Study population
undifferentiated carcinoma, Interstitial lung disease, randomisationMain, gastro-oesophageal carcinoma, gastric or GOJ cancer, Adenocarcinoma
UNCONTROLLED HYPERTENSION, UNDIFFERENTIATED CARCINOMA, INTERSTITIAL LUNG DISEASE, ADVERSE EVENTS, DISEASE, EVALUABLE, METASTATIC DISEASE, ADENOCARCINOMA
INTEGRATE IIa and INTEGRATE IIb have similar eligibility criteria:Participants aged ≥ 18 years with ECOG performance status < 2, who have histological or cytological confirmation of metastatic or locally advanced gastro-oesophageal carcinoma (gastric or GOJ cancer). Participants must have failed or be intolerant to a minimum of 2 lines of prior anti-cancer therapy and must have had at least one platinum agent and one fluoropyrimidine analogue.Other main eligibility criteria include:1. Evaluable disease according to RECIST 1.12. Adenocarcinoma or undifferentiated carcinoma histology3. Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy will be considered as first line treatment if the patient has relapsed or progressed within 6 months of completing treatment4. Ramucirumab monotherapy or immunotherapy with a checkpoint inhibitor will be considered a line of treatment5. HER2 positive participants must have previously received trastuzumab6. Adequate organ function defined as below:i. Bone marrow: ANC (absolute neutrophil count) ≥ 1500/μl, platelets ≥ 100,000/μl, haemoglobin ≥ 9 g/dl. INR (international normalised ratio) and APTT (activated partial thromboplastin time) ≤ 1.5 × ULN (upper limit of normal). Note: participants previously on long-term anticoagulation with warfarin or low molecular weight heparin are eligible.ii. Adequate liver function: Total bilirubin ≤ 1.5 × ULN; AST (aspartate transaminase), ALT (alanine transaminase) and/or ALP (alkaline phosphatase) ≤ 5 × ULN.iii. Adequate renal function, creatinine clearance, as measured by the Cockcroft and Gault formula of > 50mls/minute.iv. Adequate cardiac function: left ventricular ejection fraction ≥ 50% (INTEGRATE IIa only).7. Study treatment to start within 7 days of randomisationMain exclusion criteria include:1. Poorly controlled hypertension (systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)2. Prior exposure to anti-VEGF targeted therapy using small molecule VEGF TKIs. Prior anti-VEGF targeted monoclonal antibody therapies such as bevacizumab and ramucirumab are permitted3. Any prior use of more than one immune checkpoint inhibitor (INTEGRATE IIb only)4. Palliative radiotherapy unless more than 14 days between completion of radiation and date of registration and adverse events resulting from radiation have resolved to less than grade 2 according to CTCAE V4.035. Interstitial lung disease with ongoing signs and symptoms6. Uncontrolled metastatic disease to central nervous system