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| Sponsor: | Genentech |
|---|---|
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00012233 |
Purpose
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether monoclonal antibody therapy is more effective with or without irinotecan in treating metastatic colorectal cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without irinotecan plus monoclonal antibody therapy in treating patients who have metastatic colorectal cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer |
Biological: bevacizumab Drug: FOLFIRI regimen Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium |
Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | A Phase III, Multicenter, Randomized, Active-Controlled Clinical Trial to Evaluate the Efficacy and Safety of rhuMAb VEGF (Bevacizumab) in Combination With Standard Chemotherapy in Subjects With Metastatic Colorectal Cancer |
| Study Start Date: | July 2000 |
OBJECTIVES: I. Evaluate the efficacy, in terms of duration of survival, time to disease progression, objective response rate, and duration of objective response of bevacizumab (rhuMAb VEGF) with fluorouracil, leucovorin calcium, and irinotecan as opposed to placebo with fluorouracil, leucovorin calcium, and irinotecan in patients with metastatic colorectal cancer. II. Evaluate the safety of these regimens in these patients. III. Determine the plasma pharmacokinetics of irinotecan with fluorouracil, leucovorin calcium, and bevacizumab (rhuMAb VEGF) versus irinotecan with fluorouracil and leucovorin calcium in these patients. IV. Determine the pharmacokinetics of bevacizumab (rhuMAb VEGF) in these patients. V. Evaluate and compare the quality of life in patients treated with these regimens.
OUTLINE: This is a randomized, active-controlled, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), site of primary disease (colon vs rectum), and number of metastatic sites (1 vs more than 1). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 1-2 minutes and fluorouracil IV over 1-2 minutes weekly for 4 weeks. Patients also receive placebo IV over 30-90 minutes every other week. Courses repeat every 6 weeks. Arm II: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in arm I. Patients also receive bevacizumab (rhuMAb VEGF) IV over 30-90 minutes every other week. Courses repeat every 6 weeks. Treatment continues for a maximum of 16 courses in the absence of disease progression or unacceptable toxicity. All patients with progressive disease may continue to receive treatment on this study with another chemotherapy agent with or without bevacizumab (rhuMAb VEGF). Patients in arm I with progressive disease may continue to receive another chemotherapy agent and are not allowed to receive bevacizumab (rhuMAb VEGF). Patients in arm II with progressive disease may continue to receive bevacizumab (rhuMAb VEGF) alone or in combination with another chemotherapy agent. Patients are followed every 4 months for survival.
PROJECTED ACCRUAL: Approximately 900 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Histologically confirmed metastatic colorectal cancer At least 2 bidimensionally measurable lesions No CNS disease (e.g., primary brain tumor, seizures not controlled with standard therapy, or any brain metastases) No clinically detectable ascites
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: More than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 75,000/mm3 Hemoglobin at least 9 g/dL (may be transfused) No bleeding diathesis or coagulopathy Hepatic: AST or ALT no greater than 2.5 times upper limit of normal (ULN) (less than 5 times ULN if liver metastasis present) Bilirubin no greater than 1.6 mg/dL International normalized ratio less than 1.5 Renal: Creatinine no greater than 2.0 mg/dL No proteinuria or clinically significant impairment of renal function Cardiovascular: No clinically significant cardiovascular disease including uncontrolled hypertension, myocardial infarction, or unstable angina within past year No New York Heart Association class II-IV congestive heart failure within past year No serious cardiac arrhythmia requiring medication or grade II or greater peripheral vascular disease within past year Other: Must be able to tolerate CT scan contrast dye No other invasive malignancy within past 5 years except basal cell skin cancer No CNS disease including uncontrolled seizures or stroke No active infection requiring parenteral antibiotics No serious nonhealing wound, ulcer, or bone fracture No other disease or medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for colorectal cancer Chemotherapy: At least 12 months since prior fluoropyrimidines with leucovorin and/or levamisole No other prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 14 days since prior radiotherapy No prior radiotherapy to any indicator lesion Surgery: At least 28 days since prior surgical procedure At least 7 days since prior fine needle aspiration No concurrent major surgical procedure Other: At least 10 days since prior full-dose oral or parenteral anticoagulants except to maintain patency of pre-existing, permanent indwelling IV catheters At least 10 days since prior full-dose oral or parenteral thrombolytic agent At least 28 days since participation in other experimental drug study No chronic, daily aspirin or nonsteroidal anti-inflammatory medications No concurrent full-dose oral or parenteral anticoagulants (except for indwelling IV catheter maintenance) or thrombolytic agent
Contacts and Locations
Hide Study Locations| United States, Alabama | |
| Carraway Cancer Center | |
| Birmingham, Alabama, United States, 35234 | |
| Medical Center East | |
| Birmingham, Alabama, United States, 35235-3401 | |
| University of Alabama at Birmingham Comprehensive Cancer Center | |
| Birmingham, Alabama, United States, 35294-3300 | |
| US Oncology, Birmingham Hematology and Oncology Associates | |
| Alabaster, Alabama, United States, 35007 | |
| United States, Arkansas | |
| Highlands Oncology Group, P.A. | |
| Fayetteville, Arkansas, United States, 72703 | |
| United States, California | |
| Alan B. Newman MD and Associates | |
| San Francisco, California, United States, 94115 | |
| Alta Bates Comprehensive Cancer Center | |
| Berkeley, California, United States, 94704 | |
| Hoag Memorial Hospital Presbyterian | |
| Newport Beach, California, United States, 92658 | |
| UCSF Cancer Center and Cancer Research Institute | |
| San Francisco, California, United States, 94143-0128 | |
| Kaiser Permanente Medical Center - Vallejo | |
| Vallejo, California, United States, 94589 | |
| Kaiser Permanente-Southern California Permanente Medical Group | |
| San Diego, California, United States, 92120 | |
| Loma Linda University Medical Center | |
| Loma Linda, California, United States, 92354 | |
| Pacific Coast Hematology/Oncology Medical Group | |
| Fountain Valley, California, United States, 92708 | |
| Pacific Hematology/Oncology | |
| San Francisco, California, United States, 94115 | |
| Southwest Cancer Care | |
| Escondido, California, United States, 92025-4404 | |
| Sutter Cancer Center | |
| Sacramento, California, United States, 95816 | |
| Jonsson Comprehensive Cancer Center, UCLA | |
| Los Angeles, California, United States, 90095-1781 | |
| University of California Davis Medical Center | |
| Sacramento, California, United States, 95817 | |
| University of California Los Angeles School of Medicine | |
| Los Angeles, California, United States, 90095 | |
| USC/Norris Comprehensive Cancer Center and Hospital | |
| Los Angeles, California, United States, 90033-0804 | |
| United States, Colorado | |
| Boulder Valley Oncology, LLP | |
| Boulder, Colorado, United States, 80304 | |
| Rocky Mountain Cancer Center | |
| Englewood, Colorado, United States, 80110 | |
| The Oncology Clinic, P.C. | |
| Colorado Springs, Colorado, United States, 80907 | |
| US Oncology - Rocky Mountain Cancer Center | |
| Littleton, Colorado, United States, 80120 | |
| US Oncology, Rocky Mountain Cancer Centers | |
| Lakewood, Colorado, United States, 80228 | |
| United States, Connecticut | |
| Helen and Harry Gray Cancer Center | |
| Hartford, Connecticut, United States, 06106 | |
| Hematology Oncology, P.C. | |
| Stamford, Connecticut, United States, 06902 | |
| Northwestern Connecticut Oncology-Hematology Associates | |
| Torrington, Connecticut, United States, 06790 | |
| St. Francis Hospital and Medical Center | |
| Hartford, Connecticut, United States, 06105 | |
| Yale Comprehensive Cancer Center | |
| New Haven, Connecticut, United States, 06520-8028 | |
| United States, District of Columbia | |
| Washington Cancer Institute | |
| Washington, District of Columbia, United States, 20010 | |
| United States, Florida | |
| Cancer Research Network Inc. | |
| Plantation, Florida, United States, 33324 | |
| Cedars Medical Center | |
| Miami, Florida, United States, 33136 | |
| Center for Hematology-Oncology | |
| Boca Raton, Florida, United States, 33486 | |
| Comprehensive Cancer Care Specialists of Boca Raton | |
| Boca Raton, Florida, United States, 33428 | |
| Florida Cancer Specialists | |
| Fort Myers, Florida, United States, 33901 | |
| Florida Oncology Associates | |
| Orange Park, Florida, United States, 32073 | |
| Mount Sinai Comprehensive Cancer Center | |
| Miami, Florida, United States, 33140 | |
| Ocala Oncology Center | |
| Ocala, Florida, United States, 34474 | |
| Walt Disney Memorial Cancer Institute | |
| Orlando, Florida, United States, 32803 | |
| Oncology Radiation Associates | |
| Miami, Florida, United States, 33133 | |
| US Oncology - Florida Community Cancer Center | |
| Bradenton, Florida, United States, 34209 | |
| Oncology Hematology Consultants, PA | |
| Sarasota, Florida, United States, 34239 | |
| United States, Georgia | |
| American Medical Research Institute, Inc. | |
| Cumming, Georgia, United States, 30040 | |
| Northwest Georgia Oncology Centers, P.C. | |
| Marietta, Georgia, United States, 30060 | |
| Piedmont Hospital, Inc. | |
| Atlanta, Georgia, United States, 30309 | |
| United States, Illinois | |
| Carle Cancer Center | |
| Urbana, Illinois, United States, 61801 | |
| Lutheran General Cancer Care Center | |
| Park Ridge, Illinois, United States, 60068 | |
| Midwest Clinical Research Group, Inc. | |
| Highland Park, Illinois, United States, 60035 | |
| Rush North Shore Medical Center | |
| Skokie, Illinois, United States, 60076 | |
| United States, Indiana | |
| Oncology/Hematology Associates | |
| Indianapolis, Indiana, United States, 46227 | |
| United States, Kansas | |
| Oncology/Hematology Associates | |
| Overland Park, Kansas, United States, 66210 | |
| University of Kansas Medical Center | |
| Kansas City, Kansas, United States, 66160-7357 | |
| United States, Kentucky | |
| Consultants in Blood Disorders and Cancer | |
| Louisville, Kentucky, United States, 40207 | |
| Norton Healthcare Pavilion | |
| Louisville, Kentucky, United States, 40202 | |
| United States, Louisiana | |
| Louisiana Oncology Associates | |
| Lafayette, Louisiana, United States, 70506 | |
| Mary Bird Perkins Cancer Center | |
| Baton Rouge, Louisiana, United States, 70809 | |
| Ochsner Cancer Institute | |
| New Orleans, Louisiana, United States, 70121 | |
| United States, Maine | |
| Maine Center for Cancer Medicine and Blood Disorders | |
| Scarborough, Maine, United States, 04074 | |
| United States, Maryland | |
| Associates in Oncology and Hematology | |
| Rockville, Maryland, United States, 20850 | |
| Greater Baltimore Medical Center and Cancer Center | |
| Baltimore, Maryland, United States, 21204 | |
| United States, Massachusetts | |
| New England Hematology/Oncology Associates, P.C. | |
| Wellesley, Massachusetts, United States, 02181 | |
| St. Elizabeth's Medical Center of Boston | |
| Brighton, Massachusetts, United States, 02135 | |
| United States, Michigan | |
| Henry Ford Hospital | |
| Detroit, Michigan, United States, 48202 | |
| Offices of R.H. Clark and J.A. Axelson | |
| Jackson, Michigan, United States, 49201 | |
| Oncology and Hematology, P.C. | |
| Kalamazoo, Michigan, United States, 49007 | |
| Southfield Oncology Institute, Inc. | |
| Southfield, Michigan, United States, 48076 | |
| United States, Minnesota | |
| Minnesota Oncology-Hematology, P.A. | |
| Minneapolis, Minnesota, United States, 55407 | |
| United States, Missouri | |
| Ellis Fischel Cancer Center - Columbia | |
| Columbia, Missouri, United States, 65203 | |
| Midwest Oncology Consortium | |
| Kansas City, Missouri, United States, 64111 | |
| Missouri Cancer Care, P.C. | |
| St. Charles, Missouri, United States, 63301 | |
| Oncology Hematology Associates of Kansas City | |
| Kansas City, Missouri, United States, 64131 | |
| St. John's Mercy Medical Center | |
| Saint Louis, Missouri, United States, 63141 | |
| Washington University Siteman Cancer Center | |
| Saint Louis, Missouri, United States, 63110 | |
| United States, Nebraska | |
| University of Nebraska Medical Center | |
| Omaha, Nebraska, United States, 68198-3330 | |
| United States, Nevada | |
| University Medical Center - Las Vegas | |
| Las Vegas, Nevada, United States, 89102-2386 | |
| Veterans Affairs Medical Center - Reno | |
| Reno, Nevada, United States, 89520 | |
| United States, New Jersey | |
| Hackensack University Medical Center | |
| Hackensack, New Jersey, United States, 07601 | |
| Overlook Hospital | |
| Summit, New Jersey, United States, 07902-0220 | |
| Saint Clare's Hospital | |
| Denville, New Jersey, United States, 07834 | |
| United States, New Mexico | |
| Veterans Affairs Medical Center - Albuquerque | |
| Albuquerque, New Mexico, United States, 87108-5138 | |
| United States, New York | |
| Interlakes Oncology/Hematology PC | |
| Rochester, New York, United States, 14623 | |
| Cancer Research of Long Island, Inc. | |
| Great Neck, New York, United States, 11022 | |
| HemOnCare, P.C. | |
| Brooklyn, New York, United States, 11235 | |
| Advanced Oncology Associates | |
| Armonk, New York, United States, 10504 | |
| Milstein Hospital Building | |
| New York, New York, United States, 10032 | |
| New York Presbyterian Hospital - Cornell Campus | |
| New York, New York, United States, 10021 | |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | |
| New York, New York, United States, 10016 | |
| St. Luke's-Roosevelt Hospital | |
| New York, New York, United States, 10019 | |
| US Oncology, Rocky Mountain Cancer Center | |
| Albany, New York, United States, 12203 | |
| Veterans Affairs Medical Center - Albany | |
| Albany, New York, United States, 12208 | |
| United States, North Carolina | |
| Asheville Hematology and Oncology Associates, P.A. | |
| Asheville, North Carolina, United States, 28801 | |
| Carolinas Medical Center | |
| Charlotte, North Carolina, United States, 28232-2861 | |
| CCOP - Southeast Cancer Control Consortium | |
| Winston-Salem, North Carolina, United States, 27104-4241 | |
| Duke Comprehensive Cancer Center | |
| Durham, North Carolina, United States, 27710 | |
| Lineberger Comprehensive Cancer Center, UNC | |
| Chapel Hill, North Carolina, United States, 27599-7295 | |
| N.W. Carolina Oncology & Hematology, P.A. | |
| Hickory, North Carolina, United States, 28603 | |
| nTouch Research Corporation | |
| Raleigh, North Carolina, United States, 27610 | |
| Raleigh Hematology Oncology Associates, P.C. | |
| Raleigh, North Carolina, United States, 27607 | |
| Raleigh Internal Medicine | |
| Raleigh, North Carolina, United States, 27609 | |
| Regional Hematology Oncology Associates | |
| Durham, North Carolina, United States, 27704 | |
| United States, Ohio | |
| Barrett Cancer Center, The University Hospital | |
| Cincinnati, Ohio, United States, 45219 | |
| Haematology-Oncology Associates, Inc. | |
| Toledo, Ohio, United States, 43623-4474 | |
| Mid-Ohio Oncology/Hematology, Inc. | |
| Columbus, Ohio, United States, 43222 | |
| United States, Oklahoma | |
| nTouch Research | |
| Oklahoma City, Oklahoma, United States, 73109 | |
| Oklahoma Oncology Inc. | |
| Tulsa, Oklahoma, United States, 74104 | |
| University of Oklahoma Health Sciences Center | |
| Oklahoma City, Oklahoma, United States, 73190 | |
| United States, Oregon | |
| Kaiser Permanente - Portland | |
| Portland, Oregon, United States, 97227 | |
| United States, Pennsylvania | |
| Hematology/Oncology Associates of NE Pennsylvania, P.C. | |
| Scranton, Pennsylvania, United States, 18510 | |
| Milton S. Hershey Medical Center | |
| Hershey, Pennsylvania, United States, 17033-0850 | |
| University of Pennsylvania Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19104-4283 | |
| United States, South Carolina | |
| Palmetto Richland Memorial Hospital | |
| Columbia, South Carolina, United States, 29203 | |
| Spartanburg Regional Healthcare System | |
| Spartanburg, South Carolina, United States, 29303 | |
| Veterans Affairs Medical Center - Columbia | |
| Columbia, South Carolina, United States, 20209 | |
| United States, Tennessee | |
| Baptist Regional Cancer Center - Knoxville | |
| Knoxville, Tennessee, United States, 37901 | |
| University of Tennessee, Memphis Cancer Center | |
| Memphis, Tennessee, United States, 38103 | |
| Sarah Cannon-Minnie Pearl Cancer Center | |
| Nashville, Tennessee, United States, 37203 | |
| University of Tennessee, Memphis | |
| Memphis, Tennessee, United States, 38163 | |
| Dial Research Associates | |
| Brentwood, Tennessee, United States, 37027 | |
| Vanderbilt-Ingram Cancer Center | |
| Nashville, Tennessee, United States, 37232-6838 | |
| United States, Texas | |
| Scott and White Clinic | |
| Temple, Texas, United States, 76508 | |
| Texas Oncology, P.A. | |
| Dallas, Texas, United States, 75231 | |
| Texas Oncology, P.A. | |
| Austin, Texas, United States, 78745 | |
| US Oncology (Texas Oncology) PA | |
| Houston, Texas, United States, 77030 | |
| US Oncology, Texas Cancer Center | |
| Denton, Texas, United States, 76205 | |
| United States, Utah | |
| Intermountain Hematology/Oncology Associates, Inc. | |
| Salt Lake City, Utah, United States, 84124 | |
| United States, Virginia | |
| Hematology & Oncology Associates of Virginia | |
| Richmond, Virginia, United States, 23226 | |
| Northern Virginia Oncology Group, P.C. | |
| Fairfax, Virginia, United States, 22031 | |
| United States, Washington | |
| Madigan Army Medical Center | |
| Tacoma, Washington, United States, 98431-5000 | |
| Northwest Cancer Specialists | |
| Vancouver, Washington, United States, 98664 | |
| Swedish Cancer Institute | |
| Seattle, Washington, United States, 98104 | |
| Virginia Mason Medical Center | |
| Seattle, Washington, United States, 98111 | |
| Western Washington Oncology, Inc. | |
| Olympia, Washington, United States, 98502 | |
| United States, Wisconsin | |
| Marshfield Clinic - Lakeland Center | |
| Minocqua, Wisconsin, United States, 54548 | |
| Medical College of Wisconsin | |
| Milwaukee, Wisconsin, United States, 53226 | |
| Rhinelander Medical Center | |
| Rhinelander, Wisconsin, United States, 54501 | |
| Study Chair: | Beth Drena | Genentech |
More Information
| Study ID Numbers: | CDR0000068496, GENENTECH-AVF2107g, UCLA-0008022 |
| Study First Received: | March 3, 2001 |
| Last Updated: | November 16, 2009 |
| ClinicalTrials.gov Identifier: | NCT00012233 History of Changes |
| Health Authority: | United States: Federal Government |
|
stage IV colon cancer stage IV rectal cancer |
|
Antimetabolites Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Immunologic Factors Gastrointestinal Diseases Antineoplastic Agents Irinotecan Colonic Diseases Physiological Effects of Drugs Leucovorin Bevacizumab Rectal Diseases Neoplasms by Site Vitamins Therapeutic Uses |
Growth Inhibitors Angiogenesis Modulating Agents Micronutrients Vitamin B Complex Digestive System Neoplasms Growth Substances Enzyme Inhibitors Intestinal Diseases Angiogenesis Inhibitors Immunosuppressive Agents Intestinal Neoplasms Camptothecin Pharmacologic Actions Neoplasms Digestive System Diseases |