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. PURPOSE: Randomized phase II trial to study the effectiveness of combining fluorouracil and leucovorin with or without oxaliplatin in treating patients who have recurrent 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 II

Further Study Details: 

OBJECTIVES: I. Compare the overall response rate and overall survival of patients with recurrent metastatic colorectal adenocarcinoma treated with third-line therapy comprising fluorouracil and leucovorin calcium with or without oxaliplatin. II. Compare the onset and duration of complete and partial responses and duration of disease stabilization in patients treated with these regimens. III. Compare the proportion of patients with stable disease and proportion of patients with tumor-related symptomatic improvement treated with these regimens. IV. Compare the time to disease progression and time to tumor-related symptomatic worsening in patients treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 2-4 minutes followed by fluorouracil IV continuously over 22 hours on days 1 and 2. Arm II: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 2-4 minutes followed by fluorouracil IV continuously over 22 hours on day 1. On day 2, patients receive leucovorin calcium and fluorouracil as in arm I. Treatment in both arms repeats every 2 weeks for at least 1 year in the absence of disease progression. Patients are followed at day 30 and then for approximately 6 months.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum; Metastatic/recurrent disease not amenable to potentially curative therapy (e.g., inoperable metastatic disease)
• Documented sequential disease progression (by CT or MRI scan) after 2 prior chemotherapy regimens for metastatic/recurrent disease
• At least 1 unidimensionally measurable lesion At least 20 mm by conventional CT or MRI scan OR At least 10 mm by spiral CT scan
• Must have received prior fluorouracil (or capecitabine) and leucovorin calcium with or without irinotecan as first-line therapy and irinotecan with or without fluorouracil (or capecitabine) and leucovorin calcium as second-line therapy for metastatic disease

--Prior/Concurrent Therapy--

• Biologic therapy: No prior anticancer biologic therapy
• Chemotherapy: See Disease Characteristics; No prior oxaliplatin; No prior adjuvant irinotecan; Prior adjuvant fluorouracil and leucovorin calcium allowed; At least 3 weeks since prior chemotherapy (e.g., second-line irinotecan with or without fluorouracil (or capecitabine) and leucovorin calcium) for metastatic disease and recovered
• Endocrine therapy: Not specified
• Radiotherapy: At least 3 weeks since prior radiotherapy; No prior radiotherapy to target lesion unless documented progression within the radiation portal
• Surgery: See Disease Characteristics; At least 4 weeks since prior surgery for primary tumor or metastases and recovered
• Other: No prior investigational anticancer drug; No other concurrent investigational agents

--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); SGOT and SGPT no greater than 2 times ULN (6 times ULN if documented liver metastases present); Alkaline phosphatase no greater than 2 times ULN (6 times ULN if documented liver metastases present)
• Renal: Creatinine no greater than 1.5 times ULN
• Cardiovascular: No New York Heart Association class III or IV symptomatic congestive heart failure; No serious cardiac arrhythmia; No unstable angina; No myocardial infarction within the past 6 months
• Pulmonary: No interstitial pneumonia; No 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 peripheral neuropathy (absence of deep tendon reflexes as the sole neurologic abnormality allowed); No diabetes or active infection; No known dihydropyrimidine dehydrogenase deficiency

Arizona
      Arizona Clinical Research Center, Tucson,  Arizona,  85712,  United States
Arkansas
      Arkansas Cancer Clinic, P.A., Pine Bluff,  Arkansas,  71603,  United States
California
      California Cancer Care, Inc., Greenbrae,  California,  94904,  United States
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Citrus Valley Medical Center, Covina,  California,  92807,  United States
      Comprehensive Cancer Centers of the Desert, Palm Springs,  California,  92262,  United States
      John Muir Medical Center, Walnut Creek,  California,  94598,  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
      Kenmar Research Institute, Los Angeles,  California,  90057,  United States
Colorado
      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
      Florida Cancer Specialists, Fort Myers,  Florida,  33901,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Halifax Medical Center, Daytona Beach,  Florida,  32114,  United States
      Hematology/Oncology Associates, Port Saint Lucie,  Florida,  34952,  United States
      Hematology/Oncology Associates, Jacksonville,  Florida,  32216,  United States
      Lake Heart and Cancer Medical Center, Leesburg,  Florida,  34748,  United States
      Oncology-Hematology Group of South Florida, Miami,  Florida,  33176,  United States
Illinois
      Cancer Care Specialists of Central Illinois, S.C., Decatur,  Illinois,  62526,  United States
      Dreyer Medical Clinic, Aurora,  Illinois,  60506,  United States
      Northwest Medical Specialists, P.C., Arlington Heights,  Illinois,  60004,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
Indiana
      Hope Center, Terre Haute,  Indiana,  47809,  United States
Iowa
      Medical Oncology and Hematology Associates, Des Moines,  Iowa,  50309,  United States
      Mercy Cancer Center, Mason City,  Iowa,  50401,  United States
Kentucky
      James Graham Brown Cancer Center, Louisville,  Kentucky,  40202,  United States
      Lucille Parker Markey Cancer Center, University of Kentucky, Lexington,  Kentucky,  40536-0093,  United States
Louisiana
      Baton Rouge General Medical Center, Baton Rouge,  Louisiana,  70821-2511,  United States
      Cancer and Blood Institute, Metairie,  Louisiana,  70006,  United States
Massachusetts
      Saints Memorial Medical Center, Lowell,  Massachusetts,  01852,  United States
Michigan
      Saint Joseph Mercy Hospital, Ann Arbor,  Michigan,  48106,  United States
Mississippi
      Jackson Oncology Associates, PLLC, Jackson,  Mississippi,  39202,  United States
      Medical Oncology Group, Gulfport,  Mississippi,  39501,  United States
Missouri
      St. Joseph Oncology, Inc., Saint Joseph,  Missouri,  64506,  United States
Montana
      Deaconess Billings Clinic, Billings,  Montana,  59107-5100,  United States
New Jersey
      Central Jersey Oncology Center, New Brunswick,  New Jersey,  08901,  United States
      Hematology Associates of New Jersey, P.A., Ridgewood,  New Jersey,  07450,  United States
      Jersey Shore Cancer Center, Neptune,  New Jersey,  07753,  United States
      Monmouth Hematology-Oncology Associates, P.A., West Long Branch,  New Jersey,  07764,  United States
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States
New Mexico
      University of New Mexico Cancer Research & Treatment Center, Albuquerque,  New Mexico,  87131,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
      HemOnCare, P.C., Brooklyn,  New York,  11235,  United States
      Interlakes Oncology/Hematology PC, Rochester,  New York,  14623,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      New York Medical College, Valhalla,  New York,  10595,  United States
      New York University Medical Center, New York,  New York,  10016,  United States
      North Shore Hematology/Oncology Associates, P.C., East Setauket,  New York,  11733,  United States
      Reddy Cancer Treatment Center, Malone,  New York,  12953,  United States
      South Shore Hematology Oncology Associates, P.C., Rockville Centre,  New York,  11570,  United States
      University of Rochester Medical Center, Rochester,  New York,  14642,  United States
Ohio
      Hematology Oncology Consultants Inc, Columbus,  Ohio,  43235,  United States
      Lawrence M. Stallings Medical Practice, Wooster,  Ohio,  44691,  United States
      Mid-Ohio Oncology/Hematology, Inc., Columbus,  Ohio,  43213,  United States
Oklahoma
      Oklahoma Oncology Inc., Tulsa,  Oklahoma,  74104,  United States
Oregon
      Bend Memorial Clinic, Bend,  Oregon,  97701,  United States
      Salem Hospital Regional Cancer Center, Salem,  Oregon,  97309-5014,  United States
Pennsylvania
      Oncology Hematology of Lehigh Valley, P.C., Bethlehem,  Pennsylvania,  18015,  United States
      Pennsylvania Oncology Hematology Associates, Philadelphia,  Pennsylvania,  19107,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
Tennessee
      Baptist Regional Cancer Center, Knoxville,  Tennessee,  37920,  United States
      Family Cancer Center, Collierville,  Tennessee,  38017,  United States
      Memorial Hospital Cancer Center - Chattanooga, Chattanooga,  Tennessee,  37404,  United States
      West Cancer Clinic, Memphis,  Tennessee,  38120,  United States
Texas
      Cancer Therapy and Research Center, San Antonio,  Texas,  78229,  United States
      Center for Oncology Research and Treatment, Medical City Hospital, Dallas,  Texas,  75230,  United States
      Scott and White Memorial Hospital, Temple,  Texas,  76508,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
      Intermountain Hematology/Oncology Associates, Inc., Salt Lake City,  Utah,  84124,  United States
Washington
      Seattle Cancer Care Alliance, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

Richard Alan Gams,  Study Chair,  Prologue Research International   

Study ID Numbers:  CDR0000068606; PROLOGUE-EFC4760; SANOFI-EFC4760
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00016198
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08