A Randomized Phase II Study of Irinotecan, 5-Fluorouracil and Folinic Acid (FOLFIRI) With or Without the Addition of an Endothelin Receptor Antagonist in Patients With Metastatic Colorectal Cancer After Failure of Oxaliplatin-Containing Chemotherapy
OBJECTIVES:
Primary
- To establish the anti-tumor activity of the combination of irinotecan hydrochloride,
fluorouracil, and leucovorin calcium (FOLFIRI) with zibotentan (FOLFERA) as measured by
progression-free survival (time-to-event) in patients with metastatic colorectal cancer
after failure of oxaliplatin-containing chemotherapy.
Secondary
- To determine the toxicity profile of FOLFERA and of maintenance zibotentan in these
patients.
- To determine the feasibility of use of this regimen in these patients.
- To collect tumor and blood samples for future translational work, including
investigating endothelian A receptor (ETAR) expression, k-RAS/b-RAF status and
alterations in relevant pathways such as Akt, MAPK/ERK.
OUTLINE: This is a multicenter study. Patients are stratified according to study site.
Patients are randomized to 1 of 2 treatment arms.
- Arm A: Patients receive irinotecan hydrochloride IV over 1 hour and leucovorin calcium
IV over 2 hours on day 1; fluorouracil IV over 46 hours beginning on day 1; and an oral
placebo tablet once daily on days 1-14. Treatment repeats every 14 days for 12 courses
in the absence of disease progression or unacceptable toxicity. Patients achieving at
least stable disease then receive oral placebo alone once daily in the absence of
disease progression or unacceptable toxicity.
- Arm B: Patients receive irinotecan hydrochloride IV over 2 hours, leucovorin calcium IV
over 2 hours on day 1; fluorouracil IV over 46 hours beginning on day 1; and oral
zibotentan once daily on days 1-14. Treatment repeats every 14 days for 12 courses in
the absence of disease progression or unacceptable toxicity. Patients achieving at
least stable disease then receive oral zibotentan alone once daily in the absence of
disease progression or unacceptable toxicity.
Blood and tissue samples are collected periodically for pharmacogenetic, translational, and
biomarker correlative studies.
After completion of study therapy, patients are followed up at 30 days and then every 12
weeks for up to 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Interventional
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Progression-free survival
No
Anne Thomas, MD
Principal Investigator
University Hospitals, Leicester
Unspecified
CDR0000685062
NCT01205711
April 2010
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