RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for metastatic colorectal cancer. PURPOSE: Phase III trial to compare the effectiveness of three chemotherapy regimens in treating patients who have metastatic colorectal cancer.

Condition	Treatment or Intervention	Phase
recurrent colon cancer adenocarcinoma of the rectum Stage IV rectal cancer recurrent rectal cancer stage IV colon cancer adenocarcinoma of the colon	Procedure: chemotherapy  Drug: fluorouracil  Drug: leucovorin calcium  Drug: oxaliplatin	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the overall survival of patients with metastatic colorectal carcinoma treated with fluorouracil and leucovorin calcium with vs without oxaliplatin vs oxaliplatin alone. II. Compare the response rate, time to tumor-related symptomatic worsening, time to disease progression, onset and duration of complete and partial responses, and duration of disease stabilization in patients treated with these regimens. III. Determine the safety profile of these regimens in these patients.

PROTOCOL OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to Karnofsky performance status (50-60% vs 70-100%), number of metastatic organs (1 vs 2 or more), and LDH value (up to 1.5 times upper limit of normal (ULN) vs greater than 1.5 times ULN). Patients are randomized to one of three treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 22 hours on days 1 and 2. Arm II: Patients receive oxaliplatin IV over 2 hours on day 1. Arm III: Patients receive oxaliplatin IV concurrently with leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 22 hours on day 1. Leucovorin calcium and fluorouracil are administered alone on day 2 on the same schedule as on day 1. Treatment repeats every 2 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed for 30 days, every 2 weeks for up to 3 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 786 patients (262 per arm) will be accrued for this study within 12 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum that is not amenable to potentially curative therapy (e.g., inoperable metastatic disease)
• At least 1 unidimensionally measurable lesion at least 20 mm in diameter by conventional CT or MRI scan or at least 10 mm in diameter by spiral CT scan
• Progressive disease by CT or MRI scan during or no more than 6 months after the last dose of prior first-line irinotecan, fluorouracil, and leucovorin calcium (Saltz regimen) for metastatic disease

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; One and only 1 prior chemotherapy regimen for metastatic disease consisting of first-line irinotecan, fluorouracil, and leucovorin calcium (Saltz regimen); Prior adjuvant fluorouracil with leucovorin calcium allowed; At least 3 weeks since prior chemotherapy for metastatic disease and recovered; No prior adjuvant irinotecan; No prior oxaliplatin
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to study lesions unless evidence of progressive disease within the radiotherapy port; At least 3 weeks since prior radiotherapy
• Surgery: See Disease Characteristics; At least 4 weeks since prior major surgery and recovered; Prior surgical resection of primary tumor or metastases allowed
• Other: At least 30 days since prior investigational drugs; No other concurrent investigational agents; No other concurrent anti-cancer therapy; No concurrent participation in other investigational trials

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 50-100%
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); AST and ALT no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present); Alkaline phosphatase no greater than 2 times ULN (no greater than 3 times ULN if liver metastases present)
• Renal: Creatinine no greater than 1.5 times ULN
• Cardiovascular: No uncontrolled high blood pressure; No unstable angina, symptomatic congestive heart failure, or serious cardiac arrhythmia; No New York Heart Association class III or IV heart disease; No history of cardiac toxicities with prior fluorouracil and leucovorin calcium; No myocardial infarction within the past 6 months
• Pulmonary: No interstitial pneumonia or extensive and symptomatic fibrosis of the lung
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for 6 months after study; No known dihydropyrimidine dehydrogenase deficiency No allergy to platinum-containing drugs; No history of intolerance to study anti-emetics (e.g., 5-HT3 antagonists); No known peripheral neuropathy (absence of deep tendon reflexes as sole deficiency allowed); No uncontrolled diabetes; No active infection; No other active malignancy originating from primary site other than colon or rectum

Alabama
      Comprehensive Cancer Institute of Huntsville, Huntsville,  Alabama,  35801,  United States
      Oncology Center at Providence Park, Mobile,  Alabama,  36608,  United States
Arizona
      Arizona Clinical Research Center, Tucson,  Arizona,  85712,  United States
Arkansas
      Arkansas Oncology Associates, P.A., Little Rock,  Arkansas,  72207,  United States
California
      Bay Area Tumor Institute, Oakland,  California,  94609,  United States
      California Cancer Care, Inc., Greenbrae,  California,  94904,  United States
      Cancer and Blood Institute of the Desert, Rancho Mirage,  California,  92270,  United States
      Kaiser Permanente Medical Center - Vallejo, Vallejo,  California,  94589,  United States
      Kaiser Permanente-Southern California Permanente Medical Group, San Diego,  California,  92120,  United States
      Medical Oncology Care Associates, Orange,  California,  92668,  United States
      Medical Oncology Internal Medicine, Los Angeles,  California,  90067,  United States
      Offices of Richard Shapiro, Benjamin Stafford, and Sharon J. Yee, Arcadia,  California,  91007-7678,  United States
      P.M.K. Medical Group, Inc., Oxnard,  California,  93030,  United States
Colorado
      Kaiser Permanente - Denver, Denver,  Colorado,  80205,  United States
      Rocky Mountain Cancer Center, Denver,  Colorado,  80218,  United States
Connecticut
      Northwestern Connecticut Oncology-Hematology Associates, Torrington,  Connecticut,  06790,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
Florida
      Center for Hematology-Oncology, Boca Raton,  Florida,  33486,  United States
      Comprehensive Cancer Care Specialists of Boca Raton, Boca Raton,  Florida,  33428,  United States
      Florida Cancer Specialists, Fort Myers,  Florida,  33901,  United States
      Florida Community Cancer Center, Hudson,  Florida,  34667,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Hematology and Oncology Consultants, Titusville,  Florida,  32796,  United States
      Hematology-Oncology Associates, PA, Pensacola,  Florida,  32501,  United States
      Hematology/Oncology Associates, Port Saint Lucie,  Florida,  34952,  United States
      Hematology/Oncology Associates, Jacksonville,  Florida,  32216,  United States
      Lakeland Regional Medical Center, Lakeland,  Florida,  33804,  United States
      Memorial Hospital West, Pembroke Pines,  Florida,  33028,  United States
      Memorial Regional Hospital Comprehensive Cancer Center, Hollywood,  Florida,  33021,  United States
      Mount Sinai Comprehensive Cancer Center, Miami,  Florida,  33140,  United States
      North Florida Hematology & Oncology Associates, Jacksonville,  Florida,  32204,  United States
      Ocala Oncology Center, Ocala,  Florida,  34474,  United States
      Office of Barry S. Berman, Orlando,  Florida,  32806,  United States
      Office of Ron D. Schiff, Tampa,  Florida,  33613,  United States
      Office of Thomas A. Marsland, Orange Park,  Florida,  32073,  United States
      Oncology & Hematology Associates of West Broward, Tamarac,  Florida,  33321,  United States
      Oncology-Hematology Group of South Florida, Miami,  Florida,  33176,  United States
      University of Florida Health Science Center, Gainesville,  Florida,  32610-0296,  United States
Illinois
      Dreyer Medical Clinic, Aurora,  Illinois,  60506,  United States
      Hematology Oncology Associates of Illinois-Highland Park, Highland Park,  Illinois,  60035,  United States
      Lutheran General Cancer Care Center, Park Ridge,  Illinois,  60068,  United States
      Northwestern Medical Faculty Foundation, Chicago,  Illinois,  60611,  United States
Indiana
      Cancer Care Center, New Albany,  Indiana,  47150,  United States
      Oncology and Hematology Associates, Greenfield,  Indiana,  46140,  United States
Iowa
      Oncology Associates of Cedar Rapids, Cedar Rapids,  Iowa,  52403,  United States
Kansas
      Cancer Center of Kansas - Wichita, Wichita,  Kansas,  67214,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      James Graham Brown Cancer Center, Louisville,  Kentucky,  40202,  United States
Louisiana
      Baton Rouge General Medical Center, Baton Rouge,  Louisiana,  70821-2511,  United States
      Louisiana Oncology Associates, Lafayette,  Louisiana,  70506,  United States
      Louisiana State University School of Medicine, New Orleans,  Louisiana,  70112-2822,  United States
      Physicians Office, Metairie,  Louisiana,  70006,  United States
Maine
      Maine Center for Cancer Medicine and Blood Disorders, Scarborough,  Maine,  04074,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
Minnesota
      Park Nicollet Clinic, St. Louis Park,  Minnesota,  55416,  United States
      Parker Hughes Cancer Center, Roseville,  Minnesota,  55113,  United States
Missouri
      Columbia Comprehensive Cancer Care Clinic, Columbia,  Missouri,  65201,  United States
      Midwest Oncology Consortium, Kansas City,  Missouri,  64111,  United States
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States
      Missouri Cancer Associates, Columbia,  Missouri,  65201,  United States
      Missouri Cancer Care, P.C., St. Charles,  Missouri,  63301,  United States
      St. John's Mercy Medical Center, Saint Louis,  Missouri,  63141,  United States
New Jersey
      Cooper Hospital/University Medical Center, Voorhees,  New Jersey,  08043,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
      Capitol District Hematology Oncology Associates, P.C., Latham,  New York,  12110-0610,  United States
      Interlakes Oncology/Hematology PC, Rochester,  New York,  14623,  United States
      New York Medical College, Valhalla,  New York,  10595,  United States
      North Shore Hematology/Oncology Associates, P.C., East Setauket,  New York,  11733,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      St. Vincents Comprehensive Cancer Center, New York,  New York,  10011,  United States
      State University of New York Health Sciences Center - Stony Brook, Stony Brook,  New York,  11790-7775,  United States
      Veterans Affairs Medical Center - Albany, Albany,  New York,  12208,  United States
North Carolina
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Piedmont Hematology-Oncology Associates-Triad, Winston Salem,  North Carolina,  27103,  United States
      Raleigh Hematology/Oncology Associates - Wake Practice, Raleigh,  North Carolina,  27609,  United States
      Regional Hematology Oncology Associates, Durham,  North Carolina,  27704,  United States
Ohio
      Dayton Oncology/Hematology P.A., Dayton,  Ohio,  45439,  United States
      Hematology Oncology Consultants Inc, Columbus,  Ohio,  43235,  United States
Oklahoma
      Cancer Care Associates, Tulsa,  Oklahoma,  74136,  United States
      Naz Medical Center, Midwest City,  Oklahoma,  73310,  United States
Oregon
      Willamette Valley Cancer Center, Eugene,  Oregon,  97401-8122,  United States
Pennsylvania
      Abington Memorial Hospital, Abington,  Pennsylvania,  19001,  United States
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States
      Oncology/Hematology Associates - Beaver, Beaver,  Pennsylvania,  15009,  United States
      Pennsylvania Oncology Hematology Associates, Philadelphia,  Pennsylvania,  19107,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104-4283,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States
South Carolina
      Cancer Centers of the Carolinas, Greenville,  South Carolina,  29605,  United States
Tennessee
      Baptist Regional Cancer Center - Knoxville, Knoxville,  Tennessee,  37901,  United States
      Erlanger Health Systems, Chattanooga,  Tennessee,  37403,  United States
      Memphis Cancer Center, Memphis,  Tennessee,  38119,  United States
      St. Thomas Medical Center, Nashville,  Tennessee,  37205,  United States
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
      West Clinic, P.C., Memphis,  Tennessee,  38117,  United States
Texas
      Baptist Health System Cancer Program, San Antonio,  Texas,  78205,  United States
      Center for Oncology Research and Treatment, Medical City Hospital, Dallas,  Texas,  75230,  United States
      Lone Star Oncology, Austin,  Texas,  78759,  United States
      San Antonio Tumor and Blood Clinic, San Antonio,  Texas,  78217,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      South Texas Regional Cancer Centers - McAllen, McAllen,  Texas,  78503,  United States
      Texas Cancer Center Southwest, Dallas,  Texas,  75235,  United States
      Texas Oncology - Mesquite, Mesqutie,  Texas,  75150,  United States
      Texas Oncology P.A., Dallas,  Texas,  75230-2503,  United States
      Texas Oncology PA (TOPA) at Baylor-Sammons, Dallas,  Texas,  75246,  United States
      Texas Oncology, P.A., Fort Worth,  Texas,  76104,  United States
      Texas Oncology, P.A., Garland,  Texas,  75042,  United States
      Tyler Cancer Center, Tyler,  Texas,  75702,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Virginia
      Hematology & Oncology Associates of Virginia, Richmond,  Virginia,  23226,  United States
      Hematology-Oncology Associates of Frederiksburg, Inc., Fredericksburg,  Virginia,  22401,  United States
      Virginia Oncology Associates - Newport News, Newport News,  Virginia,  23606,  United States
Washington
      Cancer Care Northwest, Spokane,  Washington,  99202,  United States
      Northwest Cancer Specialists, Vancouver,  Washington,  98664,  United States
      Swedish Medical Center, Seattle,  Washington,  98122-4307,  United States
      Virginia Mason Medical Center, Seattle,  Washington,  98111,  United States
Wisconsin
      Advanced Health Care, Milwaukee,  Wisconsin,  53209,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
      UW Cancer Center Wausau Hospital, Wausau,  Wisconsin,  54401,  United States
Wyoming
      Ivinson Memorial Hospital, Laramie,  Wyoming,  82070,  United States
Canada, Alberta
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
      University of Alberta, Edmonton,  Alberta,  T6G 2R7,  Canada
Canada, Manitoba
      St. Boniface General Hospital, Winnipeg,  Manitoba,  R2H 2A6,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Belleville General Hospital, Belleville,  Ontario,  K8N 5K5,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
      Peterborough Oncology Clinic, Peterborough,  Ontario,  K9H 7B6,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Centre Hospitalier Regional de Rimouski, Rimouski,  Quebec,  G5L 5T1,  Canada
      Notre Dame Hospital, Montreal,  Quebec,  H4L 2M1,  Canada
Canada, Saskatchewan
      Saskatoon Cancer Centre, Saskatoon,  Saskatchewan,  S7N 4H4,  Canada

Study chairs or principal investigators

Mace L. Rothenberg,  Study Chair,  Sanofi-Synthelabo   

Study ID Numbers:  CDR0000068394; SANOFI-EFC4584; BRCC-00036
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00008281
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08