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Combination Chemotherapy With or Without Bevacizumab 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: NCT00012272
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy is more effective with or without bevacizumab in treating colorectal cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy with or without bevacizumab in treating patients who have metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Active Control
Official Title: A Phase II, Multicenter, Double-Blind, Randomized, Active-Controlled Clinical Trial to Evaluate the Efficacy and Safety of rhuMAb VEGF, A Recombinant Humanized Monoclonal Antibody to Vascular Endothelial Growth Factor in Combination With 5-Fluorouracil and Leucovorin Chemotherapy in Subjects With Metastatic Colorectal Cancer Who Are Not Optimal Candidates for First-Line CPT-11

Resource links provided by NLM:


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

Study Start Date: June 2000
Detailed Description:

OBJECTIVES: I. Compare the efficacy of fluorouracil and leucovorin calcium with and without bevacizumab, in terms of duration of survival, objective response rate, duration of response, time to disease progression, and change in quality of life, in patients with previously untreated metastatic colorectal cancer. II. Compare the safety of these regimens in these patients. III. Assess the safety and preliminary efficacy of bevacizumab combined with irinotecan in these patients. IV. Assess the pharmacokinetics of irinotecan in these patients.

OUTLINE: This is a randomized, double-blind, active-controlled, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1 or higher), site of primary disease (colon vs rectum), and number of metastatic sites (1 vs more than 1). Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour weekly for the first 6 weeks of each 8 week course. Study drug, bevacizumab is administered IV over 30-90 minutes every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive leucovorin calcium and fluorouracil as in arm I and placebo IV over 30-90 minutes every 2 weeks. Treatment continues for up to a total of 48 doses of bevacizumab or a maximum of 96 weeks of therapy. Patients on arm I who have disease progression may continue bevacizumab with or without irinotecan IV over 90 minutes weekly for 4 weeks, with courses repeating every 6 weeks. Patients on arm II who have disease progression may not receive second-line bevacizumab. Patients on either arm who have disease progression may receive irinotecan alone as second-line treatment. Quality of life is assessed every 3-5 weeks. Patients are followed every 4 months for survival.

PROJECTED ACCRUAL: A total of 200 patients (100 per arm) 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, previously untreated, metastatic colorectal carcinoma Bidimensionally measurable disease (minimum of two lesions) Not an optimal candidate for first-line irinotecan Must meet at least one of the following criteria: Age 65 years or over ECOG performance status 1-2 Albumin no greater than 3.5 g/dL Prior radiotherapy to the abdomen or pelvis 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: See Disease Characteristics 18 and over Performance status: See Disease Characteristics ECOG 0-2 Life expectancy: More than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count greater than 75,000/mm3 Hemoglobin at least 9 g/dL (transfusion allowed) No bleeding diathesis or coagulopathy Hepatic: See Disease Characteristics Bilirubin no greater than 2.0 mg/dL AST/ALT no greater than 2.5 times upper limit of normal (ULN)(less than 5 times ULN if liver metastases present) INR less than 1.5 Renal: No history of proteinuria No clinically significant impairment of renal function Creatinine no greater than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension, myocardial infarction, or unstable angina within the past year No New York Heart Association class II or higher congestive heart failure within the past year No serious cardiac arrhythmia requiring medication or grade II or higher peripheral vascular disease within the past year Other: Able to tolerate CT scan contrast dye Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except basal cell carcinoma of the skin No serious nonhealing wound, ulcer, significant traumatic injury, or bone fracture No concurrent active infection requiring parenteral antibiotics No metabolic dysfunction or other medical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for colorectal cancer No concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 12 months since prior adjuvant fluoropyrimidines in combination with leucovorin calcium and/or levamisole No other prior chemotherapy No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to target lesions At least 12 months since prior administration of fluoropyrimidines as a radiosensitizer during pelvic radiotherapy for rectal cancer completed less than 12 months prior to study At least 14 days since prior radiotherapy No concurrent radiotherapy Surgery: At least 28 days since prior major surgery At least 7 days since prior fine needle aspiration No concurrent open biopsy or anticipated need for major surgery Other: At least 10 days since prior chronic use of oral or parenteral anticoagulants (except as needed to maintain patency of indwelling IV catheters) or thrombolytic agents At least 28 days since participation in other experimental drug study No concurrent oral or parenteral anticoagulants (except as needed to maintain patency of indwelling IV catheters) or thrombolytic agents No concurrent chronic daily aspirin or nonsteroidal anti-inflammatory medications known to inhibit platelet function

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00012272

  Hide Study Locations
Locations
United States, Alabama
Comprehensive Cancer Institute of Huntsville
Huntsville, Alabama, United States, 35801
United States, Arizona
Mesa Cancer Resource Network
Mesa, Arizona, United States, 85201
United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Kaiser Permanente-Southern California Permanente Medical Group
San Diego, California, United States, 92120
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
United States, Colorado
US Oncology - Rocky Mountain Cancer Center
Colorado Springs, Colorado, United States, 80538
US Oncology - Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
US Oncology - Rocky Mountain Cancer Center
Colorado Springs, Colorado, United States, 80907
United States, Connecticut
Hematology Oncology, P.C.
Stamford, Connecticut, United States, 06902
United States, Florida
Cancer Research Network Inc.
Plantation, Florida, United States, 33324
Center for Hematology-Oncology
Boca Raton, Florida, United States, 33486
US Oncology - Florida Community Cancer Center
Clearwater, Florida, United States, 33761
Florida Community Cancer Center
Hudson, Florida, United States, 34667
Oncology Radiation Associates
Miami, Florida, United States, 33133
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
US Oncology - Florida Community Cancer Centers
Palm Harbor, Florida, United States, 34684
US Oncology - Florida Community Cancer Centers
New Port Richey, Florida, United States, 34652
US Oncology - Lauderhill Lakes
Plantation, Florida, United States, 33324
US Oncology - North Florida Hematology & Oncology Association
Jacksonville, Florida, United States, 32204
US Oncology - Ocala Oncology, PA
Ocala, Florida, United States, 34470
Walt Disney Memorial Cancer Institute
Orlando, Florida, United States, 32803
United States, Georgia
Piedmont Hospital, Inc.
Atlanta, Georgia, United States, 30309
United States, Illinois
Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Kentucky
Norton Healthcare Pavilion
Louisville, Kentucky, United States, 40202
United States, Louisiana
Louisiana Oncology Associates
Lafayette, Louisiana, United States, 70506
United States, Maryland
Associates in Oncology and Hematology
Rockville, Maryland, United States, 20850
Carroll County Cancer Center
Westminster, Maryland, United States, 21157
Greater Baltimore Medical Center and Cancer Center
Baltimore, Maryland, United States, 21204
United States, Massachusetts
US Oncology - Berkshire Hematology Oncology, PC
Pittsfield, Massachusetts, United States, 01201
United States, Minnesota
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
Missouri Cancer Care, P.C.
St. Charles, Missouri, United States, 63301
St. John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, Montana
Billings Oncology Associates
Billings, Montana, United States, 59101
United States, New Jersey
Trinitas Hospital - Jersey Street Campus
Elizabeth, New Jersey, United States, 07201
United States, New York
North Shore Hematology/Oncology Associates, P.C.
East Setauket, New York, United States, 11733
Cancer Research of Long Island, Inc.
Great Neck, New York, United States, 11022
New York Presbyterian Hospital - Cornell Campus
New York, New York, United States, 10021
Advanced Oncology Associates
Armonk, New York, United States, 10504
US Oncology - Albany Regional Cancer Center
Albany, New York, United States, 12208
Veterans Affairs Medical Center - Albany
Albany, New York, United States, 12208
United States, North Carolina
N.W. Carolina Oncology & Hematology, P.A.
Hickory, North Carolina, United States, 28603
Southeastern Medical Oncology Center
Goldsboro, North Carolina, United States, 27534
US Oncology - Triad Hematology-Oncology
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Mid-Ohio Oncology/Hematology, Inc.
Columbus, Ohio, United States, 43222
US Oncology - Dayton Oncology-Hematology Consultants
Dayton, Ohio, United States, 45439
United States, Oklahoma
US Oncology - Cancer Care Associates
Tulsa, Oklahoma, United States, 74136-1902
United States, Pennsylvania
Hematology/Oncology Associates of NE Pennsylvania, P.C.
Scranton, Pennsylvania, United States, 18510
United States, South Carolina
South Carolina Oncology Associates
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
Sarah Cannon-Minnie Pearl Cancer Center
Nashville, Tennessee, United States, 37203
United States, Texas
US Oncology
Dallas, Texas, United States, 75246
US Oncology - North Texas Regional Cancer Center
Plano, Texas, United States, 75075-7787
US Oncology - South Texas Cancer Center - McAllen
McAllen, Texas, United States, 78503-1298
US Oncology - Texas Cancer Center
Fort Worth, Texas, United States, 76104-2343
US Oncology - Texas Oncology, PA
Fort Worth, Texas, United States, 76104-3902
US Oncology - Texas Oncology, PA
Dallas, Texas, United States, 75246
US Oncology - Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Utah
Intermountain Hematology/Oncology Associates, Inc.
Salt Lake City, Utah, United States, 84124
United States, Virginia
US Oncology - Virginia Oncology Associates
Newport News, Virginia, United States, 23606
United States, Wisconsin
Rhinelander Medical Center
Rhinelander, Wisconsin, United States, 54501
Sponsors and Collaborators
Genentech
Investigators
Study Chair: Brent Perrou, MD Genentech
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000068499, GENENTECH-AVF2192g
Study First Received: March 3, 2001
Last Updated: November 16, 2009
ClinicalTrials.gov Identifier: NCT00012272     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 27, 2009