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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00865709
First received: February 2, 2009
Last updated: September 28, 2012
Last verified: September 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Metastatic Colorectal Cancer
 Drug: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
Drug: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin)
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2b, DB, Randomized Study Evaluating Efficacy & Safety of Sorafenib Compared With Placebo When Administered in Combination With Modified FOLFOX6 for the Treatment of Metastatic CRC Subjects Previously Untreated for Stage IV Disease

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Bayer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks. ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) [ Time Frame: From randomization of the first subject until 33 months later. ] [ Designated as safety issue: No ]
    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) [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks. ] [ Designated as safety issue: No ]
    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.

  • Tumor Response [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks. ] [ Designated as safety issue: No ]
    Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) 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, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.

  • Duration of Response [ Time Frame: From randomization of the first subject until 23 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 198
Study Start Date: March 2009
Estimated Study Completion Date: December 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6
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)
 Drug: 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)
Placebo Comparator: Matching placebo + mFOLFOX6
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
 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/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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00865709

  Show 116 Study Locations
Sponsors and Collaborators
Bayer
Onyx Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Click here and search for drug information provided by the FDA.  This link exits the ClinicalTrials.gov site
Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Therapeutic Area Head, Bayer Healthcare AG
ClinicalTrials.gov Identifier: NCT00865709     History of Changes
Other Study ID Numbers: 13162, 2008-005025-11
Study First Received: February 2, 2009
Results First Received: January 31, 2012
Last Updated: September 28, 2012
Health Authority: Belgium: Federal Agency for Medicines and Health Products
Spain: Agencia espanola de medicamentos y productos sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Romania: National Medicine Agency
Russia: Federal Service for Control of Healthcare and Social Development - Roszdravnadzor (Scientific Center for pharmaceuticals expertise)
United States: Food and Drug Administration

Keywords provided by Bayer:
Colorectal Cancer
Metastasis
Stage IV
Liver Metastasis

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Sorafenib
Leucovorin
 Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on May 16, 2013