The purpose of this study is to test the effectiveness of perifosine in preventing further tumor growth using the established optimal dose of the drug. A second goal is to determine if perifosine can block the molecules in the tumor that drive it to divide and grow.

This is a phase II study of the small molecule inhibitor perifosine (NSC 639966, D21266, KRX-0401) in the treatment of patients with recurrent glioblastoma multiforme (GBM) and other recurrent malignant gliomas. The goal of the phase II study is to determine efficacy as measured by the progressionfree survival rate after 6 months of treatment. Secondary goals include determination of molecular and metabolic effects of perifosine by tissue analysis and PET imaging.

In addition, when cytoreductive surgery is recommended as part of the standard of care at study entry, patients will be considered for a "surgical arm." In this case, patients will receive perifosine for 5-10 days before surgery during which tumor will be aliquoted both for diagnostic purposes and for molecular effects of the drug in vivo and for analysis of drug penetration into tumor tissue.

Inclusion Criteria:

• Patients must have shown unequivocal evidence for tumor progression by MRI or CT scan.
• Patients must be on a stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI and PET scans.
• Patients must have failed prior radiation therapy.
• Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery (including gamma-knife or cyber-knife) must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, and/or MR spectroscopy, and/or MR Perfusion, and/or surgical documentation of disease.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.
• Age > 18 years old, and with a life expectancy > 8 weeks.
• Karnofsky Performance Status ≥ 50%
• Patients must have recovered from all acute toxicities from prior therapies. At least 28 days must have elapsed since prior radiation.
• Patients must have adequate bone marrow function
• Patients must agree to practice adequate contraception.

Exclusion Criteria:

• Patients must not be taking EIAEDs
• Patients must not have any significant medical illnesses or other history that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• Patients must not have active infection or serious intercurrent medical illness.
• HIV-Positive patients receiving combination anti-retroviral therapy are excluded from the study due to possible retro-viral drug interactions.
• Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.

1 year