Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colon Cancer That Cannot Be Removed By Surgery
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colon cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colon cancer that cannot be removed by surgery.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and a Synchronous Asymptomatic Primary Tumor|
- Major Morbidity Related to the Intact Primary Tumor [ Time Frame: 24 months ] [ Designated as safety issue: No ]Cumulative incidence was used to compute percent probability of morbidity. Cumulative incidence at time t measures the probability of a participant having an event (i.e., Colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death) over the given duration, t. It involves computing the probability of an event at any observed time (i.e., the number of new cases during a period divided by the number of subjects at risk) and multiplying these successive probabilities by any early computed probability to get the final estimate.
- Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration [ Time Frame: Time from start of study through year 5 ] [ Designated as safety issue: No ]
- Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery [ Time Frame: Time from start of study through year 5 ] [ Designated as safety issue: No ]
- Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery [ Time Frame: Time from start of study through year 5 ] [ Designated as safety issue: No ]
- Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery [ Time Frame: Time from start of study through year 5 ] [ Designated as safety issue: No ]
- Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0 [ Time Frame: Time from start of study through year 5 ] [ Designated as safety issue: Yes ]
- Overall Survival as Measured by Death From Any Cause [ Time Frame: Time from start of study through year 5 ] [ Designated as safety issue: No ]
|Study Start Date:||March 2006|
|Study Completion Date:||December 2012|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Experimental: Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
bevacizumab 5 mg/kg IV on day 1 every 14 days until excessive toxicity or disease progressionDrug: fluorouracil
5-FU 400 mg/m2 IV bolus over 2-4 minutes then 2400 mg/m2 IV continuous infusion over 46 hours on day 1 every 14 days until excessive toxicity or disease progression
Other Name: 5-FUDrug: leucovorin
leucovorin 400 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression
Other Name: leucovorin calciumDrug: oxaliplatin
Oxaliplatin 85 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression
- Determine the rate of major morbidity in patients with unresectable stage IV colon cancer and a synchronous asymptomatic primary tumor treated with fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX6) in combination with bevacizumab without resection of the primary tumor.
- Determine the rate of specific events related to the intact primary tumor requiring hospitalization or a major intervention but not requiring surgery.
- Determine the rate of ≥ grade 3 toxicity as defined by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) that is related to study therapy prior to disease progression.
- Determine overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV given concurrently with leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 5 years after study entry.
PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00321828
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|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation Inc|