-2 positive or HER-2 negative oesophago-gastric adenocarcinomas.


Options:
A: 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
B: Inclusion Criteria - All Patients

* Histologically verified inoperable locally advanced or metastatic adenocarcinoma of the oesophagus, oesophago-gastric junction, or stomach.
* Completion of 18 weeks of first-line chemotherapy with either CX/ CAPOX or FOLFOX (HER2 negative) or CX/ CF + trastuzumab (HER2 positive) for locally advanced / metastatic disease with \> stable disease on the end of treatment CT scan (HER2 positive patients must have received at least one cycle of trastuzumab alongside first line chemotherapy; patients receiving chemotherapy delivered on a 3-weekly basis eg CX/ CAPOX should have received 6 cycles and on a two weekly basis e.g. FOLFOX should have received 9 cycles).
* Disease which, following first-line chemotherapy, remains inoperable and unsuitable for definitive chemoradiotherapy.
* Able to proceed with maintenance treatment within 28 days of the last day of the last cycle of chemotherapy.
* Formalin fixed paraffin embedded (FFPE) blocks of diagnostic tissue available for biomarker analysis.
* Any prior chemotherapy or radiotherapy in the adjuvant setting must have been completed at least 6 months prior to the first occurrence of metastatic disease.
* No prior radiotherapy in the advanced disease setting. Patients receiving palliative radiotherapy to sites of disease that are not measurable may be eligible and should be discussed with the Chief Investigator.
* Male/female patients aged ≥18 years.
* WHO Performance status 0, 1 or 2.
* Patients should have a projected life expectancy of at least 3 months.
* Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5x109/l; white blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be post-transfusion).
* Adequate renal function: calculated creatinine clearance ≥50ml/minute.
* Adequate liver function: serum bilirubin ≤1.5x ULN; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤2.5 x ULN (5 × ULN is acceptable for ALT, AST and ALP if liver metastases are present).
* Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 7 months following the last dose of assigned study drug(s).
* Written informed consent must be obtained from the patient before any study-specific procedures are performed.

Exclusion Criteria - All Patients

* Concurrent enrolment in another clinical trial unless it is an observational (non-interventional) clinical study.
* Tumours of squamous histology.
* Documented brain metastases, central nervous system metastases or leptomeningeal disease.
* Patients who have not recovered from clinically significant effects of any prior surgery, radiotherapy or any other anti-neoplastic therapies. All toxicities must have resolved to grade 1 or less, with the exception of peripheral neuropathy which must be less than or equal to grade 2 according to NCI CTCAE version 4.0.
* Any major surgery within 4 weeks prior to the start of study treatment.
* Uncontrolled hypertension (systolic blood pressure \>180 mm Hg or diastolic blood pressure \>100 mm Hg).
* Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, symptomatic congestive heart failure, uncontrolled cardiac dysrhythmia, or myocardial infarction within the last 12 months. Patients with any prior history of clinically significant cardiac failure are excluded from study entry.
* History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
* Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication.
* Patients who are pregnant or lactating.
* Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis A or C virus, acute or chronic active hepatitis B infection.
* Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial.
* Any other malignancies within the last 3 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
* Treatment with another investigational agent within 30 days of commencing study treatment.

Additional Inclusion / Exclusion Criteria - HER-2 Negative Patients (Arm A)

* Patients must have histologically or cytologically confirmed HER-2 negative disease (HER-2 0-2 by IHC; note if ISH testing is performed this must not demonstrate evidence of gene amplification).
* Patients with known capecitabine intolerance are excluded. This includes patients with previous coronary artery spasm or chest pain deemed to be capecitabine-related.
* Patients with homozygous DPYD gene mutations are excluded. Patients with heterozygous DPYD gene mutations who have tolerated dose-reduced fluoropyrimidines during first-line chemotherapy as per local guidelines are eligible.
* Prior treatment with a PARP inhibitor is excluded (only applicable for A4 \& A5 patients).
* Any Grade 3 or 4 GI bleeding within 3 months prior to enrollment are excluded
* Any Grade 3 or 4 venous thromboembolic event (VTE) that is considered by the investigator to be life threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 3 months prior to randomization are excluded.
* History of GI perforation within 6 months of randomisation are excluded
* History of hepatic encephalopathy or cirrhosis (level Child-Pugh B or worse) are excluded
* Patients must have adequate coagulation function as defined by International Normalised Ratio (INR) ≤1.5 and a partial thromboplastin time/activated partial thromboplastin time (PTT or aPTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy. Patients receiving warfarin must be switched to low molecular weight heparin prior to randomisation.
* Patients with a serious or non-healing wound, ulcer or bone fracture within 28 days prior to randomisation are excluded.
* The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (if urine dipstick is

  * 2+, a 24 hour urine collection for protein must demonstrate \< 1000mg of protein in 24 hours.
* Patients experiencing thromboembolic events, including but not limited to myocardial infarction, transient ischaemic attack, cerebrovascular accident, unstable angina, within 6 months prior to first dose of protocol therapy are excluded.
* Patients who have undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/ subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy are excluded.
* Patients receiving chronic anti-platelet therapy or NSAIDS including ibuprofen, naproxen, dipyridamole or clopidogrel, or similar agents are excluded. Once daily aspirin use (up to 325mg/day) is permitted.

Additional Inclusion / Exclusion Criteria - HER-2 Positive Patients (Arm B)

* Patients must have histologically or cytologically confirmed HER-2 positive disease (HER-2 3+ by IHC or HER-2 2+ by IHC and HER-2 gene amplified by ISH).
* Patients must have left ventricular ejection fraction (LVEF) \>50% as measured by echocardiogram or \>45% measured by MUGA (must also be greater than lower limit of normal at institution).
* Patients with active or prior history of New York Heart Association (NYHA) congestive heart failure are excluded.
* Patients with a known history of hypersensitivity to trastuzumab or any of its components are excluded.
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