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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00008281
• Other study ID #: CDR0000068394
• Secondary ID: SANOFI-EFC4584BR
• Status: Active, not recruiting
• Phase: Phase 3
• First received: January 6, 2001
• Last updated: January 3, 2014
• Start date: October 2000

Study information

• Verified date: April 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• FOLFOX regimen

• fluorouracil

• leucovorin calcium

• oxaliplatin

Locations

Country	Name	City	State
Canada	Belleville General Hospital	Belleville	Ontario
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Notre Dame Hospital	Montreal	Quebec
Canada	Peterborough Oncology Clinic	Peterborough	Ontario
Canada	Centre Hospitalier Regional de Rimouski	Rimouski	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	Offices of Richard Shapiro, Benjamin Stafford, and Sharon J. Yee	Arcadia	California
United States	Dreyer Medical Clinic	Aurora	Illinois
United States	Lone Star Oncology	Austin	Texas
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Oncology/Hematology Associates - Beaver	Beaver	Pennsylvania
United States	Center for Hematology-Oncology	Boca Raton	Florida
United States	Comprehensive Cancer Care Specialists of Boca Raton	Boca Raton	Florida
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Oncology Associates of Cedar Rapids	Cedar Rapids	Iowa
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Erlanger Health Systems	Chattanooga	Tennessee
United States	Northwestern Medical Faculty Foundation	Chicago	Illinois
United States	Columbia Comprehensive Cancer Care Clinic	Columbia	Missouri
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Hematology Oncology Consultants Inc	Columbus	Ohio
United States	Center for Oncology Research and Treatment, Medical City Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Texas Cancer Center Southwest	Dallas	Texas
United States	Texas Oncology P.A.	Dallas	Texas
United States	Texas Oncology PA (TOPA) at Baylor-Sammons	Dallas	Texas
United States	Dayton Oncology/Hematology P.A.	Dayton	Ohio
United States	Kaiser Permanente - Denver	Denver	Colorado
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Regional Hematology Oncology Associates	Durham	North Carolina
United States	North Shore Hematology/Oncology Associates, P.C.	East Setauket	New York
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Texas Oncology, P.A.	Fort Worth	Texas
United States	Hematology-Oncology Associates of Frederiksburg, Inc.	Fredericksburg	Virginia
United States	University of Florida Health Science Center	Gainesville	Florida
United States	Texas Oncology, P.A.	Garland	Texas
United States	California Cancer Care, Inc.	Greenbrae	California
United States	Oncology and Hematology Associates	Greenfield	Indiana
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Memorial Regional Hospital Comprehensive Cancer Center	Hollywood	Florida
United States	Florida Community Cancer Center	Hudson	Florida
United States	Comprehensive Cancer Institute of Huntsville	Huntsville	Alabama
United States	Hematology/Oncology Associates	Jacksonville	Florida
United States	North Florida Hematology & Oncology Associates	Jacksonville	Florida
United States	Midwest Oncology Consortium	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Baptist Regional Cancer Center - Knoxville	Knoxville	Tennessee
United States	Louisiana Oncology Associates	Lafayette	Louisiana
United States	Lakeland Regional Medical Center	Lakeland	Florida
United States	Ivinson Memorial Hospital	Laramie	Wyoming
United States	Capitol District Hematology Oncology Associates, P.C.	Latham	New York
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Arkansas Oncology Associates, P.A.	Little Rock	Arkansas
United States	Medical Oncology Internal Medicine	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	South Texas Regional Cancer Centers - McAllen	McAllen	Texas
United States	Memphis Cancer Center	Memphis	Tennessee
United States	West Clinic, P.C.	Memphis	Tennessee
United States	Texas Oncology - Mesquite	Mesqutie	Texas
United States	Physicians Office	Metairie	Louisiana
United States	Mount Sinai Comprehensive Cancer Center	Miami	Florida
United States	Oncology-Hematology Group of South Florida	Miami	Florida
United States	Naz Medical Center	Midwest City	Oklahoma
United States	Advanced Health Care	Milwaukee	Wisconsin
United States	Oncology Center at Providence Park	Mobile	Alabama
United States	St. Thomas Medical Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Care Center	New Albany	Indiana
United States	Louisiana State University School of Medicine	New Orleans	Louisiana
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	St. Vincents Comprehensive Cancer Center	New York	New York
United States	Virginia Oncology Associates - Newport News	Newport News	Virginia
United States	Bay Area Tumor Institute	Oakland	California
United States	Ocala Oncology Center	Ocala	Florida
United States	Medical Oncology Care Associates	Orange	California
United States	Office of Thomas A. Marsland	Orange Park	Florida
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Office of Barry S. Berman	Orlando	Florida
United States	P.M.K. Medical Group, Inc.	Oxnard	California
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Hematology-Oncology Associates, PA	Pensacola	Florida
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Hematology/Oncology Associates	Port Saint Lucie	Florida
United States	Raleigh Hematology/Oncology Associates - Wake Practice	Raleigh	North Carolina
United States	Cancer and Blood Institute of the Desert	Rancho Mirage	California
United States	Hematology & Oncology Associates of Virginia	Richmond	Virginia
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	Parker Hughes Cancer Center	Roseville	Minnesota
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	St. John's Mercy Medical Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Baptist Health System Cancer Program	San Antonio	Texas
United States	San Antonio Tumor and Blood Clinic	San Antonio	Texas
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Maine Center for Cancer Medicine and Blood Disorders	Scarborough	Maine
United States	Swedish Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Cancer Care Northwest	Spokane	Washington
United States	Missouri Cancer Care, P.C.	St. Charles	Missouri
United States	Park Nicollet Clinic	St. Louis Park	Minnesota
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	Oncology & Hematology Associates of West Broward	Tamarac	Florida
United States	Office of Ron D. Schiff	Tampa	Florida
United States	Hematology and Oncology Consultants	Titusville	Florida
United States	Northwestern Connecticut Oncology-Hematology Associates	Torrington	Connecticut
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Cancer Care Associates	Tulsa	Oklahoma
United States	Tyler Cancer Center	Tyler	Texas
United States	New York Medical College	Valhalla	New York
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	Northwest Cancer Specialists	Vancouver	Washington
United States	Cooper Hospital/University Medical Center	Voorhees	New Jersey
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	UW Cancer Center Wausau Hospital	Wausau	Wisconsin
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Piedmont Hematology-Oncology Associates-Triad	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,