Clinical trial NCT00008281: Comparison of Three Chemotherapy Regimens in Treating Patients With 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-02-16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

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