Clinical trial NCT00016198: Fluorouracil and Leucovorin With or Without Oxaliplatin in Treating Patients With Recurrent Metastatic Colorectal Cancer
Official title: A Randomized, Multicenter, Phase II Study Of Bolus/Infusion 5-FU/LV (de Gramont Regimen) Versus Oxaliplatin And Bolus/Infusion 5-FU/LV (de Gramont Regimen) As Third-Line Treatment Of Patients With Metastatic Colorectal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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: 2004-01-07
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. Combining more than one drug may kill more tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of combining fluorouracil and leucovorin with or without oxaliplatin in treating patients who have recurrent metastatic colorectal cancer.

Detailed description: OBJECTIVES: I. Compare the overall response rate and overall survival of patients with recurrent metastatic colorectal adenocarcinoma treated with third-line therapy comprising fluorouracil and leucovorin calcium with or without oxaliplatin. II. Compare the onset and duration of complete and partial responses and duration of disease stabilization in patients treated with these regimens. III. Compare the proportion of patients with stable disease and proportion of patients with tumor-related symptomatic improvement treated with these regimens. IV. Compare the time to disease progression and time to tumor-related symptomatic worsening in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 2-4 minutes followed by fluorouracil IV continuously over 22 hours on days 1 and 2. Arm II: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 2-4 minutes followed by fluorouracil IV continuously over 22 hours on day 1. On day 2, patients receive leucovorin calcium and fluorouracil as in arm I. Treatment in both arms repeats every 2 weeks for at least 1 year in the absence of disease progression. Patients are followed at day 30 and then for approximately 6 months.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the colon or rectum Metastatic/recurrent disease not amenable to potentially curative therapy (e.g., inoperable metastatic disease) Documented sequential disease progression (by CT scan or MRI) after 2 prior chemotherapy regimens for metastatic/recurrent disease At least 1 unidimensionally measurable lesion At least 20 mm by conventional CT scan or MRI OR At least 10 mm by spiral CT scan Must have received prior fluorouracil (or capecitabine) and leucovorin calcium with or without irinotecan as first-line therapy and irinotecan with or without fluorouracil (or capecitabine) and leucovorin calcium as second-line therapy 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) SGOT and SGPT no greater than 2 times ULN (6 times ULN if documented liver metastases present) Alkaline phosphatase no greater than 2 times ULN (6 times ULN if documented liver metastases present) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV symptomatic congestive heart failure No serious cardiac arrhythmia No unstable angina No myocardial infarction within the past 6 months Pulmonary: No interstitial pneumonia No 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 peripheral neuropathy (absence of deep tendon reflexes as the sole neurologic abnormality allowed) No diabetes or active infection No known dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior anticancer biologic therapy Chemotherapy: See Disease Characteristics No prior oxaliplatin No prior adjuvant irinotecan Prior adjuvant fluorouracil and leucovorin calcium allowed At least 3 weeks since prior chemotherapy (e.g., second-line irinotecan with or without fluorouracil (or capecitabine) and leucovorin calcium) for metastatic disease and recovered Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy No prior radiotherapy to target lesion unless documented progression within the radiation portal Surgery: See Disease Characteristics At least 4 weeks since prior surgery for primary tumor or metastases and recovered Other: No prior investigational anticancer drug No other concurrent investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Pine Bluff
country: United States
facility: Arkansas Cancer Clinic, P.A.
state: Arkansas
city: Covina
country: United States
facility: Citrus Valley Medical Center
state: California
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Kenmar Research Institute
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Centers 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: Walnut Creek
country: United States
facility: John Muir Medical Center
state: California
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: Center for Hematology-Oncology
state: Florida
city: Daytona Beach
country: United States
facility: Halifax Medical Center
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Hematology/Oncology Associates
state: Florida
city: Leesburg
country: United States
facility: Lake Heart and Cancer Medical Center
state: Florida
city: Miami
country: United States
facility: Oncology-Hematology Group of South Florida
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology/Oncology Associates
state: Florida
city: Arlington Heights
country: United States
facility: Northwest Medical Specialists, P.C.
state: Illinois
city: Aurora
country: United States
facility: Dreyer Medical Clinic
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois, S.C.
state: Illinois
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center
state: Iowa
city: Lexington
country: United States
facility: Lucille Parker Markey Cancer 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: Metairie
country: United States
facility: Cancer and Blood Institute
state: Louisiana
city: Lowell
country: United States
facility: Saints Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Gulfport
country: United States
facility: Medical Oncology Group
state: Mississippi
city: Jackson
country: United States
facility: Jackson Oncology Associates, PLLC
state: Mississippi
city: Saint Joseph
country: United States
facility: St. Joseph Oncology, Inc.
state: Missouri
city: Billings
country: United States
facility: Deaconess Billings Clinic
state: Montana
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore Cancer Center
state: New Jersey
city: New Brunswick
country: United States
facility: Central Jersey Oncology Center
state: New Jersey
city: Ridgewood
country: United States
facility: Hematology Associates of New Jersey, P.A.
state: New Jersey
city: West Long Branch
country: United States
facility: Monmouth Hematology-Oncology Associates, P.A.
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research & Treatment Center
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Comprehensive Cancer Center
state: New York
city: Brooklyn
country: United States
facility: HemOnCare, P.C.
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology/Oncology Associates, P.C.
state: New York
city: Malone
country: United States
facility: Reddy Cancer Treatment Center
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology/Hematology PC
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Rockville Centre
country: United States
facility: South Shore Hematology Oncology Associates, P.C.
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Columbus
country: United States
facility: Mid-Ohio Oncology/Hematology, Inc.
state: Ohio
city: Columbus
country: United States
facility: Hematology Oncology Consultants Inc
state: Ohio
city: Wooster
country: United States
facility: Lawrence M. Stallings Medical Practice
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Oncology Inc.
state: Oklahoma
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Salem
country: United States
facility: Salem Hospital Regional Cancer Center
state: Oregon
city: Bethlehem
country: United States
facility: Oncology Hematology of Lehigh Valley, P.C.
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Chattanooga
country: United States
facility: Memorial Hospital Cancer Center - Chattanooga
state: Tennessee
city: Collierville
country: United States
facility: Family Cancer Center
state: Tennessee
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center
state: Tennessee
city: Memphis
country: United States
facility: West Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: Center for Oncology Research and Treatment, Medical City Hospital
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Hematology/Oncology Associates, Inc.
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Prologue Research International
name: Richard A. Gams, MD
role: STUDY_CHAIR
References: