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

NCT ID: NCT00062426

Last Updated: 2013-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2003-05-31

Study Completion Date

2011-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colorectal Cancer

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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bevacizumab

Intervention Type BIOLOGICAL

capecitabine

Intervention Type DRUG

fluorouracil

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

oxaliplatin

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prologue Research International

INDUSTRY

Sponsor Role lead

Principal Investigators

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Richard A. Gams, MD

Role: STUDY_CHAIR

Prologue Research International

Lauri Welles, MD

Role:

Sanofi-Synthelabo

Locations

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University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

California Cancer Care, Inc.

Greenbrae, California, United States

Site Status

Valley Tumor Medical Group

Lancaster, California, United States

Site Status

Cancer and Blood Institute of the Desert

Rancho Mirage, California, United States

Site Status

Rocky Mountain Cancer Centers - Midtown

Denver, Colorado, United States

Site Status

Northwestern Connecticut Oncology-Hematology Associates

Torrington, Connecticut, United States

Site Status

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lynn Regional Cancer Center West

Boca Raton, Florida, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Florida Oncology Associates

Jacksonville, Florida, United States

Site Status

Hematology and Oncology Consultants, P.A.

Orlando, Florida, United States

Site Status

Hematology Oncology Associates of theTreasure Coast - Port St. Lucie

Port Saint Lucie, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

Peachtree Hematology and Oncology Consultants, P.C.

Atlanta, Georgia, United States

Site Status

North Idaho Cancer Center

Coeur d'Alene, Idaho, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Lutheran General Cancer Care Center

Park Ridge, Illinois, United States

Site Status

West Suburban Center for Cancer Care

River Forest, Illinois, United States

Site Status

Saint Anthony Medical Center

Rockford, Illinois, United States

Site Status

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Site Status

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Greater Baltimore Medical Center and Cancer Center

Baltimore, Maryland, United States

Site Status

Jackson Oncology Associates, PLLC

Jackson, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Kansas City

Kansas City, Missouri, United States

Site Status

Deaconess Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Cooper Cancer Institute at Cooper University Hospital

Voorhees Township, New Jersey, United States

Site Status

Advanced Oncology Associates

Armonk, New York, United States

Site Status

North Shore Hematology/Oncology Associates, P.C.

East Setauket, New York, United States

Site Status

Arena Oncology Associates

Great Neck, New York, United States

Site Status

St. Vincents Comprehensive Cancer Center

New York, New York, United States

Site Status

New York University Medical Center

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Southeastern Medical Oncology Center

Goldsboro, North Carolina, United States

Site Status

Physicians East - Quadrangle

Greenville, North Carolina, United States

Site Status

Raleigh Hematology/Oncology Associates, P.A. - Wake Practice

Raleigh, North Carolina, United States

Site Status

Hematology Oncology Consultants Inc

Columbus, Ohio, United States

Site Status

Hematology/Oncology of Salem

Salem, Oregon, United States

Site Status

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, United States

Site Status

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Charleston Hematology-Oncology, P.A.

Charleston, South Carolina, United States

Site Status

McCleod Cancer and Blood Center

Johnson City, Tennessee, United States

Site Status

Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

West Clinic

Memphis, Tennessee, United States

Site Status

Sarah Cannon Cancer Center at Centennial Medical Center

Nashville, Tennessee, United States

Site Status

Lone Star Oncology

Austin, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

South Texas Oncology and Hematology

San Antonio, Texas, United States

Site Status

Center for Cancer Prevention and Care at Scott and White Clinic

Temple, Texas, United States

Site Status

Medical Consultants

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21245868 (View on PubMed)

Other Identifiers

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PROLOGUE-SANOFI-ARD5099

Identifier Type: -

Identifier Source: secondary_id

SANOFI-ARD5099

Identifier Type: -

Identifier Source: secondary_id

CDR0000304771

Identifier Type: -

Identifier Source: org_study_id