Temsirolimus and Perifosine in Treating Patients With Recurrent or Progressive Malignant Glioma

PRIMARY OBJECTIVES: I. Define the maximum tolerated dose (MTD) of temsirolimus in combination with perifosine in patients with recurrent or progressive malignant glioma who are not taking enzyme-inducing anti-epileptic drugs (EIAEDs). (Phase I) II. Determine the efficacy of temsirolimus in combination with perifosine in patients with recurrent/progressive glioblastomas (GBMs) not taking EIAEDs as measured by 6 month progression-free survival (6mPFS) and radiographic response rates. (Phase II) SECONDARY OBJECTIVES: I. Characterize the safety profile of perifosine and temsirolimus. II. Estimate median overall and progression-free survival. III. Explore the association of pre-treatment molecular phenotype with response to treatment. IV. Explore molecular effects during treatment including phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (S6K) and rat sarcoma (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) signaling, proliferation, and apoptosis. OUTLINE: This is a phase I dose-escalation study of temsirolimus, followed by a phase II study. PHASE I: Patients receive temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22 and perifosine orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive temsirolimus and perifosine as in phase I. Some patients may also undergo cytoreductive surgery. After completion of study therapy, patients are followed up every 3 months.