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 if irinotecan is more effective with or without oxaliplatin in treating metastatic colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with or without oxaliplatin in treating patients who have metastatic colorectal cancer.

Condition	Treatment or Intervention	Phase
stage IV colon cancer Stage IV rectal cancer recurrent colon cancer recurrent rectal cancer	Drug: irinotecan  Drug: oxaliplatin  Procedure: chemotherapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall survival of patients with metastatic colorectal cancer treated with irinotecan with or without oxaliplatin.
• Compare the response rate, time to tumor-related worsening of symptoms, time to disease progression, onset and duration of responses, and duration of disease stabilization in these patients treated with these regimens.
• Compare the safety of these regimens in these patients.

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 involved (1 vs 2 or more), lactic dehydrogenase (no greater than 1.5 times upper limit of normal (ULN) vs greater than 1.5 times ULN), and prior fluorouracil chemotherapy (adjuvant vs first-line treatment for metastatic disease). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive irinotecan IV over 90 minutes on day 1.
• Arm II: Patients receive oxaliplatin IV over 120 minutes followed by irinotecan IV over 30 minutes on day 1. Courses repeat in each arm every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days, every 4 weeks for 3 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 596 patients (298 per arm) will be accrued for this study within 18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Metastatic or recurrent disease that is not amenable to potentially curative treatment
• Progressive or recurrent disease during or after 1, and only 1, regimen of fluorouracil with or without leucovorin calcium or during or within 6 months after adjuvant chemotherapy with fluorouracil and leucovorin calcium

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/SGPT 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 5 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No New York Heart Association class III or IV congestive heart failure
• No serious cardiac arrhythmia
• No history of cardiac toxicity from fluorouracil/leucovorin calcium
• No myocardial infarction within past 6 months

Pulmonary:

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

Other:

• No uncontrolled predisposing colonic or small bowel disorder
• No prior chronic enteropathy, chronic diarrhea, or unresolved bowel obstruction/subobstruction
• No diabetes
• No active infection
• No known current peripheral neuropathy
• No concurrent active cancer except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No intolerance of appropriate antiemetics
• No history of anaphylaxis or potential intolerance to atropine sulfate or loperamide
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No prior irinotecan or oxaliplatin
• No other prior chemotherapy agents except fluorouracil with or without leucovorin calcium as first-line therapy for metastatic disease or in the adjuvant setting

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy to non-target lesions allowed
• No prior radiotherapy to target lesions unless disease progression is documented within the radiation port
• At least 3 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior major surgical procedure and recovered
• Prior surgery for primary tumor or metastasis allowed

Other:

• At least 30 days since prior investigational drug
• No concurrent investigational agents

Alabama
      Comprehensive Cancer Institute of Huntsville, Huntsville,  Alabama,  35801,  United States
      Oncology Center at Providence Park, Mobile,  Alabama,  36688,  United States
Arizona
      Arizona Clinical Research Center, Tucson,  Arizona,  85712,  United States
California
      Los Angeles,  California,  90067,  United States
      California Cancer Care, Inc., Greenbrae,  California,  94904-2007,  United States
      Cancer and Blood Institute of the Desert, Rancho Mirage,  California,  92270,  United States
      Citrus Valley Medical Center, Covina,  California,  91722,  United States
      John Wayne Cancer Institute, Santa Monica,  California,  90404,  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
      Medical Oncology Care Associates, Orange,  California,  92868,  United States
      P.M.K. Medical Group, Inc., Oxnard,  California,  93030,  United States
      Tower Hematology Oncology Medical Group, Los Angeles,  California,  90048,  United States
Colorado
      Colorado Permanente Medical Group, P.C., Denver,  Colorado,  80205,  United States
      Rocky Mountain Cancer Center, Denver,  Colorado,  80218,  United States
      University of Colorado Cancer Center, Denver,  Colorado,  80220,  United States
Connecticut
      Whittingham Cancer Center, Norwalk,  Connecticut,  06856,  United States
District of Columbia
      George Washington University Medical Center, Washington,  District of Columbia,  20037,  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
      Hematology and Oncology Associates of Jacksonville, Jacksonville,  Florida,  32207,  United States
      Hematology and Oncology Consultants, Titusville,  Florida,  32796,  United States
      Hematology and Oncology Consultants, P.A., Orlando,  Florida,  32804,  United States
      Hematology/Oncology Associates, Port Saint Lucie,  Florida,  34952,  United States
      Lake Heart and Cancer Medical Center, Leesburg,  Florida,  34748,  United States
      Lakeland Regional Medical Center, Lakeland,  Florida,  33804,  United States
      Oncology & Hematology Associates of West Broward, Tamarac,  Florida,  33321,  United States
      Oncology-Hematology Group of South Florida, Miami,  Florida,  33176,  United States
      Shands Hospital and Clinics, University of Florida, Gainesville,  Florida,  32610-100277,  United States
      Southeast Florida Hematology-Oncology Group, Fort Lauderdale,  Florida,  33308,  United States
      University Community Hospital, Tampa,  Florida,  33613,  United States
      University of Florida Health Science Center - Jacksonville, Jacksonville,  Florida,  32209,  United States
Idaho
      North Idaho Cancer Center, Coeur D Alene,  Idaho,  83814,  United States
Illinois
      Dreyer Medical Clinic, Aurora,  Illinois,  60506,  United States
      Northwest Medical Specialists, P.C., Arlington Heights,  Illinois,  60004,  United States
      Northwestern Medical Faculty Foundation, Chicago,  Illinois,  60611,  United States
Indiana
      Cancer Care Center, New Albany,  Indiana,  47150,  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
      Kentuckiana Cancer Institute, Louisville,  Kentucky,  40202,  United States
      Norton Healthcare Pavilion, Louisville,  Kentucky,  40202,  United States
      Veterans Affairs Medical Center - Louisville, Louisville,  Kentucky,  40206,  United States
Louisiana
      Baton Rouge General Medical Center, Baton Rouge,  Louisiana,  70806,  United States
      Doctors Hospital of Jefferson, Metairie,  Louisiana,  70006,  United States
      Louisiana Oncology Associates, Lafayette,  Louisiana,  70506,  United States
      Stanley Scott Cancer Center, New Orleans,  Louisiana,  70112,  United States
Maryland
      Greater Baltimore Medical Center and Cancer Center, Baltimore,  Maryland,  21204,  United States
Massachusetts
      Berkshire Hematology Oncology, P.C., Pittsfield,  Massachusetts,  01201,  United States
      Medical Center of Boston, Boston,  Massachusetts,  02120,  United States
Michigan
      Flint,  Michigan,  48532,  United States
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
Minnesota
      Parker Hughes Cancer Center, Roseville,  Minnesota,  55113,  United States
Mississippi
      Jackson Oncology Associates, PLLC, Jackson,  Mississippi,  39202,  United States
Missouri
      Missouri Cancer Care, P.C., St. Charles,  Missouri,  63301,  United States
      Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
      St. John's Mercy Medical Center, Saint Louis,  Missouri,  63141,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      Great Falls Clinic, Great Falls,  Montana,  59405,  United States
      Western Montana Clinic, Missoula,  Montana,  59807-7609,  United States
New Jersey
      Cooper Cancer Institute, Voorhees,  New Jersey,  08043,  United States
      Somerset Medical Center, Somerville,  New Jersey,  08876,  United States
New York
      Interlakes Oncology/Hematology PC, Rochester,  New York,  14623,  United States
      Montefiore Medical Center, Bronx,  New York,  10467-2490,  United States
      New York Medical College, Valhalla,  New York,  10595,  United States
      Queens Hospital Center, Jamaica,  New York,  11432,  United States
      Queens Medical Associates, PC, Fresh Meadows,  New York,  11365,  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, Winston Salem,  North Carolina,  27103,  United States
      Raleigh Hematology/Oncology Associates - Wake Practice, Raleigh,  North Carolina,  27609,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      Hematology Oncology Consultants Inc, Columbus,  Ohio,  43235,  United States
Oregon
      Bend Memorial Clinic, Bend,  Oregon,  97701,  United States
      Kaiser Permanente - Portland, Portland,  Oregon,  97227,  United States
Pennsylvania
      Abington Hematology Oncology Associates, Incorporated, Meadowbrook,  Pennsylvania,  18974,  United States
      Pennsylvania Oncology Hematology Associates, Philadelphia,  Pennsylvania,  19106,  United States
      Pinnacle Health Hospitals, Harrisburg,  Pennsylvania,  17105-8700,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
South Carolina
      Cancer Centers of the Carolinas, Greenville,  South Carolina,  29615,  United States
      Physicians East - Quadrangle, Greenville,  South Carolina,  27834,  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
      Tennessee Oncology, P.L.L.C., Nashville,  Tennessee,  37205,  United States
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6307,  United States
      West Clinic, 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
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States
      Hematology-Oncology Associates of Frederiksburg, Inc., Fredericksburg,  Virginia,  22401,  United States
Washington
      Virginia Mason Medical Center, Seattle,  Washington,  98101,  United States
Wisconsin
      Advanced Health Care, Milwaukee,  Wisconsin,  53209,  United States
      UW Cancer Center Wausau Hospital, Wausau,  Wisconsin,  54401,  United States
Wyoming
      Irving Cancer Center, Laramie,  Wyoming,  82070,  United States
Brazil
      Hospital do Cancer A C Comargo, Sao Paulo,  CEP: 01509-010,  Brazil
      Hospital Erastos Gaertner, Curitiba-PR,  CEP: 81520-060,  Brazil
      Hospital Joao Alves Fiho, Aracaiu-SE,  CEP: 49094-970,  Brazil
      Hospital Socor, Belo Horizonte MG,  CEP: 30180-060,  Brazil
      Instituto Nacional de Cancer, Rio de Janeiro,  20230-130,  Brazil
      Oncologistas Associados, Rio de Janeiro,  CEP: 22260-020,  Brazil
Brazil, Rio Grande do Sul
      Porto Alegre Hospital, Porto Alegre,  Rio Grande do Sul,  90035-003,  Brazil
Brazil, Sao Paulo
      Instituto de Oncologia de Soracaba, Sorocaba,  Sao Paulo,  18030-200,  Brazil
Canada
      Zoom International Incoporated, St. Jerome Quebec,  JYZ 5T3,  Canada
Canada, Alberta
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
      University of Alberta, Edmonton,  Alberta,  T6G 2R7,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
      Northeastern Ontario Regional Cancer Centre, Sudbury, Sudbury,  Ontario,  P3E 5J1,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Royal Victoria Hospital, Barrie, Barrie,  Ontario,  L4M 6M2,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Centre Hospitalier de L'Universitaire de Quebec, Pavillon CHUL, Sainte-Foy,  Quebec,  GIV 4G2,  Canada
      Centre Hospitalier Universitaire de Quebec, Quebec City,  Quebec,  G1R 2J6,  Canada
      Cite de la Sante de Laval, Laval,  Quebec,  H7M 3L9,  Canada
      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada
      Hopital Du Sacre-Coeur de Montreal, Montreal,  Quebec,  H4J 1C5,  Canada
      Jewish General Hospital - Montreal, Montreal,  Quebec,  H3T 1E2,  Canada
      L'Hopital Laval, Ste Foy,  Quebec,  G1V 4G5,  Canada
      L'Hotel Dieu de Levis, Levis,  Quebec,  G6V 3Z1,  Canada
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
Canada, Saskatchewan
      Saskatoon Cancer Centre, Saskatoon,  Saskatchewan,  S7N 4H4,  Canada
Czech Republic
      Centre of Clinical Oncology and Radiation Oncology, Ceske Budejovice,  370 01,  Czech Republic
      Charles University Hospital, HRADEC KRALOVE,  500 02,  Czech Republic
      Fakultni Nemocnice V Motole, Praha,  150 06,  Czech Republic
      Onkologicka Klinka A Onkologicka Lab, Prague,  128 08,  Czech Republic
Hungary
      Debreceni Egyetem Onkologiai Tanzek, Debrecen,  H-4012,  Hungary
      Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia, Budapest,  H-1032,  Hungary
      Kozponti Honvedkorhaz I. Belgyogyaszat, Budapest,  H-1134,  Hungary
      National Institute of Oncology, Budapest,  1125,  Hungary
      Petz Aladar County Hospital, Gydr,  h-9024,  Hungary
      Semmelweis University, Budapest,  1082,  Hungary
      Szent Laszlo Korhaz, Budapest,  H-1097,  Hungary
Poland
      Institute of Oncology, Lodz,  93509,  Poland
      Jagiellonian University, Krakow (Cracow),  31-826,  Poland
      Maria S. Curie Memorial Institute, Gliwice,  44-101,  Poland
      Wielkopolskie Centrum Onkologii Oddzial Chemioterapii, Poznan,  61-866,  Poland
United Kingdom, England
      Charing Cross Hospital, London,  England,  W6 8RF,  United Kingdom
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom
      Derriford Hospital, Plymouth,  England,  PL6 8DH,  United Kingdom
      Guy's and St. Thomas' Hospitals NHS Trust, London,  England,  SE1 9RT,  United Kingdom
      Maidstone Hospital, Maidstone,  England,  ME16 9QQ,  United Kingdom
      Royal Marsden Hospital, Sutton,  England,  SM2 5PT,  United Kingdom
      St. Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom
      St. Luke's Cancer Center, Guildford,  England,  GU2 5XX,  United Kingdom
      Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom

Study chairs or principal investigators

Daniel G. Haller, MD,  Study Chair,  University of Pennsylvania Cancer Center   

Study ID Numbers:  CDR0000068524; SANOFI-EFC4585
Record last reviewed:  March 2003
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012389
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08