A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer
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.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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)
each cycle - 4 weeks; continuous monitoring of AEs
Yes
Jean A Maroun, MD
Principal Investigator
The Ottawa Hospital Regional Cancer Centre
Canada: Health Canada
OTT 06-08
NCT00780169
October 2008
December 2012
Name | Location |
---|