Interracial Study of CPT-11 (Irinotecan) Pharmacokinetics in 5-Fluorouracil Refractory Colorectal Cancer: A Population Pharmacokinetic/Pharmacodynamic Study of CPT-11
- Determine the interracial differences in the pharmacokinetics of irinotecan in
combination with fluorouracil in terms of SN-38 glucuronidation and biliary index, and
gastrointestinal (GI) toxicity in patients with metastatic, locally advanced, or
recurrent colorectal cancer.
- Determine if there is a significant relationship between UGT1A1 genotype (promoter
and/or coding region mutation) and CYP3A4 promoter genotype, vs GI toxicity, bone
marrow toxicity, and pharmacokinetics of irinotecan in this patient population.
OUTLINE: Patients are stratified according to race (Asian or Pacific Islander vs black vs
Hispanic vs white).
Patients receive irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV
on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for a total of 5 courses in the
absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 400 patients (100 per stratum) will be accrued for this study
within 3 years.
Primary Purpose: Treatment
Brian Leyland-Jones, MD
McGill Cancer Centre at McGill University
United States: Federal Government