Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer
The purpose of this study is to assess the safety, the maximum tolerated dose and the recommended dose for phase II studies of a chemotherapy-combination of sorafenib, irinotecan, and 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) as first-line treatment for metastatic colorectal cancer.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer|
- Toxicity spectrum of Sorafenib (MTD, DLT) and the recommended dose (RD) for phase II studies of Sorafenib when combined with FOLFIRI in first line patients with metastatic colorectal cancer (mCRC) [ Time Frame: each cycle - 4 weeks; continuous monitoring of AEs ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of Irinotecan in the presence of Sorafenib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Response according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: every 2 cycles - 8 weeks ] [ Designated as safety issue: No ]
- Time to Progression and Overall Survival [ Time Frame: each cycle - 4 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||October 2008|
|Study Completion Date:||December 2012|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: sorafenib +FOLFIRI
This is a Phase I safety study. There is only one arm of FOLFIRI administered every 14 days (2 week schedule) and sorafenib administered orally, twice daily continuously. First cycle sorafenib began at day +2 to FOLFIRI.
Drug: sorafenib + FOLFIRI
escalating doses of sorafenib and irinotecan
Other Name: sorafenib - Nexavar
A standard phase I dose escalation design with three to six patients per dose level will be used. The first three patients will receive chemotherapy at the dose level 1 for 4 weeks (2 FOLFIRI regimen). The dose will be escalated for the next patients by one dose level if none of the three patients at a dose level experience a dose-limiting toxicity (DLT) during the first six weeks. Intrapatient dose escalation is not allowed. If one of the three patients has a DLT, an additional three patients will be enrolled at this dose level and the dose will be escalated if no additional patients experience a DLT. Otherwise, the dose escalation will be stopped, and the last dose will be regarded as the Maximum Administered Dose (MAD). The preceding dose level will be declared the Maximum Tolerated Dose (MTD). This dose level will be the recommended dose (RD). At least 6 patients will be treated at the MTD. The cohort at the MTD dose level can be expanded to as many as 12 patients to gain experience with the toxicities and efficacy of Sorafenib + FOLFIRI combination over a broad patient range. Patients experiencing a DLT during the first cycle of treatment will have the drug withheld. They will be eligible for repeated treatment at a lower dose or treated off protocol.
Treatment is to be discontinued in cases of serious or unmanageable toxicity or request by the patient. Otherwise therapy will continue until clinically or radiologically documented disease progression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00780169
|The Ottawa Hospital Cancer Centre|
|Ottawa, Ontario, Canada, K1H 8L6|
|Principal Investigator:||Jean A Maroun, MD||The Ottawa Hospital Regional Cancer Centre|