Bevacizumab Plus Fluorouracil and Leucovorin in Treating Patients With Locally Advanced or Metastatic Stage IV Colorectal Cancer That Has Progressed After Standard Chemotherapy

A Multicenter Study of the Anti-VEGF Monoclonal Antibody Bevacizumab (Avastin®) Plus 5-Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancers That Have Progressed After Standard Chemotherapy

RATIONALE: Bevacizumab may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as fluorouracil and leucovorin use different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with fluorouracil and leucovorin may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining bevacizumab with fluorouracil and leucovorin in treating patients who have locally advanced or metastatic stage IV colorectal cancer that has progressed after standard chemotherapy.

Study Overview

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

Detailed Description

OBJECTIVES:

• Determine the response rate of patients treated with bevacizumab, fluorouracil, and leucovorin calcium for stage IV colorectal cancer that has progressed after standard chemotherapy.
• Determine the time to progression and overall survival of patients treated with this regimen.
• Determine the safety of administering "bolus" and continuous infusion fluorouracil and leucovorin calcium in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study. Patients receive 1 of 2 treatment regimens.

• Regimen I: Patients receive bevacizumab IV on days 1, 15, 29, and 42 (every 2 weeks) and leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV bolus on days 1, 8, 15, 22, 29, and 36.
• Regimen II: Patients receive bevacizumab as in regimen I and CF IV over 2 hours and 5-FU IV bolus followed by a continuous infusion over 22 hours on days 1, 2, 15, 16, 29, 30, 43, and 44.

For both regimens, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for tumor response and survival.

PROJECTED ACCRUAL: Various NCI-designated Clinical Cancer Centers and other medical institutions across the United States will participate in this study. A total of 35-125 patients will be accrued for this study within 3 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99519-6604
      • Providence Alaska Medical Center
  • California
    • Los Angeles, California, United States, 90033-0804
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Los Angeles, California, United States, 90024
      • Jonsson Comprehensive Cancer Center, UCLA
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Maine
    • Bangor, Maine, United States, 04401
      • Cancer Care of Maine
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Health System
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Mary's/Duluth Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Southern Nevada Cancer Research Foundation
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Meritcare Roger Maris Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of The University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sioux Valley Clinics - Oncology
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center

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 or cytologically confirmed colorectal adenocarcinoma

  • Stage IV (metastatic) disease
  • Not curable by surgery or radiotherapy

• Must have received prior standard chemotherapy regimens, including oxaliplatin and irinotecan, and meet both of the following criteria:

  • Disease progression during or after irinotecan-based chemotherapy for metastatic disease OR relapsed disease within 6 months after adjuvant irinotecan-based therapy
  • Disease progression during or after oxaliplatin-based chemotherapy for metastatic disease OR relapsed disease within 6 months after adjuvant oxaliplatin-based therapy
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL (transfusion allowed)
• No evidence of bleeding diathesis or coagulopathy

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST less than 5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 5 times ULN
• PT and INR no greater than 1.5 times ULN
• PTT no greater than ULN

Renal

• Creatinine no greater than 1.5 times ULN
• Proteinuria less than grade 1 OR
• Proteinuria less than 500 mg/24 hours

Cardiovascular

• No prior stroke
• No uncontrolled high blood pressure
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No myocardial infarction within the past 6 months
• No New York Heart Association class III or IV heart disease
• No thromboembolism within the past 6 months

Other

• Chemonaive
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation
• No significant traumatic injury within the past 6 weeks
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to bevacizumab or other study agents
• No active infection
• No psychiatric illness or social situation that would preclude study compliance
• No serious nonhealing wound (including wounds healing by secondary intention), ulcer, or bone fracture

• No CNS disease, including either of the following:

  • Primary brain tumor
  • Seizures not controlled with standard medical therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 8 weeks since prior monoclonal antibody therapy
• No prior bevacizumab

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy)

Surgery

• More than 6 weeks since prior major surgical procedure or open biopsy
• More than 7 days since prior fine needle aspiration or core biopsy
• No concurrent surgery

Other

• Recovered from prior therapy
• At least 3 weeks since prior cytotoxic agents

• No concurrent therapeutic anticoagulation

  • Prophylactic anticoagulation of venous access devices allowed provided PT/INR or PTT criteria are met
• No concurrent chronic aspirin (greater than 325 mg/day) or nonsteroidal anti-inflammatory drugs
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents for the malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Helen X. Chen, MD, NCI - Investigational Drug Branch

Publications and helpful links

General Publications

• Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, Jaffe C, Rubinstein L, Zwiebel J, Kaplan RS. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol. 2006 Jul 20;24(21):3354-60. doi: 10.1200/JCO.2005.05.1573.

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 18, 2013
• Last Verified: April 1, 2004

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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000320506; CTEP-TRC-0301