Metastatic Colorectal Cancer

- Histological confirmation of adenocarcinoma of the colon or rectum
- Tumor tissue sample available for KRAS and BRAF assessment
- Measurable metastatic Stage IV disease including at least one measurable lesion that has not previously been radiated
- No prior chemotherapy for metastatic CRC
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Life expectancy of at least 12 weeks
- Adequate bone marrow, liver, and renal function; adequate clotting parameters

- Prior treatment with sorafenib
- Clinical or radiographic evidence of brain metastasis
- Major surgery, surgical biopsy, or significant traumatic injury within 28 days of randomization; evidence or history of bleeding diathesis or coagulopathy
- Red blood cell (RBC), white blood cell (WBC), or platelet transfusions and/or growth factor use within 28 days before randomization
- Adjuvant therapy for CRC (Stage I, II, or III) completed within 12 months before randomization
- Serious, non-healing wound, ulcer, or bone fracture; Grade 3 or 4 hemorrhage within 28 days before randomization
- Use of anticoagulation therapy (low dose anticoagulation therapy to mitigate risk of thrombosis due to placement of a semi-permanent central venous port for administration of chemotherapy is allowed. The use of coumadin and related compounds is excluded.)
- Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg on repeated measurement) despite optimal medical management
- Thrombolic, embolic, venous, or arterial events (eg, cerebrovascular accident, including transient ischemic attacks) within 6 months before randomization
- Active cardiac disease including:
 -- Congestive heart failure
 -- Unstable angina or myocardial infarction within the 6 months before randomization
 -- Cardiac ventricular arrhythmias requiring antiarrhythmic treatment
- Peripheral neuropathy > Grade 1 (CTCAE)
- Known HIV infection or chronic hepatitis B or C infection
- Any active infection >/= Grade 2 (CTCAE)
- Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results
- Use of any investigational drug within 28 days or 5 half-lives of that drug, whichever is longer, before randomization
- Subjects with metastatic CRC who are currently candidates for surgery with curative intent