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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00025337
First received: October 11, 2001
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Adenocarcinoma of the Colon
Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage III Colon Cancer
Stage III Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Biological: bevacizumab
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Time Frame: From the date of entry on study, assessed up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response defined using RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 880
Study Start Date: September 2001
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • 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-fluorouracil
  • 5-Fluracil
  • 5-FU
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-fluorouracil
  • 5-Fluracil
  • 5-FU
Experimental: Arm III (bevacizumab)
Patients receive bevacizumab as in arm I.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00025337

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Bruce Giantonio Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025337     History of Changes
Other Study ID Numbers: NCI-2012-02417, E3200, U10CA021115, CDR0000068951
Study First Received: October 11, 2001
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Antibodies, Monoclonal
Fluorouracil
Calcium, Dietary
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 22, 2014