A Modified Phase I/II Trial Of Rapamycin In Patients With Glioblastoma Multiforme
- Determine the maximum tolerated dose of sirolimus in patients with glioblastoma
- Determine the safety profile of this drug in these patients.
- Determine the efficacy of this drug, in terms of 6-month progression-free survival and
objective response, in these patients.
OUTLINE: This is a dose-escalation study.
- Phase I: Patients receive oral sirolimus for 5-7 days before surgery. Patients then
undergo surgical resection. Patients resume oral sirolimus once daily after full
recovery from surgery. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive oral sirolimus as in phase I at the dose determined in that
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for phase I of the study within
3-12 months. A total of 32 patients will be accrued for phase II of the study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (for phase 1)
end of phase 1
Timothy F. Cloughesy, MD
Jonsson Comprehensive Cancer Center
United States: Food and Drug Administration
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|