A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy

Inclusion Criteria

• Documented diagnosis of metastatic colorectal cancer
• One measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• No prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil containing adjuvant therapy in previous 6 months
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

Exclusion Criteria

• Any prior Vascular Endothelial Growth Factor (VEGF)-directed therapy or any other agent or investigational agent targeting the VEGF pathway
• Primary Central Nervous System (CNS) malignancies or CNS metastases
• Hematologic abnormalities:
• Hemoglobin 1.5 X Upper Limit of Normal (ULN)
• Serum chemistry abnormalities:
• Total bilirubin > 1.5 X ULN,
• Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2.5 X ULN,
• Alkaline phosphatase > 2.5 X ULN,
• Serum albumin 1.5 X ULN,
• Proteinuria > 2+ by urine dipstick
• Significant cardiovascular disease
• Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
• Non-healing wound, bone fracture, or skin ulcer
• Inadequate recovery from any prior surgical procedure or major surgical procedure within 8 weeks prior to administration, or anticipation of major surgical procedure during the course of the study
• History of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks
• An active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
• Serious/active infection or infection requiring antibiotics
• Significant bleeding disorders within 6 months prior to administration of first dose of study drug
• Active second primary malignancy, other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subject is not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for > 5 years
• History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, history of Grade 3 hypersensitivity to oxaliplatin, history of allergic reaction to folic acid
• Female subject is pregnant or lactating
• Known history of genetic or acquired immune suppression disease including Human Immunodeficiency Virus (HIV); subjects on immune suppressive therapy for organ transplant
• Inability to swallow pills, malabsorption syndrome or gastrointestinal disease, major resection of the stomach or small bowel, or gastric bypass
• Uncontrolled neuro-psychiatric disorder or altered mental status
• Peripheral neuropathy ≥ Grade 2
• Participating in another interventional protocol