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Monoclonal Antibody Therapy Plus Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer
This study is ongoing, but not recruiting participants.
First Received: March 3, 2001   Last Updated: November 16, 2009   History of Changes
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: July 2000
Detailed Description:

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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00012233

  Hide Study Locations
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
Sponsors and Collaborators
Genentech
Investigators
Study Chair: Beth Drena Genentech
  More Information

Additional Information:
Publications:
Hurwitz HI, Zurlo A, Irl C, et al.: Analysis of outcomes of patients with metastatic colorectal cancer (mCRC) treated with IFL with or without bevacizumab (BV) in a phase III clinical trial based on baseline risk. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-249, 2006.
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42.
Cassidy J, Saltz LB, Giantonio BJ, Kabbinavar FF, Hurwitz HI, Rohr UP. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol. 2009 Nov 11; [Epub ahead of print]
Kabbinavar FF, Hurwitz HI, Yi J, Sarkar S, Rosen O. Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol. 2009 Jan 10;27(2):199-205. Epub 2008 Dec 8.
Grothey A, Hedrick EE, Mass RD, Sarkar S, Suzuki S, Ramanathan RK, Hurwitz HI, Goldberg RM, Sargent DJ. Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J Clin Oncol. 2008 Jan 10;26(2):183-9.
Grothey A, Hedrick EE, Mass RD, et al.: Response rate using conventional criteria is a poor surrogate for clinical benefit on progression-free (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC): a comparative analysis of N9741 and AVF2107. [Abstract] J Clin Oncol 24 (Suppl 18): A-3516, 2006.

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

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on November 25, 2009