Study of Modified FOLFOX6 Plus or Minus Sorafenib in Stage IV Metastatic Colorectal Carcinoma (mCRC) Subjects

Phase 2

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin); Drug: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)

• Registration Number: NCT00865709
• Lead Sponsor: Bayer

Brief 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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2009-02-02
• Study Start: 2009-03
• Study First Submitted QC: 2009-03-18
• Study First Posted: 2009-03-19
• Primary Completion: 2011-01
• Results First Submitted: 2012-01-31
• Study Completion: 2012-02
• Results First Submitted QC: 2012-02-15
• Results First Posted: 2012-03-20
• Status Verified: 2014-11
• Last Update Submitted: 2014-11-25
• Last Update Posted: 2014-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 198

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6	Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)	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)
Matching placebo + mFOLFOX6	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/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

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	From randomization of the first subject until 23 months later, assessed every 8 weeks.	Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression or death due to any cause, whichever occurred first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization of the first subject until 33 months later.	Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time to Progression (TTP)	From randomization of the first subject until 23 months later, assessed every 8 weeks.	Time to progression (TTP) was defined as the time from date of randomization to disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Duration of Response	From randomization of the first subject until 23 months later, assessed every 8 weeks	Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) was first documented or to the date of death, whichever occurred first according to Response Evaluation Criteria in Solid Tumors (RECIST). Subjects still having CR or PR and alive at the time of analysis were censored at their last date of tumor evaluation. CR was defined as disappearance of tumor lesions, PR as a decrease of at least 30% and PD as an increase of at least 20% in the sum of tumor lesions sizes.
Overall Response	From randomization of the first subject until 23 months later, assessed every 8 weeks.	Overall response of a subject was defined as the best tumor response (Complete Response (CR) or Partial Response (PR)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.