RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with that of combination chemotherapy in treating patients who have advanced colorectal cancer that has not responded to previous treatment.

Condition	Treatment or Intervention	Phase
Colon Cancer Rectal Cancer	Drug: fluorouracil  Drug: irinotecan  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: chemotherapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall survival of patients with locally advanced, locally recurrent, or metastatic colorectal cancer treated with oxaliplatin, fluorouracil, and leucovorin calcium versus irinotecan, after initial therapy with fluorouracil.
• Determine the time to progression, time to treatment failure, and overall response rate in patients treated with these 2 regimens.
• Determine the toxic effects of these 2 regimens in these patients.
• Compare the quality of life of patients treated with these 2 regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (ECOG 0-1 vs 2), primary indicator lesion (hepatic vs pulmonary vs other), age (less than 65 vs at least 65 years), alkaline phosphatase (less than 2 vs at least 2 times ULN), fluorouracil failure (adjuvant vs metastatic), and membership (intergroup vs expanded participation project).

Patients are randomized to one of two treatment arms:

• Arm I: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience progression or toxicity on the initial regimen may crossover to the other regimen. At least 3 weeks must elapse between regimens.

Quality of life is assessed at baseline, prior to each chemotherapy course, at crossover, and at the end of the study.

Patients are followed every 6 months for 3 years or until death.

PROJECTED ACCRUAL: A total of 560 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
• Progressive disease following:
• One prior fluorouracil based chemotherapy regimen for metastatic disease OR
• Failure during or within 6 months after fluorouracil based adjuvant therapy
• Measurable or evaluable disease
• No CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL (transfusion allowed)

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No uncontrolled high blood pressure
• No unstable angina
• No symptomatic congestive heart failure
• No myocardial infarction with the past 6 months
• No serious uncontrolled cardiac arrhythmias
• No New York Heart Association class III or IV heart disease

Pulmonary:

• No pleural effusion or ascites that cause respiratory compromise (e.g., dyspnea grade 2 or greater)
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Fluent in English
• No active or uncontrolled infection
• No other prior malignancy within the past 5 years, except:
• Adequately treated basal or squamous cell skin cancer
• Adequately treated noninvasive carcinomas
• No sensory neuropathy grade 2 or greater
• No uncontrolled colonic or small bowel disorders (greater than 3 loose stools daily)

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent sargramostim (GM-CSF)

Chemotherapy:

• At least 4 weeks since prior chemotherapy and recovered
• No more than 1 prior chemotherapy regimen for advanced colorectal cancer
• No prior irinotecan or other camptothecin derivative (e.g., topotecan)
• No prior oxaliplatin
• No other concurrent investigational chemotherapy agents

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior major radiotherapy
• No prior radiotherapy to greater than 25% of bone marrow

Surgery:

• At least 4 weeks since prior major surgery and recovered
• At least 2 weeks since prior minor surgery and recovered

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36688,  United States
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock,  Arkansas,  72205,  United States
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
      Veterans Affairs Medical Center - West Los Angeles, Los Angeles,  California,  90073,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States
Florida
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Genesis Medical Center, Davenport,  Iowa,  52804,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      Kansas Cancer Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71130,  United States
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
      Josephine Ford Cancer Center at Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0912,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      CentraCare Health Plaza, Saint Cloud,  Minnesota,  56303,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Jersey
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07019,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Veterans Affairs Medical Center - Albany, Albany,  New York,  12208,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
North Dakota
      Altru Cancer Center, Grand Forks,  North Dakota,  58201,  United States
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428,  United States
Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States
Tennessee
      Danville Radiation Therapy Center, Memphis,  Tennessee,  38104,  United States
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38103,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4095,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - Houston, Houston,  Texas,  77030,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5000,  United States
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Henry Clement Pitot, MD,  Study Chair,  Mayo Clinic Cancer Center   
Philip A. Philip, MD, PhD, FRCP,  Study Chair,  Barbara Ann Karmanos Cancer Institute   
Edith P. Mitchell, MD, FACP,  Study Chair,  Kimmel Cancer Center (KCC)   

Study ID Numbers:  CDR0000067623; NCCTG-N9841; ECOG-N9841; SWOG-N9841
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  April 6, 2000
ClinicalTrials.gov Identifier:  NCT00005036
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08