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| Sponsor: | Sanofi-Aventis |
|---|---|
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00008281 |
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer |
Drug: FOLFOX regimen Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin |
Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment |
| 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 Start Date: | October 2000 |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Hide Study Locations| United States, Alabama | |
| Comprehensive Cancer Institute of Huntsville | |
| Huntsville, Alabama, United States, 35801 | |
| Oncology Center at Providence Park | |
| Mobile, Alabama, United States, 36608 | |
| United States, Arizona | |
| Arizona Clinical Research Center | |
| Tucson, Arizona, United States, 85712 | |
| United States, Arkansas | |
| Arkansas Oncology Associates, P.A. | |
| Little Rock, Arkansas, United States, 72207 | |
| United States, California | |
| Kaiser Permanente Medical Center - Vallejo | |
| Vallejo, California, United States, 94589 | |
| California Cancer Care, Inc. | |
| Greenbrae, California, United States, 94904 | |
| Cancer and Blood Institute of the Desert | |
| Rancho Mirage, California, United States, 92270 | |
| Bay Area Tumor Institute | |
| Oakland, California, United States, 94609 | |
| Kaiser Permanente-Southern California Permanente Medical Group | |
| San Diego, California, United States, 92120 | |
| Medical Oncology Care Associates | |
| Orange, California, United States, 92668 | |
| Medical Oncology Internal Medicine | |
| Los Angeles, California, United States, 90067 | |
| Offices of Richard Shapiro, Benjamin Stafford, and Sharon J. Yee | |
| Arcadia, California, United States, 91007-7678 | |
| P.M.K. Medical Group, Inc. | |
| Oxnard, California, United States, 93030 | |
| United States, Colorado | |
| Kaiser Permanente - Denver | |
| Denver, Colorado, United States, 80205 | |
| Rocky Mountain Cancer Center | |
| Denver, Colorado, United States, 80218 | |
| United States, Connecticut | |
| Northwestern Connecticut Oncology-Hematology Associates | |
| Torrington, Connecticut, United States, 06790 | |
| United States, District of Columbia | |
| Lombardi Cancer Center | |
| Washington, District of Columbia, United States, 20007 | |
| United States, Florida | |
| Center for Hematology-Oncology | |
| Boca Raton, Florida, United States, 33486 | |
| Comprehensive Cancer Care Specialists of Boca Raton | |
| Boca Raton, Florida, United States, 33428 | |
| Florida Cancer Specialists | |
| Fort Myers, Florida, United States, 33901 | |
| Florida Community Cancer Center | |
| Hudson, Florida, United States, 34667 | |
| Florida Hospital Cancer Institute | |
| Orlando, Florida, United States, 32804 | |
| Hematology and Oncology Consultants | |
| Titusville, Florida, United States, 32796 | |
| Hematology-Oncology Associates, PA | |
| Pensacola, Florida, United States, 32501 | |
| Hematology/Oncology Associates | |
| Port Saint Lucie, Florida, United States, 34952 | |
| Office of Barry S. Berman | |
| Orlando, Florida, United States, 32806 | |
| Lakeland Regional Medical Center | |
| Lakeland, Florida, United States, 33804 | |
| Memorial Hospital West | |
| Pembroke Pines, Florida, United States, 33028 | |
| Memorial Regional Hospital Comprehensive Cancer Center | |
| Hollywood, Florida, United States, 33021 | |
| Mount Sinai Comprehensive Cancer Center | |
| Miami, Florida, United States, 33140 | |
| North Florida Hematology & Oncology Associates | |
| Jacksonville, Florida, United States, 32204 | |
| Ocala Oncology Center | |
| Ocala, Florida, United States, 34474 | |
| Hematology/Oncology Associates | |
| Jacksonville, Florida, United States, 32216 | |
| Office of Ron D. Schiff | |
| Tampa, Florida, United States, 33613 | |
| Office of Thomas A. Marsland | |
| Orange Park, Florida, United States, 32073 | |
| Oncology & Hematology Associates of West Broward | |
| Tamarac, Florida, United States, 33321 | |
| Oncology-Hematology Group of South Florida | |
| Miami, Florida, United States, 33176 | |
| University of Florida Health Science Center | |
| Gainesville, Florida, United States, 32610-0296 | |
| United States, Illinois | |
| Northwestern Medical Faculty Foundation | |
| Chicago, Illinois, United States, 60611 | |
| Hematology Oncology Associates of Illinois-Highland Park | |
| Highland Park, Illinois, United States, 60035 | |
| Lutheran General Cancer Care Center | |
| Park Ridge, Illinois, United States, 60068 | |
| Dreyer Medical Clinic | |
| Aurora, Illinois, United States, 60506 | |
| United States, Indiana | |
| Cancer Care Center | |
| New Albany, Indiana, United States, 47150 | |
| Oncology and Hematology Associates | |
| Greenfield, Indiana, United States, 46140 | |
| United States, Iowa | |
| Oncology Associates of Cedar Rapids | |
| Cedar Rapids, Iowa, United States, 52403 | |
| United States, Kansas | |
| Cancer Center of Kansas - Wichita | |
| Wichita, Kansas, United States, 67214 | |
| University of Kansas Medical Center | |
| Kansas City, Kansas, United States, 66160-7357 | |
| United States, Kentucky | |
| Albert B. Chandler Medical Center, University of Kentucky | |
| Lexington, Kentucky, United States, 40536-0084 | |
| James Graham Brown Cancer Center | |
| Louisville, Kentucky, United States, 40202 | |
| United States, Louisiana | |
| Baton Rouge General Medical Center | |
| Baton Rouge, Louisiana, United States, 70821-2511 | |
| Louisiana Oncology Associates | |
| Lafayette, Louisiana, United States, 70506 | |
| Louisiana State University School of Medicine | |
| New Orleans, Louisiana, United States, 70112-2822 | |
| Physicians Office | |
| Metairie, Louisiana, United States, 70006 | |
| United States, Maine | |
| Maine Center for Cancer Medicine and Blood Disorders | |
| Scarborough, Maine, United States, 04074 | |
| United States, Michigan | |
| Barbara Ann Karmanos Cancer Institute | |
| Detroit, Michigan, United States, 48201-1379 | |
| United States, Minnesota | |
| Park Nicollet Clinic | |
| St. Louis Park, Minnesota, United States, 55416 | |
| Parker Hughes Cancer Center | |
| Roseville, Minnesota, United States, 55113 | |
| United States, Missouri | |
| Columbia Comprehensive Cancer Care Clinic | |
| Columbia, Missouri, United States, 65201 | |
| Midwest Oncology Consortium | |
| Kansas City, Missouri, United States, 64111 | |
| Missouri Baptist Cancer Center | |
| Saint Louis, Missouri, United States, 63131 | |
| Missouri Cancer Associates | |
| Columbia, Missouri, United States, 65201 | |
| Missouri Cancer Care, P.C. | |
| St. Charles, Missouri, United States, 63301 | |
| St. John's Mercy Medical Center | |
| Saint Louis, Missouri, United States, 63141 | |
| United States, New Jersey | |
| Cooper Hospital/University Medical Center | |
| Voorhees, New Jersey, United States, 08043 | |
| United States, New York | |
| Albert Einstein Comprehensive Cancer Center | |
| Bronx, New York, United States, 10461 | |
| Capitol District Hematology Oncology Associates, P.C. | |
| Latham, New York, United States, 12110-0610 | |
| Interlakes Oncology/Hematology PC | |
| Rochester, New York, United States, 14623 | |
| New York Medical College | |
| Valhalla, New York, United States, 10595 | |
| North Shore Hematology/Oncology Associates, P.C. | |
| East Setauket, New York, United States, 11733 | |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | |
| New York, New York, United States, 10016 | |
| Roswell Park Cancer Institute | |
| Buffalo, New York, United States, 14263-0001 | |
| St. Vincents Comprehensive Cancer Center | |
| New York, New York, United States, 10011 | |
| State University of New York Health Sciences Center - Stony Brook | |
| Stony Brook, New York, United States, 11790-7775 | |
| Veterans Affairs Medical Center - Albany | |
| Albany, New York, United States, 12208 | |
| United States, North Carolina | |
| Lineberger Comprehensive Cancer Center, UNC | |
| Chapel Hill, North Carolina, United States, 27599-7295 | |
| Piedmont Hematology-Oncology Associates-Triad | |
| Winston-Salem, North Carolina, United States, 27103 | |
| Raleigh Hematology/Oncology Associates - Wake Practice | |
| Raleigh, North Carolina, United States, 27609 | |
| Regional Hematology Oncology Associates | |
| Durham, North Carolina, United States, 27704 | |
| United States, Ohio | |
| Dayton Oncology/Hematology P.A. | |
| Dayton, Ohio, United States, 45439 | |
| Hematology Oncology Consultants Inc | |
| Columbus, Ohio, United States, 43235 | |
| United States, Oklahoma | |
| Cancer Care Associates | |
| Tulsa, Oklahoma, United States, 74136 | |
| Naz Medical Center | |
| Midwest City, Oklahoma, United States, 73310 | |
| United States, Oregon | |
| Willamette Valley Cancer Center | |
| Eugene, Oregon, United States, 97401-8122 | |
| United States, Pennsylvania | |
| Abington Memorial Hospital | |
| Abington, Pennsylvania, United States, 19001 | |
| Kimmel Cancer Center of Thomas Jefferson University - Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19107-5541 | |
| Oncology/Hematology Associates - Beaver | |
| Beaver, Pennsylvania, United States, 15009 | |
| Pennsylvania Oncology Hematology Associates | |
| Philadelphia, Pennsylvania, United States, 19107 | |
| University of Pennsylvania Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19104-4283 | |
| University of Pittsburgh Cancer Institute | |
| Pittsburgh, Pennsylvania, United States, 15213-3489 | |
| United States, South Carolina | |
| Cancer Centers of the Carolinas | |
| Greenville, South Carolina, United States, 29605 | |
| United States, Tennessee | |
| Baptist Regional Cancer Center - Knoxville | |
| Knoxville, Tennessee, United States, 37901 | |
| Erlanger Health Systems | |
| Chattanooga, Tennessee, United States, 37403 | |
| Memphis Cancer Center | |
| Memphis, Tennessee, United States, 38119 | |
| St. Thomas Medical Center | |
| Nashville, Tennessee, United States, 37205 | |
| Vanderbilt-Ingram Cancer Center | |
| Nashville, Tennessee, United States, 37232-6838 | |
| West Clinic, P.C. | |
| Memphis, Tennessee, United States, 38117 | |
| United States, Texas | |
| Baptist Health System Cancer Program | |
| San Antonio, Texas, United States, 78205 | |
| Simmons Cancer Center - Dallas | |
| Dallas, Texas, United States, 75235-9154 | |
| Lone Star Oncology | |
| Austin, Texas, United States, 78759 | |
| San Antonio Tumor and Blood Clinic | |
| San Antonio, Texas, United States, 78217 | |
| Center for Oncology Research and Treatment, Medical City Hospital | |
| Dallas, Texas, United States, 75230 | |
| South Texas Regional Cancer Centers - McAllen | |
| McAllen, Texas, United States, 78503 | |
| Texas Cancer Center Southwest | |
| Dallas, Texas, United States, 75235 | |
| Texas Oncology - Mesquite | |
| Mesqutie, Texas, United States, 75150 | |
| Texas Oncology P.A. | |
| Dallas, Texas, United States, 75230-2503 | |
| Texas Oncology PA (TOPA) at Baylor-Sammons | |
| Dallas, Texas, United States, 75246 | |
| Texas Oncology, P.A. | |
| Fort Worth, Texas, United States, 76104 | |
| Texas Oncology, P.A. | |
| Garland, Texas, United States, 75042 | |
| Tyler Cancer Center | |
| Tyler, Texas, United States, 75702 | |
| United States, Utah | |
| Huntsman Cancer Institute | |
| Salt Lake City, Utah, United States, 84112 | |
| United States, Virginia | |
| Hematology & Oncology Associates of Virginia | |
| Richmond, Virginia, United States, 23226 | |
| Hematology-Oncology Associates of Frederiksburg, Inc. | |
| Fredericksburg, Virginia, United States, 22401 | |
| Virginia Oncology Associates - Newport News | |
| Newport News, Virginia, United States, 23606 | |
| United States, Washington | |
| Cancer Care Northwest | |
| Spokane, Washington, United States, 99202 | |
| Northwest Cancer Specialists | |
| Vancouver, Washington, United States, 98664 | |
| Swedish Medical Center | |
| Seattle, Washington, United States, 98122-4307 | |
| Virginia Mason Medical Center | |
| Seattle, Washington, United States, 98111 | |
| United States, Wisconsin | |
| Advanced Health Care | |
| Milwaukee, Wisconsin, United States, 53209 | |
| University of Wisconsin Comprehensive Cancer Center | |
| Madison, Wisconsin, United States, 53792-6164 | |
| UW Cancer Center Wausau Hospital | |
| Wausau, Wisconsin, United States, 54401 | |
| United States, Wyoming | |
| Ivinson Memorial Hospital | |
| Laramie, Wyoming, United States, 82070 | |
| Canada, Alberta | |
| Tom Baker Cancer Center - Calgary | |
| Calgary, Alberta, Canada, T2N 4N2 | |
| University of Alberta | |
| Edmonton, Alberta, Canada, T6G 2R7 | |
| Canada, Manitoba | |
| St. Boniface General Hospital | |
| Winnipeg, Manitoba, Canada, R2H 2A6 | |
| Canada, Nova Scotia | |
| Nova Scotia Cancer Centre | |
| Halifax, Nova Scotia, Canada, B3H 1V7 | |
| Canada, Ontario | |
| Belleville General Hospital | |
| Belleville, Ontario, Canada, K8N 5K5 | |
| Cancer Care Ontario-London Regional Cancer Centre | |
| London, Ontario, Canada, N6A 4L6 | |
| Mount Sinai Hospital - Toronto | |
| Toronto, Ontario, Canada, M5G 1X5 | |
| Peterborough Oncology Clinic | |
| Peterborough, Ontario, Canada, K9H 7B6 | |
| Princess Margaret Hospital | |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Toronto Sunnybrook Regional Cancer Centre | |
| Toronto, Ontario, Canada, M4N 3M5 | |
| Canada, Quebec | |
| Centre Hospitalier Regional de Rimouski | |
| Rimouski, Quebec, Canada, G5L 5T1 | |
| Notre Dame Hospital | |
| Montreal, Quebec, Canada, H4L 2M1 | |
| Canada, Saskatchewan | |
| Saskatoon Cancer Centre | |
| Saskatoon, Saskatchewan, Canada, S7N 4H4 | |
| Study Chair: | Mace L. Rothenberg, MD, FACP | Vanderbilt-Ingram Cancer Center |
More Information
| Study ID Numbers: | CDR0000068394, SANOFI-EFC4584, BRCC-00036 |
| Study First Received: | January 6, 2001 |
| Last Updated: | January 10, 2009 |
| ClinicalTrials.gov Identifier: | NCT00008281 History of Changes |
| Health Authority: | United States: Federal Government |
|
stage IV colon cancer stage IV rectal cancer recurrent colon cancer |
recurrent rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum |
|
Antimetabolites Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Immunologic Factors Gastrointestinal Diseases Antineoplastic Agents Colonic Diseases Physiological Effects of Drugs Leucovorin Rectal Diseases Oxaliplatin Neoplasms by Site Therapeutic Uses Vitamins |
Micronutrients Digestive System Neoplasms Vitamin B Complex Growth Substances Intestinal Diseases Immunosuppressive Agents Intestinal Neoplasms Pharmacologic Actions Neoplasms Digestive System Diseases Fluorouracil Gastrointestinal Neoplasms Colorectal Neoplasms |