Irinotecan Hydrochloride, Fluorouracil, and Leucovorin Calcium With or Without Zibotentan in Treating Patients With Metastatic Colorectal Cancer (FOLFERA)
RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Zibotentan may be effective in treating metastatic colorectal cancer that has not responded to oxaliplatin. It is not yet known whether combination chemotherapy is more effective when given with or without zibotentan in treating metastatic colorectal cancer.
PURPOSE: This randomized phase II trial is studying giving irinotecan hydrochloride together with fluorouracil and leucovorin calcium to see how well it works when given with or without zibotentan in treating patients with metastatic colorectal cancer.
Drug: FOLFIRI regimen
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||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|
- Progression-free survival [ Designated as safety issue: No ]
- Tolerability (side effects) and feasibility of use (number of participants requiring dose delays or reductions and/or treatment withdrawal) [ Designated as safety issue: Yes ]
- Objective response rate as assessed by RECIST criteria [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
|Study Start Date:||April 2010|
|Study Completion Date:||September 2012|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
- 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.
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01205711
|Leicester Royal Infirmary|
|Leicester, England, United Kingdom, LE1 5WW|
|Centre for Cancer Research and Cell Biology at Queen's University Belfast|
|Belfast, Northern Ireland, United Kingdom, BT9 7AB|
|Wales Cancer Trials Unit|
|Cardiff, Wales, United Kingdom, CF11 9LJ|
|Velindre Cancer Center at Velindre Hospital|
|Cardiff, Wales, United Kingdom, CF14 2TL|
|Principal Investigator:||Anne Thomas, MD||University Hospitals, Leicester|