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