Combination Chemotherapy Plus Bevacizumab in Treating Patients With Advanced Colorectal Cancer

Phase II Trial of Fluorouracil (5-FU), Leucovorin (LV), Irinotecan (CPT-11) and Bevacizumab (Anti-VEGF) in Previously Untreated Patients With Advanced Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Biological: bevacizumab

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927-5800
    • MBCCOP - San Juan
  • San Juan, Puerto Rico, 00927-5800
    • Veterans Affairs Medical Center - San Juan
• South Africa
  • Pretoria, South Africa, 0001
    • Pretoria Academic Hospitals
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Scottsdale Oncology Program
  • California
    • Duarte, California, United States, 91010-3000
      • Cancer Center and Beckman Research Institute, City of Hope
    • Palo Alto, California, United States, 94304
      • Veterans Affairs Medical Center - Palo Alto
    • Stanford, California, United States, 94305-5408
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80209-5031
      • CCOP - Colorado Cancer Research Program, Inc.
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
    • Washington, District of Columbia, United States, 20060
      • MBCCOP-Howard University Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32608-1197
      • Veterans Affairs Medical Center - Gainsville
    • Miami, Florida, United States, 33125
      • Veterans Affairs Medical Center - Miami
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
    • Decatur, Georgia, United States, 30033
      • Veterans Affairs Medical Center - Atlanta (Decatur)
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Chicago, Illinois, United States, 60611
      • Veterans Affairs Medical Center - Lakeside Chicago
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Evanston, Illinois, United States, 60201
      • CCOP - Evanston
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Veterans Affairs Medical Center - Indianapolis (Roudebush)
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at the University of Iowa
  • Kansas
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68105
      • Veterans Affairs Medical Center - Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
  • New Jersey
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Affairs Medical Center - East Orange
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute of New Jersey
  • New York
    • Albany, New York, United States, 12208
      • Veterans Affairs Medical Center - Albany
    • Bronx, New York, United States, 10461
      • Albert Einstein Comprehensive Cancer Center
    • Bronx, New York, United States, 10466
      • MBCCOP-Our Lady of Mercy Cancer Center
    • Brooklyn, New York, United States, 11209
      • Veterans Affairs Medical Center - Brooklyn
    • New York, New York, United States, 10016
      • NYU School of Medicine's Kaplan Comprehensive Cancer Center
    • New York, New York, United States, 10010
      • Veterans Affairs Medical Center - New York
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Veterans Affairs Medical Center - Cleveland
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital Oncology Program
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • CCOP - Sooner State
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • CCOP - Geisinger Clinic and Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19102-1192
      • Hahnemann University Hospital
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • University of Pennsylvania Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104-9104
      • University of Pennsylvania Health Systems
    • Pittsburgh, Pennsylvania, United States, 15213-3489
      • University of Pittsburgh Cancer Institute
    • Pittsburgh, Pennsylvania, United States, 15240
      • Veterans Affairs Medical Center - Pittsburgh
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105-1080
      • CCOP - Sioux Community Cancer Consortium
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37212
      • Veterans Affairs Medical Center - Nashville
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Comprehensive Cancer Center
    • Madison, Wisconsin, United States, 53705
      • Veterans Affairs Medical Center - Madison
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Medical Research and Education Foundation
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee (Zablocki)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Bruce J. Giantonio, MD, Presbyterian Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2000
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: December 6, 2000
• First Submitted That Met QC Criteria: February 11, 2004
• First Posted (Estimate): February 12, 2004

Study Record Updates

• Last Update Posted (Estimate): June 24, 2013
• Last Update Submitted That Met QC Criteria: June 20, 2013
• Last Verified: September 1, 2006

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000068328; ECOG-E2200