First Line Infusional 5-Fluorouracil, Folinic Acid and Oxaliplatin for Metastatic Colorectal Cancer or Loco-Regional Recurrency - Role of Chronomodulated Delivery Upon Survival - A Multicenter Randomized Phase III Trial
OBJECTIVES: I. Compare the effects of chronomodulated versus nonchronomodulated infusional
administration of a 3 drug high-dose chemotherapy regimen on survival in patients with
locoregionally recurrent or metastatic colorectal cancer. II. Assess the antitumor effect of
the combination of fluorouracil, leucovorin calcium, and oxaliplatin given as first line
chemotherapy in these patients. III. Assess the response rate and toxicity of this treatment
in these patients. IV. Assess the quality of life of patients receiving this treatment.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
performance status (ECOG 0-1 vs 2), extent of liver involvement (none vs less than 25% vs
25% or greater), and institution. Patients are randomized into 2 arms: Arm I
(chronotherapy): Patients receive a 4 day infusion of fluorouracil, leucovorin calcium, and
oxaliplatin administered via pump using chronomodulated delivery rates. Arm II (fixed
infusion rate): Patients receive leucovorin calcium and oxaliplatin as 2 hour concurrent
infusions followed by fluorouracil as a 22 hour infusion on day 1. On day 2, patients
receive a 2 hour infusion of leucovorin calcium followed by a 22 hour infusion of
fluorouracil. For patients on both arms, courses repeat every 2 weeks until the occurrence
of disease progression, severe toxicity, or complete remission for a minimum of 4 months.
Quality of life is assessed prior to treatment and 2 weeks after courses 4 and 8. Patients
are followed for survival.
PROJECTED ACCRUAL: A total of 554 patients will be accrued for this study.
Allocation: Randomized, Primary Purpose: Treatment
Francis Levi, MD, PhD
Institut de Cancerologie et D'Immunogenetique at Hopital Paul-Brousse
United States: Federal Government