Clinical trial NCT00006786: Combination Chemotherapy Plus Bevacizumab in Treating Patients With Advanced Colorectal Cancer
Official title: Phase II Trial of Fluorouracil (5-FU), Leucovorin (LV), Irinotecan (CPT-11) and Bevacizumab (Anti-VEGF) in Previously Untreated Patients With Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bevacizumab may stop the growth of colorectal cancer by stopping blood flow to the tumor.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus bevacizumab in treating patients who have advanced colorectal cancer.

Detailed description: OBJECTIVES: I. Determine the progression-free survival at 7 months of patients with previously untreated advanced colorectal cancer treated with fluorouracil, leucovorin calcium, irinotecan, and bevacizumab. II. Determine the response rate and overall survival of this patient population treated with this regimen. III. Determine the toxicity of this treatment regimen in these patients.

OUTLINE: This is a multicenter study. Patients receive irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV once weekly for 4 weeks. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed advanced or metastatic adenocarcinoma of the colon and rectum Surgically unresectable disease Measurable disease Disease outside the prior radiotherapy port and/or progressive disease within the previously irradiated volume

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 No hemorrhagic events within the past 6 months Hepatic: Bilirubin normal SGOT normal INR no greater than 1.5 Renal: Creatinine no greater than 1.5 times upper limit of normal Cardiovascular: No thromboembolic events within the past 6 months Pulmonary: No evidence of pneumonia Other: No known hypersensitivity to recombinant humanized murine monoclonal antibodies No evidence of significant active infection (e.g., peritonitis or wound abscess) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent sargramostim (GM-CSF) Chemotherapy: At least 12 months since prior fluorouracil-based adjuvant chemotherapy No prior adjuvant irinotecan Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 2 weeks since prior radiotherapy and recovered Surgery: See Disease Characteristics Other: No prior therapy for advanced disease No concurrent therapeutic anticoagulation except for low-dose coumadin for maintenance of indwelling catheters

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Inc.
state: Colorado
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: MBCCOP-Howard University Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Veterans Affairs Medical Center - Gainsville
state: Florida
city: Miami
country: United States
facility: Veterans Affairs Medical Center - Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at The University of Iowa
state: Iowa
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: New England Medical Center Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: Veterans Affairs Medical Center - Omaha
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Albany
country: United States
facility: Veterans Affairs Medical Center - Albany
state: New York
city: Bronx
country: United States
facility: Albert Einstein Comprehensive Cancer Center
state: New York
city: Bronx
country: United States
facility: MBCCOP-Our Lady of Mercy Cancer Center
state: New York
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: New York
country: United States
facility: Veterans Affairs Medical Center - New York
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Veterans Affairs Medical Center - Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital Oncology Program
state: Ohio
city: Tulsa
country: United States
facility: CCOP - Sooner State
state: Oklahoma
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Health Systems
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans Affairs Medical Center - Pittsburgh
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: MBCCOP - San Juan
city: San Juan
country: Puerto Rico
facility: Veterans Affairs Medical Center - San Juan
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospitals
Study officials:
affiliation: Presbyterian medical center
name: Bruce J. Giantonio, MD
role: STUDY_CHAIR
References:
citation: Giantonio BJ, Chen HX, Catalano PJ, et al.: Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200. [Abstract] J Clin Oncol 22 (Suppl 14): A-3017, 199s, 2004.
citation: Gray R, Giantonio BJ, O'Dwyer PJ, et al.: The safety of adding angiogenesis inhibition into treatment for colorectal, breast, and lung cancer: the Eastern Cooperative Oncology Group's (ECOG) experience with bevacizumab (anti-VEGF). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-825, 2003.
citation: Giantonio BJ, Levy DE, O'dwyer PJ, Meropol NJ, Catalano PJ, Benson AB 3rd; Eastern Cooperative Oncology Group. A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the Eastern Cooperative Oncology Group study E2200. Ann Oncol. 2006 Sep;17(9):1399-403. doi: 10.1093/annonc/mdl161. Epub 2006 Jul 27.
citation: Giantonio BJ, Levy D, O'Dwyer PJ, et al.: Bevacizumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC): results from the Eastern Cooperative Oncology Group (ECOG) Study E2200. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1024, 2003.
citation: Giantonio BJ, Levy D, Catalano PJ, et al.: Incorporating angiogenesis inhibition with bevacizumab (anti-VEGF) into frontline chemotherapy with irinotecan (CPT-11), fluorouracil and leucovorin (FU/LV) for advanced colorectal cancer (advCRC): a toxicity analysis of ECOG study E2200. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-503, 2002.