Study of Modified FOLFOX6 Plus or Minus Sorafenib in Stage IV Metastatic Colorectal Carcinoma (mCRC) Subjects
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin); Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Intervention description: Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD); Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease
Intervention MeSH terms: Leucovorin; Oxaliplatin; Fluorouracil; Sorafenib; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 198.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; Metastasis; Stage IV; Liver Metastasis

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  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

        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