Combination Chemotherapy for the Treatment of Metastatic or Unresectable Gastroesophageal Cancers, SAGE Trial

Inclusion Criteria

• Histologically and/or cytologically confirmed diagnosis of metastatic or unresectable adenocarcinoma of stomach, gastroesophageal junction or esophagus
• Eastern Cooperative Oncology Group (ECOG) performance status of performance status (PS) 0-2
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• No prior systemic therapy for the present cancer given in the metastatic setting and > 6 months from administration of peri-operative chemotherapy, if applicable * Note: up to two prior cycles of leucovorin, infusional fluorouracil and oxaliplatin (mFOLFOX6) for the present illness is permitted if patients otherwise qualify for the study with adequate baseline imaging * Patients who have received radiosensitizing doses of carboplatin/cisplatin and/or paclitaxel (or equivalent) with a course of radiotherapy will be eligible
• At least 18 years of age
• Absolute neutrophil count >= 1500 cells/uL
• Hemoglobin >= 8 g/dL
• Platelets > 100,000/uL
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 30 mL/min by Cockroft-Gault
• Total bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x ULN, unless with liver metastases and then must be < 5 x ULN of normal
• Women and men of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect pregnancy on study, she must notify her treating physician immediately
• Ability to understand the nature of this study protocol and give written informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria

• Receipt of any investigational agents at the time of registration
• Known, untreated brain metastases
• Grade 2 or greater peripheral neuropathy
• Presence of any additional active malignancy within the past 3 years where the malignancy is at least reasonably likely to alter the course of therapy, require systemic therapy or interfere with imaging assessments
• For those patients who are going to receive a PD-1 inhibitor: * No active use of systemic corticosteroids at the time of enrollment, at a dose equivalent of 10 mg/day or prednisone * Clinically significant autoimmune disease which is active or has required systemic immunosuppression within the last 2 years * Prior organ transplant or bone marrow transplant * History of interstitial lung disease or pneumonitis
• Uncontrolled intercurrent illness, including significant active infection, symptomatic congestive heart failure, unstable angina or active arrhythmia
• Major surgery within the 4 weeks prior to initiation of study treatment (diagnostic laparoscopy is not considered a major surgery for these purposes)
• A history of allergy or hypersensitivity to any of the study drugs
• Any additional significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from fully participating in the study