Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Biological: bevacizumab
- Registration Number
- NCT00098787
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, leucovorin, and fluorouracil, 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 colorectal cancer by blocking blood flow to the tumor. Giving bevacizumab together with combination chemotherapy may be a better way to block tumor growth. Studying the amount of an enzyme found in the tumor may help doctors plan the best treatment.
PURPOSE: This randomized phase II trial is studying giving bevacizumab, oxaliplatin, and irinotecan or giving bevacizumab, oxaliplatin, leucovorin, and fluorouracil in treating patients with metastatic or recurrent colorectal cancer.
- Detailed Description
OBJECTIVES:
* Compare the response rate (complete and partial), progression-free survival, and overall survival of patients with previously untreated metastatic or locally recurrent colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan, oxaliplatin, and bevacizumab.
* Compare the toxicity of these regimens in these patients.
* Correlate gene expression with response rates in patients treated with these regimens.
* Correlate gene expression with toxicity of these regimens in these patients.
* Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian excision repair cross complementary protein expression with antitumor response in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with high TS expression are randomized to 1 of 2 treatment arms (Arms A or B). Patients with low or indeterminate TS expression are assigned to Arm C.
* Arm A: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15.
* Arm B: Patients receive bevacizumab and oxaliplatin as in arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15.
* Arm C: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil as in arm B.
In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from the date of study registration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 247
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (High TS, IROX/bev) bevacizumab Patients with high TS who are randomized to Arm A receive irinotecan and oxaliplatin plus bevacizumab (IROX/bev). The combination regimen is administered by giving bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met. Arm B (High TS, FOLFOX/bev) leucovorin calcium Patients with high TS who are randomized to Arm B receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev). The combination regimen is administered by giving bevacizumab and oxaliplatin as in Arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met. Arm C (Low or intermediate TS, FOLFOX/bev) bevacizumab Patients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B. Arm C (Low or intermediate TS, FOLFOX/bev) leucovorin calcium Patients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B. Arm B (High TS, FOLFOX/bev) bevacizumab Patients with high TS who are randomized to Arm B receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev). The combination regimen is administered by giving bevacizumab and oxaliplatin as in Arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met. Arm A (High TS, IROX/bev) irinotecan hydrochloride Patients with high TS who are randomized to Arm A receive irinotecan and oxaliplatin plus bevacizumab (IROX/bev). The combination regimen is administered by giving bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met. Arm A (High TS, IROX/bev) Oxaliplatin Patients with high TS who are randomized to Arm A receive irinotecan and oxaliplatin plus bevacizumab (IROX/bev). The combination regimen is administered by giving bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met. Arm C (Low or intermediate TS, FOLFOX/bev) Oxaliplatin Patients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B. Arm B (High TS, FOLFOX/bev) fluorouracil Patients with high TS who are randomized to Arm B receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev). The combination regimen is administered by giving bevacizumab and oxaliplatin as in Arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met. Arm C (Low or intermediate TS, FOLFOX/bev) fluorouracil Patients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B. Arm B (High TS, FOLFOX/bev) Oxaliplatin Patients with high TS who are randomized to Arm B receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev). The combination regimen is administered by giving bevacizumab and oxaliplatin as in Arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met.
- Primary Outcome Measures
Name Time Method Objective Response Rate Assessed every 3 months if the patient is within 2 years of registration and every 6 months up to 4 years post-registration. Objective response rate is defined as proportion of patients who achieve complete response (CR) or partial response (PR). Response was assessed using Solid Tumor Response Criteria (RECIST). CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Assessed every 3 months if the patient is within 2 years of registration and every 6 months once the patient is 2-4 years post-registration. Overall survival is defined as time from randomization (to Arm A or Arm B) or registration (to Arm C) to death. Patients alive at last follow-up were censored.
Progression-Free Survival (PFS) Assessed every 3 months if the patient is within 2 years of registration and every 6 months once the patient is 2-4 years post-registration. Progression-free survival is defined as time from randomization (to Arm A or Arm B) or registration (to Arm C) to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
Trial Locations
- Locations (110)
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
St. Mary - Corwin Regional Medical Center
🇺🇸Pueblo, Colorado, United States
Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Licking Memorial Cancer Care Program at Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
Hematology and Oncology Associates
🇺🇸Chicago, Illinois, United States
Saint Joseph Hospital
🇺🇸Chicago, Illinois, United States
Grant Medical Center Cancer Care
🇺🇸Columbus, Ohio, United States
Veterans Affairs Medical Center - Indianapolis
🇺🇸Indianapolis, Indiana, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
Exempla Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Hope Cancer Care Center at Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Parker Adventist Hospital
🇺🇸Parker, Colorado, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
🇺🇸Grand Junction, Colorado, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Minnesota Oncology - Maplewood
🇺🇸Maplewood, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸Saint Joseph, Michigan, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Lakeside Cancer Specialists, PLLC
🇺🇸Saint Joseph, Michigan, United States
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
St. Anthony Central Hospital
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Minnesota Oncology - Woodbury
🇺🇸Woodbury, Minnesota, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
CCOP - MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Doctors Hospital at Ohio Health
🇺🇸Columbus, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
Cancer Resource Center - Lincoln
🇺🇸Lincoln, Nebraska, United States
St. Rita's Medical Center
🇺🇸Lima, Ohio, United States
Roger Maris Cancer Center at MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Riverside Methodist Hospital Cancer Care
🇺🇸Columbus, Ohio, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Willmar Cancer Center at Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
MetroHealth Cancer Care Center at MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Mount Carmel Health - West Hospital
🇺🇸Columbus, Ohio, United States
Immanuel Medical Center
🇺🇸Omaha, Nebraska, United States
Strecker Cancer Center at Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
Knox Community Hospital
🇺🇸Mount Vernon, Ohio, United States
Natalie Warren Bryant Cancer Center at St. Francis Hospital
🇺🇸Tulsa, Oklahoma, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Erlanger Cancer Center at Erlanger Hospital - Baroness
🇺🇸Chattanooga, Tennessee, United States
Community Hospital of Springfield and Clark County
🇺🇸Springfield, Ohio, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
Lakeside Hospital
🇺🇸Omaha, Nebraska, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
Southern Ohio Medical Center Cancer Center
🇺🇸Portsmouth, Ohio, United States
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Genesis - Good Samaritan Hospital
🇺🇸Zanesville, Ohio, United States
Cancer Center of Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
CCOP - Main Line Health
🇺🇸Wynnewood, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
California Cancer Care, Incorporated - Greenbrae
🇺🇸Greenbrae, California, United States
Littleton Adventist Hospital
🇺🇸Littleton, Colorado, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Veterans Affairs Medical Center - Atlanta (Decatur)
🇺🇸Decatur, Georgia, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸Decatur, Illinois, United States
Provena St. Mary's Regional Cancer Center - Kankakee
🇺🇸Kankakee, Illinois, United States
North Shore Oncology and Hematology Associates, Limited - Libertyville
🇺🇸Libertyville, Illinois, United States
Cancer Care and Hematology Specialists of Chicagoland - Niles
🇺🇸Niles, Illinois, United States
Swedish-American Regional Cancer Center
🇺🇸Rockford, Illinois, United States
Hematology Oncology Associates - Skokie
🇺🇸Skokie, Illinois, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Howard Community Hospital
🇺🇸Kokomo, Indiana, United States
William N. Wishard Memorial Hospital
🇺🇸Indianapolis, Indiana, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸La Porte, Indiana, United States
Saint Joseph Regional Medical Center
🇺🇸Mishawaka, Indiana, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
McCreery Cancer Center at Ottumwa Regional
🇺🇸Ottumwa, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
MeritCare Bemidji
🇺🇸Bemidji, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
CCOP - Columbus
🇺🇸Columbus, Ohio, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States