Comparison of Three Chemotherapy Regimens in Treating Patients With Metastatic Colorectal Cancer

Condition(s) targeted: Colorectal Cancer

Intervention: fluorouracil (Drug); leucovorin calcium (Drug); oxaliplatin (Drug); chemotherapy (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
Mace L. Rothenberg, MD, FACP, Study Chair, Affiliation: Vanderbilt-Ingram Cancer Center

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.

Official title: A Multicenter, Open-Label, Randomized, Three-Arm Study Of 5-Fluorouracil (5-FU) Plus Leucovorin (LV) Or Oxaliplatin Or A Combination Of (5-Fu) LV + Oxaliplatin As Second-Line Treatment Of Metastatic Colorectal Carcinoma

Study design: Treatment

Detailed description: 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.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

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

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

Comprehensive Cancer Institute of Huntsville, Huntsville, Alabama 35801, United States

Oncology Center at Providence Park, Mobile, Alabama 36608, United States

Tom Baker Cancer Center - Calgary, Calgary, Alberta T2N 4N2, Canada

University of Alberta, Edmonton, Alberta T6G 2R7, Canada

Arizona Clinical Research Center, Tucson, Arizona 85712, United States

Arkansas Oncology Associates, P.A., Little Rock, Arkansas 72207, United States

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

Kaiser Permanente - Denver, Denver, Colorado 80205, United States

Rocky Mountain Cancer Center, Denver, Colorado 80218, United States

Northwestern Connecticut Oncology-Hematology Associates, Torrington, Connecticut 06790, United States

Lombardi Cancer Center, Washington, District of Columbia 20007, United States

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

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

Cancer Care Center, New Albany, Indiana 47150, United States

Oncology and Hematology Associates, Greenfield, Indiana 46140, United States

Oncology Associates of Cedar Rapids, Cedar Rapids, Iowa 52403, United States

Cancer Center of Kansas - Wichita, Wichita, Kansas 67214, United States

University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

Albert B. Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0084, United States

James Graham Brown Cancer Center, Louisville, Kentucky 40202, United States

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 Center for Cancer Medicine and Blood Disorders, Scarborough, Maine 04074, United States

St. Boniface General Hospital, Winnipeg, Manitoba R2H 2A6, Canada

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Park Nicollet Clinic, St. Louis Park, Minnesota 55416, United States

Parker Hughes Cancer Center, Roseville, Minnesota 55113, United States

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

Cooper Hospital/University Medical Center, Voorhees, New Jersey 08043, United States

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

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

Nova Scotia Cancer Centre, Halifax, Nova Scotia B3H 1V7, Canada

Dayton Oncology/Hematology P.A., Dayton, Ohio 45439, United States

Hematology Oncology Consultants Inc, Columbus, Ohio 43235, United States

Cancer Care Associates, Tulsa, Oklahoma 74136, United States

Naz Medical Center, Midwest City, Oklahoma 73310, United States

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

Willamette Valley Cancer Center, Eugene, Oregon 97401-8122, United States

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

Centre Hospitalier Regional de Rimouski, Rimouski, Quebec G5L 5T1, Canada

Notre Dame Hospital, Montreal, Quebec H4L 2M1, Canada

Saskatoon Cancer Centre, Saskatoon, Saskatchewan S7N 4H4, Canada

Cancer Centers of the Carolinas, Greenville, South Carolina 29605, United States

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

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

Huntsman Cancer Institute, Salt Lake City, Utah 84112, United States

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

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

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

Ivinson Memorial Hospital, Laramie, Wyoming 82070, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2000
Last updated: October 25, 2007