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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Biological: bevacizumab; Drug: capecitabine; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Allocation:	Randomized
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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)
Study Start Date :	May 2003
Actual Study Completion Date :	February 2011

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Prologue Research International

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Leighl NB, Bennouna J, Yi J, Moore N, Hambleton J, Hurwitz H. Bleeding events in bevacizumab-treated cancer patients who received full-dose anticoagulation and remained on study. Br J Cancer. 2011 Feb 1;104(3):413-8. doi: 10.1038/sj.bjc.6606074. Epub 2011 Jan 18.

ClinicalTrials.gov Identifier:	NCT00062426 History of Changes
Other Study ID Numbers:	CDR0000304771; PROLOGUE-SANOFI-ARD5099; SANOFI-ARD5099
First Posted:	June 6, 2003
Last Update Posted:	November 6, 2013
Last Verified:	April 2004

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the colon; adenocarcinoma of the rectum; recurrent colon cancer	stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Bevacizumab; Oxaliplatin; Capecitabine; Fluorouracil	Levoleucovorin; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Antidotes; Protective Agents