Cetuximab and/or Bevacizumab Combined With Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Biological: bevacizumabBiological: cetuximabDrug: FOLFOX orDrug: FOLFIRI
- Registration Number
- NCT00265850
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
PURPOSE: This randomized phase III trial is studying cetuximab and/or bevacizumab when given together with combination chemotherapy to compare how well they work in treating patients with metastatic colorectal cancer.
RATIONALE: Monoclonal antibodies, such as cetuximab and 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. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, leucovorin, oxaliplatin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibodies together with combination chemotherapy may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective with cetuximab and/or bevacizumab in treating patients with colorectal cancer.
- Detailed Description
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to physician-selected chemotherapy (FOLFOX or FOLFIRI), prior adjuvant chemotherapy (yes vs no), and prior pelvic radiotherapy (yes vs no). Patients were randomized to 1 of 3 treatment arms.
Primary Objective:
* To determine if the addition of cetuximab to FOLFIRI or FOLFOX chemotherapy prolongs survival compared to FOLFIRI or FOLFOX with bevacizumab in patients with untreated, advanced or metastatic colorectal cancer who have K-ras wild type tumors.
Secondary Objectives:
* To evaluate response, progression-free survival (PFS), time to treatment failure (TTF), and duration of response (DR) among patients with unresectable advanced metastatic colon cancer treated with bevacizumab or cetuximab in addition to chemotherapy with FOLFIRI or FOLFOX
* To evaluate toxicity and, in particular, 60-day mortality among patients with unresectable advanced metastatic colon cancer treated with bevacizumab or cetuximab in addition to chemotherapy with FOLFIRI or FOLFOX
* To describe patients with unresectable locally advanced or metastatic colorectal cancer rendered "resectable" with chemotherapy
There are premedication guidelines that were established for patients assigned to receive cetuximab. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent an infusion or hypersensitivity reaction. Premedication is also recommended prior to subsequent doses, but at the investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Pretreatment with acetaminophen may also be used.
There are bevacizumab administration instructions for patients for whom surgery is being contemplated or required. For patients for whom elective surgery is contemplated, bevacizumab is to be discontinued for at least 8 weeks prior to surgery. Bevacizumab may be resumed after at least 4 weeks following surgery. Patients who undergo complete resection of metastatic disease will discontinue protocol therapy and may receive further treatment at the treating physician's discretion. For patients for whom non-elective surgery is required, hold bevacizumab as long as possible prior to surgery and for at least 6 weeks following surgery.
Patients received a minimum of two cycles of therapy. Patients were allowed to receive ancillary therapy per protocol. Treatment continued until disease progression, unacceptable toxicity, or surgery with curative intent as planned. After completion of study treatment, patients are followed up to 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2334
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: FOLFOX or FOLFIRI + cetuximab FOLFOX or Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm B: FOLFOX or FOLFIRI + cetuximab FOLFIRI Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm A: FOLFOX or FOLFIRI + bevacizumab FOLFIRI Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm C: FOLFOX or FOLFIRI + cetuximab + bevacizumab FOLFOX or Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm A: FOLFOX or FOLFIRI + bevacizumab bevacizumab Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm A: FOLFOX or FOLFIRI + bevacizumab FOLFOX or Patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm B: FOLFOX or FOLFIRI + cetuximab cetuximab Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Patients also receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm C: FOLFOX or FOLFIRI + cetuximab + bevacizumab bevacizumab Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm C: FOLFOX or FOLFIRI + cetuximab + bevacizumab cetuximab Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned. Arm C: FOLFOX or FOLFIRI + cetuximab + bevacizumab FOLFIRI Patients receive cetuximab 400mg/m\^2 IV over 2 hours on the first day of treatment, then 250 mg/m\^2 IV over 1 hour weekly thereafter. Also, patients receive bevacizumab 5 mg/kg IV every two weeks and then receive either FOLFOX or FOLFIRI every two weeks as described in the intervention section. One cycle is defined as 8 weeks of treatment. Treatment continues until disease progression, unacceptable toxicity or surgery with curative intent as planned.
- Primary Outcome Measures
Name Time Method Overall Survival Up to 5 years post-treatment Survival time will be defined as the time from registration to death. Time to event distributions will be estimated using the Kaplan-Meier method. Overall Survival (OS) will be compared between Arm A and Arm B.
- Secondary Outcome Measures
Name Time Method Duration of Tumor Response Up to 5 years post-treatment Progression-free Survival (PFS) Up to 5 years post-treatment PFS will be measured from study entry until first documented progression or death from any cause. Time to event distributions will be estimated using the Kaplan-Meier method. PFS will be compared between Arm A and Arm B.
Time to Treatment Failure Up to 5 years post-treatment
Trial Locations
- Locations (680)
Providence Cancer Center at Providence Hospital
🇺🇸Mobile, Alabama, United States
Alaska Regional Hospital Cancer Center
🇺🇸Anchorage, Alaska, United States
Providence Cancer Center
🇺🇸Anchorage, Alaska, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸Fort Smith, Arkansas, United States
NEA Medical Center - Stadium Boulevard
🇺🇸Jonesboro, Arkansas, United States
Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
🇺🇸Burbank, California, United States
East Bay Radiation Oncology Center
🇺🇸Castro Valley, California, United States
Valley Medical Oncology Consultants - Castro Valley
🇺🇸Castro Valley, California, United States
North Bay Cancer Center
🇺🇸Fairfield, California, United States
Kaiser Permanente - Fremont
🇺🇸Fremont, California, United States
Scroll for more (670 remaining)Providence Cancer Center at Providence Hospital🇺🇸Mobile, Alabama, United States