Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer
RATIONALE: Drugs used in chemotherapy such as irinotecan, capecitabine, leucovorin, and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of colorectal cancer by stopping blood flow to the tumor. It is not yet known which combination chemotherapy regimen with or without celecoxib is more effective in treating metastatic colorectal cancer.
PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens and celecoxib to see how well they work compared to two combination chemotherapy regimens alone in treating patients with metastatic colorectal cancer.
Drug: FOLFIRI regimen
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||Irinotecan Combined With Infusional 5-FU/Folinic Acid or Capecitabine and the Role of Celecoxib in Patients With Metastatic Colorectal Cancer|
|Study Start Date:||May 2003|
|Primary Completion Date:||January 2005 (Final data collection date for primary outcome measure)|
- Compare the progression-free survival of patients with metastatic colorectal cancer treated with capecitabine and irinotecan vs fluorouracil, leucovorin calcium, and irinotecan with vs without celecoxib.
- Compare the safety of these regimens in these patients.
- Compare the response rate in patients treated with these regimens.
- Compare the time to treatment failure and overall survival of patients treated with these regimens.
OUTLINE: This is a randomized, double-blind*, multicenter study. Patients are stratified according to participating center, prior adjuvant therapy (yes vs no), and risk group (poor vs intermediate vs good). Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive irinotecan IV over 30-90 minutes on days 1 and 22; oral capecitabine twice daily on days 1-15 and 22-36; and oral celecoxib twice daily on days 1-42.
- Arm II: Patients receive irinotecan and capecitabine as in arm I and oral placebo twice daily on days 1-42.
- Arm III: Patients receive irinotecan IV over 30-90 minutes on days 1, 15, and 29; leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1, 2, 15, 16, 29, and 30; and oral celecoxib twice daily on days 1-42.
- Arm IV: Patients receive irinotecan, CF, and 5-FU as in arm III and oral placebo twice daily on days 1-42.
In all arms, treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. If all chemotherapy is discontinued due to toxicity, patients may continue celecoxib or placebo until disease progression, unacceptable toxicity, or starting a new cytotoxic regimen.
NOTE: *The double-blind treatment only applies to the celecoxib and placebo randomization
Patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 692 patients (173 per treatment arm) will be accrued for this study within 3.5 years.
|Ziekenhuis Network Antwerpen Middelheim|
|Antwerp, Belgium, 2020|
|Academisch Ziekenhuis der Vrije Universiteit Brussel|
|Brussels, Belgium, 1090|
|Institut Jules Bordet|
|Brussels, Belgium, 1000|
|Universitair Ziekenhuis Antwerpen|
|Edegem, Belgium, B-2650|
|Cazk Groeninghe - Campus St-Niklaas|
|Kortrijk, Belgium, B-8500|
|St. Elizabeth Ziekenhuis|
|Turnhout, Belgium, 2300|
|National Cancer Institute - Cairo|
|Charite - Campus Charite Mitte|
|Berlin, Germany, D-10117|
|Celle, Germany, 29223|
|Universitatsklinikum Carl Gustav Carl Carus|
|Dresden, Germany, D-01307|
|Kliniken Essen - Mitte|
|Essen, Germany, D-45136|
|Klinikum der J.W. Goethe Universitaet|
|Frankfurt, Germany, D-60590|
|Klinikum der Albert - Ludwigs - Universitaet Freiburg|
|Freiburg, Germany, D-79106|
|Allgemeines Krankenhaus Hagen|
|Hagen, Germany, D-58095|
|Allgemeines Krankenhaus Altona|
|Hamburg, Germany, 22763|
|Hamburg, Germany, D-20246|
|St. Marien Hospital|
|Hamm, Germany, 59065|
|Kaiserslautern, Germany, D-67653|
|Landau, Germany, D-76829|
|Onkologische Schwerpunktpraxis Leer|
|Leer, Germany, D-26789|
|Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg|
|Magdeburg, Germany, D-39120|
|Meissen, Germany, D-01662|
|Klinikum Rechts Der Isar - Technische Universitaet Muenchen|
|Munich, Germany, D-81675|
|Eberhard Karls Universitaet|
|Tuebingen, Germany, D-72076|
|Wuerzburg, Germany, D-97080|
|National Institute of Oncology|
|Budapest, Hungary, 1122|
|Rambam Medical Center|
|Haifa, Israel, 31096|
|Wolfson Medical Center|
|Holon, Israel, 58100|
|Study Chair:||Claus-Henning Koehne, MD||Klinikum Oldenburg|