Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated

January 23, 2013 updated by: National Cancer Institute (NCI)

Phase III Trial of Bevacizumab (NSC 704865), Oxaliplatin (NSC 266046), Fluorouracil and Leucovorin Versus Oxaliplatin, Fluorouracil and Leucovorin Versus Bevacizumab Alone in Previously Treated Patients With Advanced Colorectal Cancer

Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bevacizumab in treating patients who have advanced or metastatic colorectal cancer that has been previously treated. 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. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells. It is not yet known if bevacizumab is more effective with or without combination chemotherapy in treating colorectal cancer

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Compare the response, time to progression, and overall survival of patients with previously treated advanced or metastatic colorectal adenocarcinoma treated with oxaliplatin, leucovorin calcium, and fluorouracil with or without bevacizumab versus bevacizumab only. (Arm III closed to accrual as of 03/11/2003).

II. Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to ECOG performance status (0 vs 1 or 2), and prior radiotherapy (yes vs no). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1 and 2.

Arm II: Patients receive oxaliplatin, leucovorin calcium, and 5-FU as in arm I.

Arm III: Patients receive bevacizumab as in arm I. (Arm closed to accrual as of 03/11/2003).

Courses in all arms repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response may receive 2 additional courses.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Type

Interventional

Enrollment (Actual)

880

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Eastern Cooperative Oncology Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the colon or rectum

    • Advanced or metastatic disease
    • Must have received a fluoropyrimidine-based regimen and an irinotecan-based regimen, either alone or in combination, for advanced disease
    • May have relapsed within 6 months of adjuvant therapy with fluorouracil (5-FU) (or combination 5-FU and irinotecan) and progressed after single-agent irinotecan
  • Measurable disease
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No history of thrombotic or hemorrhagic disorders
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST no greater than 5 times ULN
  • INR no greater than 1.5
  • PTT no greater than ULN
  • Creatinine no greater than 1.5 times ULN
  • Proteinuria less than 1+ (i.e., 0 or trace)
  • Protein less than 500 mg by 24-hour urine collection

  • Proteinuria secondary to ureteral stents allowed

    • No proteinuria secondary to nephropathy
  • Controlled hypertension (less than 150/100 mm Hg) allowed if on a stable antihypertensive regimen
  • No prior myocardial infarction
  • No uncontrolled congestive heart failure
  • No unstable angina within the past 3 months
  • No serious nonhealing wound, ulcer, or bone fracture
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior bevacizumab
  • See Disease Characteristics
  • Recovered from prior chemotherapy
  • No prior oxaliplatin
  • At least 2 weeks since prior radiotherapy and recovered
  • At least 28 days since prior major surgical procedure
  • At least 10 days since prior aspirin dose of more than 325 mg/day
  • No concurrent therapeutic anticoagulation except prophylactic anticoagulation of venous access device
  • No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol)
  • No concurrent oral cryotherapy on day 1 of oxaliplatin administration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (bevacizumab, oxaliplatin, leucovorin, fluorouracil)
Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1 and 2.
Biological: bevacizumab
Given IV
Other Names:
  • Avastin
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-FU
  • 5-fluorouracil
  • 5-Fluracil
Experimental: Arm II (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin, leucovorin calcium, and 5-FU as in arm I.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-FU
  • 5-fluorouracil
  • 5-Fluracil
Experimental: Arm III (bevacizumab)
Patients receive bevacizumab as in arm I.
Biological: bevacizumab
Given IV
Other Names:
  • Avastin
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: From the date of entry on study, assessed up to 5 years
From the date of entry on study, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Response defined using RECIST criteria
Time Frame: Up to 5 years
Up to 5 years
Progression free survival
Time Frame: From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, assessed up to 5 years
From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Bruce Giantonio, Eastern Cooperative Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2001

Primary Completion (Actual)

April 1, 2007

Study Registration Dates

First Submitted

October 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 24, 2013

Last Update Submitted That Met QC Criteria

January 23, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02417
  • U10CA021115 (U.S. NIH Grant/Contract)
  • E3200
  • CDR0000068951 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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