Phase I/II Trial of Tivantinib With FOLFOX for the Treatment of Advanced Solid Tumors and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction or Stomach

Inclusion Criteria: * Life expectancy ≥12 weeks. * Karnofsky performance status ≥70% * Patients must have measurable disease per RECIST Version 1.1. * Adequate hematologic function defined as: * Absolute neutrophil count (ANC) ≥1500/μL * Hemoglobin (Hgb) ≥9 g/dL (5.6 mmol/L) * Platelets ≥100,000/uL * Adequate liver function defined as: * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST \<2.5 x the institutional upper limit of normal (ULN) or ≤5.0 x the institutional ULN in patients with liver metastases. * Total bilirubin within normal limits (WNL) (or ≤1.5 x the institutional ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin within normal limits in patients with well documented Gilbert Syndrome). * Serum creatinine \<1.5 X ULN or calculated 24-hour creatinine clearance \>40 mL/min. * Patients who are on coumadin should have an international normalized ratio (INR) value within the therapeutic range (i.e., 2 to 3 x ULN). Patients who are on stable, chronic doses of coumadin are eligible. PHASE I ONLY •Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard therapy would include FOLFOX or for which standard curative or palliative measures do not exist or are no longer effective. PHASE II ONLY * Histologic documentation of adenocarcinoma of the esophagus, GE junction, or stomach. * Metastatic GE cancer as documented by radiologic study or surgical evidence of metastatic disease. * No prior chemotherapy for metastatic disease. Previous combined modality therapy for locally advanced disease is allowed if completed ≥6 months prior to recurrence (acceptable chemotherapy drugs include 5-FU, capecitabine, cisplatin, carboplatin, paclitaxel, oxaliplatin, and docetaxel). * Prior radiation therapy is allowed. At least 4 weeks must have elapsed from completion of the radiation therapy and all signs of toxicity must have resolved. * Prior adjuvant chemotherapy is allowed if completed ≥6 months prior to the documentation of metastatic disease. Exclusion Criteria: * Patients with known central nervous system (CNS) metastases may be enrolled, provided the metastases have undergone treatment, the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases. * Patients with poorly controlled or clinically significant atherosclerotic vascular disease including New York Heart Association Grade 3 or greater congestive heart failure; unstable angina ; myocardial infarction, cardiovascular accident, transient ischemic accidents, angioplasty, cardiac or vascular stenting in the past 6 months; or ventricular arrhythmia requiring medication. Patients with previously diagnosed symptomatic bradycardia will be ineligible. * Medical history of prolonged QT syndrome (\>450 ms). * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements. * History of hypersensitivity to active or inactive excipients of any component of treatment (5-FU, leucovorin, oxaliplatin, or Tivantinib), or known dipyrimidine dehydrogenase deficiency. * Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). * Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) ≤6 months prior to Day 1 of treatment. * Any known positive test for human immunodeficiency virus, hepatitis C virus or acute or chronic hepatitis B infection. * Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study. * Use of any non-approved or investigational agent ≤28 days or 5 half-lives prior to administration of the first dose of study drug, whichever is shorter. * Patients may not receive any other investigational or anti-cancer treatments while participating in this study. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g. active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). * Inability to swallow whole capsules. PHASE I ONLY •Patients who have had radiation therapy, hormonal therapy, biologic therapy, investigational agents, or chemotherapy for cancer within 28 days or 5 half-lives of the chemotherapy or biologic/targeted agents, whichever is shorter, prior to Day 1 of the study. PHASE II ONLY •Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a disease free survival ≥5 years.