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Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
This study has been completed.
First Received: October 3, 2003   Last Updated: April 4, 2009   History of Changes
Sponsor: Southwest Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070122
  Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, fluorouracil, and capecitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, 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. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen with bevacizumab works better in treating colorectal cancer.

PURPOSE: This randomized phase III trial is studying giving two different combination chemotherapy regimens together with bevacizumab and comparing how well they work in treating patients with locally advanced, metastatic, or recurrent colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: FOLFOX regimen
Drug: capecitabine
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase III Trial Of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) Or Placebo, As First-Line Therapy In Patients With Previously Untreated Advanced Colorectal Cancer

Resource links provided by NLM:


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

Study Start Date: April 2004
Detailed Description:

OBJECTIVES:

  • Compare overall survival in patients with locally advanced, metastatic, or recurrent colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab vs capecitabine, oxaliplatin, and bevacizumab.
  • Compare progression-free survival and time to treatment failure in patients treated with these regimens.
  • Compare the response of patients with measurable disease treated with these regimens.
  • Compare toxicity rates of these regimens in these patients.
  • Compare patient-reported functional status and convenience of therapy in patients treated with these regimens.
  • Correlate germline polymorphisms of DNA repair (e.g., ERCC-1, XRCC1, GST-P1, XPD, and ribonucleotide reductase), target enzymes (e.g., thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase), angiogenesis (e.g., vascular endothelial growth factor), and growth factors (e.g., epithelial growth factor receptor) with survival, progression-free survival, and toxicity from chemotherapy in patients treated with these regimens.
  • Correlate tumor mRNA expression levels of similar DNA repair enzymes as well as enzymes involved in angiogenesis with survival and progression-free survival in patients treated with these regimens.
  • Correlate tumor mRNA expression levels of similar target enzymes before treatment with survival, progression-free survival, and toxicity in patients treated with these regimens.

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

  • Arm I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.

  • Arm II: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.

Patients are followed every 3 months until disease progression. After disease progression, patients are followed every 6 months for 2 years and then annually for up to 4 years after study entry.

PROJECTED ACCRUAL: A total of 2,200 patients (1,100 per treatment arm) will be accrued for this study within 3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed locally advanced, recurrent, or metastatic colorectal adenocarcinoma

    • Not curable by surgery or amenable to radiotherapy with curative intent
    • Previously resected colorectal cancer with new evidence of metastasis does not require separate histologic or cytologic confirmation unless one of the following is true:

      • More than 5 years has elapsed between primary surgery and development of metastatic disease
      • Primary tumor was T1-T2, N0, M0
  • Site of primary lesion must be or have been in the large bowel as determined by endoscopy, radiology, or surgery
  • Measurable or evaluable disease
  • No known brain or leptomeningeal disease

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • No history of hemorrhagic or thrombotic disorders
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic

  • Bilirubin no greater than 2.0 times upper limit of normal (ULN)
  • SGOT no greater than 2.5 times ULN (5 times ULN for patients with liver involvement)
  • Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN for patients with liver involvement or 10 times ULN for patients with bone involvement)
  • INR no greater than 1.5
  • PTT no greater than ULN

Renal

  • Creatinine no greater than 1.5 times ULN
  • Creatinine clearance at least 50 mL/min
  • Proteinuria less than 1+* OR
  • Protein less than 500mg/24 hours* NOTE: *Proteinuria caused by ureteral stents and not due to nephropathy allowed

Cardiovascular

  • No uncontrolled hypertension

    • Hypertension must be well-controlled (i.e., less than 160/90) and on a stable regimen of antihypertensive therapy
  • No unstable angina
  • No symptomatic congestive heart failure
  • No myocardial infarction within the past 6 months
  • No serious uncontrolled cardiac arrhythmia
  • No New York Heart Association class III or IV heart disease

Pulmonary

  • No symptomatic pulmonary fibrosis

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
  • No active or uncontrolled severe infection
  • No contraindication to oral medications (e.g., severe dysphagia)

    • G-tubes or J-tubes allowed
  • No peripheral neuropathy greater than grade 1
  • No serious non-healing wound, ulcer, or bone fracture
  • No significant traumatic injury within the past 28 days
  • No other severe acute or chronic medical condition or laboratory abnormality that would preclude study participation
  • No psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior bevacizumab

Chemotherapy

  • No prior oxaliplatin
  • No prior chemotherapy for advanced colorectal cancer

    • Prior adjuvant therapy for resected stage II-III disease allowed provided at least 12 months have elapsed between completion of therapy and diagnosis of recurrent disease

Endocrine therapy

  • Not specified

Radiotherapy

  • At least 28 days since prior radiotherapy and recovered

Surgery

  • See Disease Characteristics
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 7 days since prior fine needle aspiration or core biopsy
  • No concurrent major surgery

Other

  • More than 10 days since prior full-dose aspirin (325 mg)
  • No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol)
  • No other concurrent investigational agents
  • No concurrent therapeutic anticoagulation

    • Prophylactic anticoagulation of central venous lines allowed
    • Low-dose prophylactic enoxaparin or heparin allowed
  • No concurrent cimetidine
  • No concurrent sorivudine or its related analogs (e.g., brivudine)
  • No concurrent use of a cold cap or iced mouth rinses
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00070122

  Hide Study Locations
Locations
United States, Alabama
MBCCOP - Gulf Coast
Mobile, Alabama, United States, 36607
United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
CCOP - Western Regional, Arizona
Phoenix, Arizona, United States, 85006-2726
Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
Phoenix, Arizona, United States, 85012
Veterans Affairs Medical Center - Tucson
Tucson, Arizona, United States, 85723
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Veterans Affairs Medical Center - Little Rock (McClellan)
Little Rock, Arkansas, United States, 72205
United States, California
CCOP - Bay Area Tumor Institute
Oakland, California, United States, 94609-3305
CCOP - Santa Rosa Memorial Hospital
Santa Rosa, California, United States, 95403
Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center
Orange, California, United States, 92868
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033
Veterans Affairs Medical Center - Loma Linda (Pettis)
Loma Linda, California, United States, 92357
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Colorado
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80010
Veterans Affairs Medical Center - Denver
Denver, Colorado, United States, 80220
United States, District of Columbia
MBCCOP - Howard University Cancer Center
Washington, District of Columbia, United States, 20060
United States, Florida
Veterans Affairs Medical Center - Tampa (Haley)
Tampa, Florida, United States, 33612
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342-1701
United States, Hawaii
MBCCOP - Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153-5500
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
MBCCOP - University of Illinois at Chicago
Chicago, Illinois, United States, 60612
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
Veterans Affairs Medical Center - Hines (Edward Hines, Junior Hospital)
Hines, Illinois, United States, 60141
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7353
Veterans Affairs Medical Center - Wichita
Wichita, Kansas, United States, 67218
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0084
Veterans Affairs Medical Center - Lexington
Lexington, Kentucky, United States, 40502-2236
United States, Louisiana
Louisiana State University Health Sciences Center - Shreveport
Shreveport, Louisiana, United States, 71130-3932
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
Tulane Cancer Center at Tulane University Hospital and Clinic
New Orleans, Louisiana, United States, 70112
Veterans Affairs Medical Center - New Orleans
New Orleans, Louisiana, United States, 70112
Veterans Affairs Medical Center - Shreveport
Shreveport, Louisiana, United States, 71101-4295
United States, Massachusetts
Cancer Research Center at Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
CCOP - Beaumont
Royal Oak, Michigan, United States, 48073-6769
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
Veterans Affairs Medical Center - Detroit
Detroit, Michigan, United States, 48201-1932
Providence Cancer Institute at Providence Hospital
Southfield, Michigan, United States, 48075
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0912
Veterans Affairs Medical Center - Ann Arbor
Ann Arbor, Michigan, United States, 48105
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
Veterans Affairs Medical Center - Jackson
Jackson, Mississippi, United States, 39216
United States, Missouri
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65807
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
CCOP - St. Louis-Cape Girardeau
Saint Louis, Missouri, United States, 63141
St. Louis University Hospital Cancer Center
Saint Louis, Missouri, United States, 63110
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
United States, New Mexico
MBCCOP - University of New Mexico HSC
Albuquerque, New Mexico, United States, 87131
Veterans Affairs Medical Center - Albuquerque
Albuquerque, New Mexico, United States, 87108-5138
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
United States, North Carolina
CCOP - Southeast Cancer Control Consortium
Goldsboro, North Carolina, United States, 27534-9479
Veterans Affairs Medical Center - Salisbury
Salisbury, North Carolina, United States, 28144
United States, Ohio
CCOP - Columbus
Columbus, Ohio, United States, 43206
CCOP - Dayton
Dayton, Ohio, United States, 45429
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45267-0501
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-9001
Veterans Affairs Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45220-2288
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428-1002
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97201-3098
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Veterans Affairs Medical Center - Portland
Portland, Oregon, United States, 97207
United States, South Carolina
CCOP - Greenville
Greenville, South Carolina, United States, 29615
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Veterans Affairs Medical Center - Charleston
Charleston, South Carolina, United States, 29401-5799
United States, Tennessee
University of Tennessee Cancer Institute
Memphis, Tennessee, United States, 38104
Veterans Affairs Medical Center - Memphis
Memphis, Tennessee, United States, 38104
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234-6200
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Harrington Cancer Center
Amarillo, Texas, United States, 79106
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4095
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0565
Veterans Affairs Medical Center - Amarillo
Amarillo, Texas, United States, 79106
Veterans Affairs Medical Center - Houston
Houston, Texas, United States, 77030
Veterans Affairs Medical Center - San Antonio (Murphy)
San Antonio, Texas, United States, 78229
Veterans Affairs Medical Center - Temple
Temple, Texas, United States, 76504
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112-5550
Veterans Affairs Medical Center - Salt Lake City
Salt Lake City, Utah, United States, 84148
United States, Washington
CCOP - Northwest
Tacoma, Washington, United States, 98405-0986
CCOP - Virginia Mason Research Center
Seattle, Washington, United States, 98101
Puget Sound Oncology Consortium
Seattle, Washington, United States, 98109
Veterans Affairs Medical Center - Seattle
Seattle, Washington, United States, 98108
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Investigator: Charles D. Blanke, MD, FACP OHSU Knight Cancer Institute
Investigator: Heinz-Josef Lenz, MD USC/Norris Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000330000, SWOG-S0303, ECOG-S0303
Study First Received: October 3, 2003
Last Updated: April 4, 2009
ClinicalTrials.gov Identifier: NCT00070122     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the colon
adenocarcinoma of the rectum
stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer
recurrent rectal cancer
recurrent colon cancer

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Colonic Diseases
Physiological Effects of Drugs
Leucovorin
Bevacizumab
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Vitamins
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Micronutrients
Capecitabine
Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Intestinal Diseases
Angiogenesis Inhibitors
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil

ClinicalTrials.gov processed this record on November 27, 2009