To determine if sorafenib when added to chemotherapy will slow disease progression more than chemotherapy alone in patients previously untreated for metastatic colorectal cancer.

• Metastatic
• Colorectal Cancer

• Drug: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
  Subjects will receive oral Sorafenib 400 mg BID continuously and IV mFOLFOX6 (5-FU 400 mg/m2 bolus and 2400 mg/m2 for 46 hrs; levo-leucovorin 200 mg/m2; 85 mg/m2 oxaliplatin) every 14 days until progressive disease
• Drug: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
  Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m2 bolus and 2400 mg/m2 for 46 hrs; levo-leucovorin 200 mg/m2; 85 mg/m2 oxaliplatin) every 14 days until progressive disease

• Arm 1: Experimental
  Intervention: Drug: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
• Arm 2: Placebo Comparator
  Intervention: Drug: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

Inclusion Criteria:

• Histological confirmation of adenocarcinoma of the colon or rectum
• Tumor tissue sample available for KRAS mutation 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

Exclusion Criteria:

• 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