Oxaliplatin and Bevacizumab (Avastin™) With Either Fluorouracil and Leucovorin or Capecitabine in Treating Patients With Advanced Colorectal Cancer

November 5, 2013 updated by: Prologue Research International

A Randomized, Prospective Study Comparing Three Regimens Of Eloxatin ™ Plus Fluoropyrimidine For Evaluation Of Safety And Tolerability In First Line Treatment Of Patients With Advanced Colorectal Cancer (Tree Study)

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different combinations may kill more tumor cells. Monoclonal antibodies, such as bevacizumab (Avastin™), can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known which regimen works better in treating advanced colorectal cancer.

PURPOSE: This randomized phase III trial is to see if oxaliplatin and bevacizumab work better when combined with either fluorouracil and leucovorin or capecitabine in treating patients who have metastatic or recurrent colorectal cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the incidence of grade 3 and 4 toxic effects occurring within the first 12 weeks of treatment with 2 different schedules of oxaliplatin, bevacizumab (Avastin™), leucovorin calcium, and fluorouracil or with oxaliplatin, Avastin™, and capecitabine in patients with advanced colorectal cancer.
  • Compare the overall response rate, progression-free survival, and time to treatment failure in patients treated with these regimens.
  • Compare the composite toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive bevacizumab (Avastin™) IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil (5-FU) IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive Avastin™ IV over 30-90 minutes and oxaliplatin IV over 2 hours on days 1 and 15 and leucovorin calcium IV over 10 minutes and 5-FU IV over 3 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Arm III: Patients receive Avastin™ IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month, every 3 months for at least 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 375 patients (125 per treatment arm) will be accrued for this study.

Study Type

Interventional

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
    • Alabama
      • Birmingham, Alabama, United States, 35294-3300
        • University of Alabama at Birmingham Comprehensive Cancer Center
    • Arizona
      • Tucson, Arizona, United States, 85712
        • Arizona Clinical Research Center
    • California
      • Greenbrae, California, United States, 94904-2007
        • California Cancer Care, Inc.
      • Lancaster, California, United States, 93534
        • Valley Tumor Medical Group
      • Rancho Mirage, California, United States, 92270
        • Cancer and Blood Institute of the Desert
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers - Midtown
    • Connecticut
      • Torrington, Connecticut, United States, 06790
        • Northwestern Connecticut Oncology-Hematology Associates
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Cancer Center at Georgetown University Medical Center
    • Florida
      • Boca Raton, Florida, United States, 33428
        • Lynn Regional Cancer Center West
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists
      • Jacksonville, Florida, United States, 32207
        • Florida Oncology Associates
      • Orlando, Florida, United States, 32804
        • Hematology and Oncology Consultants, P.A.
      • Port St. Lucie, Florida, United States, 34952
        • Hematology Oncology Associates of theTreasure Coast - Port St. Lucie
      • West Palm Beach, Florida, United States, 33401
        • Palm Beach Cancer Institute
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Peachtree Hematology and Oncology Consultants, P.C.
    • Idaho
      • Coeur d'Alene, Idaho, United States, 83814
        • North Idaho Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
      • Park Ridge, Illinois, United States, 60068-1270
        • Lutheran General Cancer Care Center
      • River Forest, Illinois, United States, 60305
        • West Suburban Center for Cancer Care
      • Rockford, Illinois, United States, 61108
        • Saint Anthony Medical Center
    • Indiana
      • South Bend, Indiana, United States, 46601
        • CCOP - Northern Indiana CR Consortium
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403-1206
        • Cedar Rapids Oncology Associates
    • Kansas
      • Wichita, Kansas, United States, 67214-3882
        • CCOP - Wichita
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center and Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39202
        • Jackson Oncology Associates, PLLC
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • Veterans Affairs Medical Center - Kansas City
    • Montana
      • Billings, Montana, United States, 59107-5100
        • Deaconess Billings Clinic Cancer Center
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Cooper Cancer Institute at Cooper University Hospital
    • New York
      • Armonk, New York, United States, 10504
        • Advanced Oncology Associates
      • East Setauket, New York, United States, 11733
        • North Shore Hematology/Oncology Associates, P.C.
      • Great Neck, New York, United States, 11021
        • Arena Oncology Associates
      • New York, New York, United States, 10016
        • New York University Medical Center
      • New York, New York, United States, 10011
        • St. Vincents Comprehensive Cancer Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Goldsboro, North Carolina, United States, 27534
        • Southeastern Medical Oncology Center
      • Greenville, North Carolina, United States, 27834
        • Physicians East - Quadrangle
      • Raleigh, North Carolina, United States, 27609-7300
        • Raleigh Hematology/Oncology Associates, P.A. - Wake Practice
    • Ohio
      • Columbus, Ohio, United States, 43235
        • Hematology Oncology Consultants Inc
    • Oregon
      • Salem, Oregon, United States, 97301
        • Hematology/Oncology of Salem
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • Pennsylvania Oncology Hematology Associates
      • Pittsburgh, Pennsylvania, United States, 15232
        • Hillman Cancer Center at University of Pittsburgh Cancer Institute
    • South Carolina
      • Charleston, South Carolina, United States, 29403
        • Charleston Hematology-Oncology, P.A.
    • Tennessee
      • Johnson City, Tennessee, United States, 37604
        • McCleod Cancer and Blood Center
      • Memphis, Tennessee, United States, 38119
        • Memphis Cancer Center
      • Memphis, Tennessee, United States, 38120
        • West Clinic
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Cancer Center at Centennial Medical Center
    • Texas
      • Austin, Texas, United States, 78759
        • Lone Star Oncology
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • San Antonio, Texas, United States, 78207
        • South Texas Oncology And Hematology
      • Temple, Texas, United States, 76508
        • Center for Cancer Prevention and Care at Scott and White Clinic
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215-3690
        • Medical Consultants

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the colon or rectum

    • Metastatic or recurrent disease not amenable to potentially curative treatment

  • At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

    • Histological or cytological confirmation is required for a solitary target lesion
  • No CNS metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • SGPT and SGOT no greater than 3 times ULN

Renal

  • Creatinine no greater than 1.5 times ULN
  • Creatinine clearance at least 30 mL/min

Cardiovascular

  • No myocardial infarction within the past 6 months
  • No clinical evidence of congestive heart failure
  • No unstable coronary artery disease

Pulmonary

  • No interstitial pneumonia
  • No extensive symptomatic fibrosis of the lungs

Gastrointestinal

  • Able to tolerate oral medication
  • No lack of physical integrity of the upper gastrointestinal tract
  • No malabsorption syndrome
  • No swallowing difficulties

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study participation
  • No other concurrent serious illness
  • No uncontrolled infection
  • No other concurrent malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix or any other cancer for which the patient has been off all therapy and in remission for at least 5 years
  • No peripheral neuropathy
  • No hypersensitivity to any of the study drugs or their ingredients
  • No known dihydropyrimidine dehydrogenase deficiency
  • No other medical or psychiatric disorder that would preclude giving informed consent or complying with study

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent prophylactic hematopoietic growth factor therapy
  • No prior bevacizumab (Avastin™)

Chemotherapy

  • At least 6 months since prior adjuvant fluorouracil, leucovorin calcium, and irinotecan
  • No prior oxaliplatin
  • No prior chemotherapy for metastatic or recurrent disease
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No concurrent radiotherapy unless for the control of bone pain

Surgery

  • Recovered from prior surgery
  • No prior organ allografts

Other

  • More than 4 weeks since prior investigational drugs
  • No concurrent iced mouth rinses for the prevention of stomatitis
  • No concurrent cold cap alopecia prevention
  • No concurrent pyridoxine
  • No concurrent sorivudine or chemically-related analogues (e.g., brivudine)
  • No concurrent chronic aspirin, nonsteroidal anti-inflammatory drugs, or warfarin

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
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

Prologue Research International

Investigators

  • Study Chair: Richard A. Gams, MD, Prologue Research International
  • Lauri Welles, MD, Sanofi-Synthelabo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

May 1, 2003

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

June 5, 2003

First Submitted That Met QC Criteria

June 5, 2003

First Posted (Estimate)

June 6, 2003

Study Record Updates

Last Update Posted (Estimate)

November 6, 2013

Last Update Submitted That Met QC Criteria

November 5, 2013

Last Verified

April 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000304771
  • PROLOGUE-SANOFI-ARD5099
  • SANOFI-ARD5099

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.

Subscribe