FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric Cancer

Inclusion Criteria:

Confirmed adenocarcinoma of esophagus, GE junction or gastric origin
Disease is not amenable to curative resection and is unresectable, locally advanced or metastatic
Have not received any prior chemotherapy, investigative or biologic agents for esophagogastric cancer except in the neoadjuvant or adjuvant setting
Any major surgery must be completed at least 4 weeks prior to study entry, minor procedures must be completed at least 2 weeks prior to study entry
Vascular access device insertion should be performed at least 1 week prior to study entry. A central line is recommended for all participants
Willing to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after the last dose of Ziv-aflibercept/placebo

Exclusion Criteria:

History of hypertension unless adequately controlled
Evidence of active bleeding from primary tumor at time of study entry
Pregnant or breastfeeding
Squamous cell carcinoma histology
Prior treatment for advanced or metastatic disease
Palliative radiation to < 25% of bone marrow must have been completed 2 weeks prior to study entry, palliative RT to > 25% must have been completed 4 weeks prior to study entry
Known allergy to study agents
Known dihydropyrimidine dehydrogenase deficiency or thymidylate kinase gene polymorphism predisposing participant to 5-FU toxicity
History of symptomatic congestive heart failure
Clinically significant peripheral arterial disease
Grade 2 or higher sensory or motor neuropathy
Serious unhealed wound, ulcers or bone fractures
History of HIV positivity or hepatitis B or C
History of abdominal fistula, wound dehiscence, GI perforation, intra abdominal abscess, uncontrolled GI bleeding or diverticulitis that required hospitalization within 6 months of study entry
History of arterial thrombotic events
History of CNS hemorrhage in past 6 months
Use of warfarin
History of prior or synchronous malignancy except if treated with curative intent more than 3 years prior to enrollment, or adequately treated non-melanoma skin cancers, cervical carcinoma in situ or prostatic intraepithelial neoplasia without evidence of prostate cancer
Uncontrolled non-malignant illness
Uncontrolled psychiatric illness