RATIONALE: Chemotherapy drugs such as sirolimus use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase I/II trial to study the effectiveness of sirolimus in treating patients who have glioblastoma multiforme that did not respond to previous radiation therapy.
OBJECTIVES: * Determine the maximum tolerated dose of sirolimus in patients with glioblastoma multiforme. * 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 phase. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Phase 1: Initial dose 6mg on day 1 and then 2mg each day for 5-7 days before surgery. No dosing during surgery recovery. After recorvery 6mg loading dose on day 1 then 2mg each day. Cycle is every 4 weeks. Dose escalation: Level 2: 15mg load/5mg/day, Level 3: 30mg load/10mg/day, Level 4: 45mg load/15mg/day. Phase 2: Will utilize dose established in phase I. Dosing schedule will remain the same.
Surgical resection.
Corticosteroids should be used in smallest dose to control symptoms of cerebral edema and mass effect. Anti-seizure medications should be used as indicated. Febrile neutropenia may be managed according to local institution's infectious disease guidelines. If neurosurgical management is required for reasons not due to tumor progression, these procedures must be documented.
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States
Maximum tolerated dose (for phase 1)
Time frame: end of phase 1
Efficacy in terms of progression-free survival at 6 months and objective response (phase II)
Time frame: 6 months after last subject finishes trial
Safety Profile (phase I)
Time frame: end of phase I
Further evaluate safety profile
Time frame: end of phase II
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.