A Randomized Phase II Study of PEP02 or Irinotecan in Combination With Leucovorin and 5-Flourouracil in Second Line Therapy of Metastatic Colorectal Cancer
- To evaluate the objective response rates (complete response and partial response) in
patients with metastatic colorectal cancer treated with liposome-encapsulated
irinotecan hydrochloride PEP02, leucovorin calcium, and fluorouracil (FUPEP) Versus
irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI 1) or
leucovorin calcium, fluorouracil, and irinotecan hydrochloride-modified (FOLFIRI
- To determine the safety of these regimens in these patients.
- To determine progression-free survival of these patients.
- To determine overall survival of these patients.
- To assess the quality of life of these patients.
- To assess the correlation of UGT1A family polymorphism and the toxicity of
liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride.
OUTLINE: This is a multicenter study. Patients are stratified, in terms of prognosis,
according to treatment center, prognostic score (ECOG performance status [PS] 0 and normal
LDH value vs ECOG PS > 1 and/or LDH > 1 times upper limit of normal), and time to
progression after first-line therapy (≥ 9 months vs < 9 months). Patients are randomized to
1 of 2 treatment arms.
- Arm I: Patients are assigned to either the FOLFIRI 1 or Modified FOLFIRI 3 treatment
groups according to the investigator's discretion.
- FOLFIRI 1: Patients receive irinotecan hydrochloride over 1 hour and leucovorin
calcium IV over 2 hours on day 1 and a bolus of fluorouracil followed by
fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in
the absence of disease progression or unacceptable toxicity
- Modified FOLFIRI 3: Patients receive irinotecan hydrochloride, leucovorin calcium,
and fluorouracil as in FOLFIRI 1. Patients also receive irinotecan hydrochloride
IV over 1 hour on day 3. Courses repeat every 14 days in the absence of disease
progression or unacceptable toxicity.
- Arm II (FUPEP): Patients receive liposome-encapsulated irinotecan hydrochloride PEP02
IV over 60-90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil
IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of
disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacogenetic analysis of UGT1A family
polymorphisms. Quality of life is assessed by using a generic scale EQ-5D and the QLQ-C30
questionnaire at baseline and after courses 4 and 8.
After completion of study treatment, patients are followed up at day 30 and then every 2-3
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Tumor response, in terms of objective response rates (complete response and partial response)
Frederique Maindrault-Goebel, MD
Hopital Saint Antoine