Full Text View
Tabular View
No Study Results Posted
Related Studies
Fluorouracil and Leucovorin Plus Either Irinotecan or Oxaliplatin With or Without Cetuximab in Treating Patients With Previously Untreated Metastatic Adenocarcinoma of the Colon or Rectum
This study is ongoing, but not recruiting participants.
First Received: February 10, 2004   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00077233
  Purpose

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, irinotecan, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one drug with a monoclonal antibody may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective with or without cetuximab in treating metastatic adenocarcinoma (cancer) of the colon or rectum.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining fluorouracil and leucovorin with either irinotecan or oxaliplatin with or without cetuximab in treating patients who have metastatic cancer of the colon or rectum.


Condition Intervention Phase
Colorectal Cancer
Biological: cetuximab
Drug: FOLFIRI regimen
Drug: FOLFOX regimen
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase III

MedlinePlus related topics: Cancer Colorectal Cancer
Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Irinotecan U 101440E Irinotecan hydrochloride Cetuximab Leucovorin Calcium Folinic acid calcium salt pentahydrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control
Official Title: A Phase III Trial Of Irinotecan /5-FU/ Leucovorin Or Oxaliplatin /5-FU / Leucovorin With And Without Cetuximab (C225) For Patients With Untreated Metastatic Adenocarcinoma Of The Colon or Rectum

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

Study Start Date: January 2004
Detailed Description:

OBJECTIVES:

Primary

  • Compare the survival rate of patients with previously untreated metastatic adenocarcinoma of the colon or rectum treated with fluorouracil and leucovorin calcium with oxaliplatin or irinotecan and with or without cetuximab.

Secondary

  • Determine the level of epidermal growth factor receptor (EGFR) expression in patients treated with these regimens.
  • Determine whether expression of EGFR activity, markers of EGFR activity, and serum levels of insulin-like growth factor-1, C-peptide, and insulin-like growth factor binding protein 3 are independent predictors of response rate, time to tumor progression, and survival of patients treated with these regimens.
  • Correlate specific germline polymorphisms related to chemotherapy metabolism and resistance with treatment-related toxicity, tumor response, time to tumor progression, and survival of patients treated with these regimens.
  • Correlate expression of putative prognostic markers in the tumor with tumor response, time to tumor progression, and survival of patients treated with these regimens.
  • Correlate diet, obesity, physical activity, and other lifestyle habits with treatment-related toxicity, progression-free survival, and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior adjuvant therapy (yes vs no) and prior pelvic radiotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

  • Arm I (FOLFIRI): Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on days 1, 15, 29, and 43 and fluorouracil IV continuously over 46-48 hours beginning on days 1, 15, 29, and 43.
  • Arm II (FOLFIRI and cetuximab): Patients receive FOLFIRI as in arm I and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.
  • Arm III (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on days 1, 15, 29, and 43 and fluorouracil IV continuously over 46-48 hours beginning on days 1, 15, 29, and 43.
  • Arm IV (FOLFOX and cetuximab): Patients receive FOLFOX as in arm III and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.

In all arms, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years and then every 3 months for 3 years.

PROJECTED ACCRUAL: Approximately 2,200 patients (550 per treatment arm) will be accrued for this study within 4.6 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 metastatic colorectal adenocarcinoma

    • Primary site of disease in the large bowel as determined endoscopically, surgically, or radiologically
    • Histologic or cytologic confirmation is not required for recurrent metastatic disease in patients with prior colorectal cancer treated with surgery unless either of the following criteria are met:

      • More than 5 years have elapsed between the prior primary surgery and the development of metastatic disease
      • Primary cancer was stage I
  • Tumor tissue available for epidermal growth factor receptor (EGFR) status analysis
  • No pleural effusion or ascites that causes grade 2 or greater dyspnea
  • No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count ≥ 1,500/mm^3
  • Hemoglobin ≥ 9.0 g/dL (transfusion allowed)
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • AST ≤ 5.0 times upper limit of normal (ULN)
  • Albumin ≥ 2.5 g/dL
  • No evidence of Gilbert's syndrome

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No unstable angina
  • No congestive heart failure
  • No prior myocardial infarction
  • No prior stroke
  • No other significant cardiac disease
  • LVEF ≥ normal by echocardiogram or MUGA

Pulmonary

  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

Neurologic

  • No uncontrolled seizure disorder
  • No Temporarily closed neurological disease
  • No symptomatic sensory peripheral neuropathy grade 2 or greater

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No predisposing uncontrolled colonic or small bowel disorder as evidenced by > 3 watery or soft stools daily at baseline*
  • No known sensitivity to chimerized or murine antibodies, cetuximab or other EGFR inhibitors, or tyrosine kinase inhibitors
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix NOTE: *In patients without a colostomy or ileostomy; patients with a colostomy or ileostomy are eligible at the discretion of the investigator

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy for metastatic colorectal cancer
  • No prior chimerized or murine antibodies
  • No prior cetuximab
  • No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

  • See Radiotherapy
  • More than 12 months since prior chemotherapy
  • No prior chemotherapy for metastatic colorectal cancer
  • No prior irinotecan or oxaliplatin in the adjuvant or metastatic setting
  • No more than 6 months or 4 courses of prior adjuvant chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • No prior endocrine therapy for metastatic colorectal cancer
  • No concurrent hormonal therapy except the following:

    • Steroids for adrenal failure
    • Hormones administered for non-disease-related conditions (e.g., insulin for diabetes)
    • Intermittent use of dexamethasone as an antiemetic

Radiotherapy

  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy for metastatic colorectal cancer
  • No prior radiotherapy to more than 25% of bone marrow
  • Prior standard adjuvant chemoradiotherapy for rectal cancer allowed
  • Prior adjuvant radiotherapy with radiosensitizing chemotherapy allowed
  • No concurrent palliative radiotherapy except whole brain radiotherapy for documented CNS disease

Surgery

  • See Disease Characteristics
  • More than 4 weeks since prior major surgery*
  • More than 2 weeks since prior minor surgery* and recovered
  • No prior surgery for metastatic colorectal cancer NOTE: *Insertion of a vascular device is not considered major or minor surgery

Other

  • At least 4 weeks since prior itraconazole or ketoconazole
  • No other prior treatment for metastatic colorectal cancer
  • No prior EGFR inhibitors
  • No prior tyrosine kinase inhibitors
  • No other concurrent investigational agents
  • No concurrent agents to minimize neurotoxicity of oxaliplatin (e.g., carbamazepine, magnesium, or calcium)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077233

  Hide Study Locations
Locations
United States, Alabama
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
United States, California
Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Naval Medical Center - San Diego
San Diego, California, United States, 92134-3202
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
Lombardi Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Veterans Affairs Medical Center - Washington, DC
Washington, District of Columbia, United States, 20422
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307-5001
United States, Florida
Broward General Medical Center
Fort Lauderdale, Florida, United States, 33316
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Memorial Regional Cancer Center at Memorial Regional Hospital
Hollywood, Florida, United States, 33021
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Illinois
CCOP - Evanston
Evanston, Illinois, United States, 60201
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615-7828
Louis A. Weiss Memorial Hospital
Chicago, Illinois, United States, 60640
MBCCOP - University of Illinois at Chicago
Chicago, Illinois, United States, 60612
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
West Suburban Center for Cancer Care
River Forest, Illinois, United States, 60305
United States, Indiana
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Fort Wayne Medical Oncology and Hematology, Incorporated
Fort Wayne, Indiana, United States, 46885-5099
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1009
United States, Kentucky
Baptist Hospital East - Louisville
Louisville, Kentucky, United States, 40207
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
UMASS Memorial Cancer Center - University Campus
Worcester, Massachusetts, United States, 01655
United States, Michigan
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
Saint Joseph, Michigan, United States, 49085
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
Missouri Baptist Cancer Center
Saint Louis, Missouri, United States, 63131
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Veterans Affairs Medical Center - Columbia (Truman Memorial)
Columbia, Missouri, United States, 65201
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
Veterans Affairs Medical Center - Las Vegas
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
New Hampshire Oncology-Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
United States, New York
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
East Syracuse, New York, United States, 13057
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai Medical Center
New York, New York, United States, 10029
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
North Shore University Hospital
Manhasset, New York, United States, 11030
Queens Cancer Center of Queens Hospital
Jamaica, New York, United States, 11432
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
Cape Fear Valley Health System
Fayetteville, North Carolina, United States, 28302-2000
CCOP - Southeast Cancer Control Consortium
Goldsboro, North Carolina, United States, 27534-9479
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
FirstHealth Moore Regional Hospital
Pinehurst, North Carolina, United States, 28374
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
NorthEast Oncology Associates - Concord
Concord, North Carolina, United States, 28025
Veterans Affairs Medical Center - Asheville
Asheville, North Carolina, United States, 28805
Veterans Affairs Medical Center - Durham
Durham, North Carolina, United States, 27705
Zimmer Cancer Center at New Hanover Regional Medical Center
Wilmington, North Carolina, United States, 28402-9025
United States, Ohio
Arthur G. James Cancer Hospital at Ohio State University
Columbus, Ohio, United States, 43210-1240
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
Lifespan: The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Texas
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-8852
Veterans Affairs Medical Center - Dallas
Dallas, Texas, United States, 75219
United States, Vermont
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States, 05401-3498
United States, Virginia
Martha Jefferson Hospital
Charlottesville, Virginia, United States, 22902
MBCCOP - Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
Roanoke, Virginia, United States, 24014
Virginia Oncology Associates - Norfolk
Norfolk, Virginia, United States, 23502
United States, West Virginia
St. Mary's Medical Center
Huntington, West Virginia, United States, 25701
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Alan P. Venook, MD UCSF Helen Diller Family Comprehensive Cancer Center
Investigator: Charles S. Fuchs, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Venook A, Niedzwiecki D, Hollis D, et al.: Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. [Abstract] J Clin Oncol 24 (Suppl 18): A-3509, 2006.

Study ID Numbers: CDR0000350016, CALGB-80203
Study First Received: February 10, 2004
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00077233     History of Changes
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Irinotecan
Leucovorin
Rectal Diseases
Oxaliplatin
Vitamins
Micronutrients
Vitamin B Complex
Digestive System Neoplasms
Cetuximab
Rectal Neoplasm
Trace Elements
Folinic Acid
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Recurrence
Camptothecin
Carcinoma
Calcium, Dietary
Digestive System Diseases
Rectal Cancer
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Physiological Effects of Drugs
Colonic Diseases
Irinotecan
Leucovorin
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Vitamins
Therapeutic Uses
Micronutrients
Vitamin B Complex
Digestive System Neoplasms
Neoplasms by Histologic Type
Growth Substances
Cetuximab
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Pharmacologic Actions
Intestinal Neoplasms
Camptothecin
Carcinoma
Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on May 14, 2009