Sirolimus in Treating Patients With Glioblastoma Multiforme
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Rapamycin; Surgery; Supportive Care
Intervention type(s): Drug; Procedure; Procedure
Intervention description(s): 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.
Other intervention name(s): Sirolimus
Intervention MeSH terms: Sirolimus
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult brain tumor; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma