Perifosine and Torisel (Temsirolimus) for Recurrent/Progressive Malignant Gliomas

Inclusion Criteria:

* Histologically confirmed intracranial glioblastoma (GBM), including sub variants
* At least 15 unstained slides or at least 1 tissue blocks must be collected from at least one prior surgery.
* Received prior radiotherapy and prior temozolomide as treatment for the malignant glioma
* Recovered from toxic effects of prior therapies and at least 2 weeks must have elapsed since any prior signaling pathway modulators; in general, at least 4 weeks must have elapsed from any other anticancer therapy
* Able to undergo contrast enhanced magnetic resonance imaging (MRI) scans or CT scans
* Shown unequivocal evidence for contrast enhancing tumor progression by MRI or CT in comparison to a prior scan
* Age \> or = 18 years
* Karnofsky Performance Status \> or = 70
* Life expectancy of \> 8 weeks
* Normal organ and marrow function, adequate liver function, and adequate renal function before starting therapy
* Platelet count of at least 100,000/mm3 on at least 2 consecutive blood draws at least 1 week apart with results stable or trending upward
* Normal coagulation
* Cholesterol level \< or = 350 mg/dl and triglycerides level \< or = 400 mg/dl
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
* Women of childbearing potential must have a negative beta-human chorionic gonadotropin (B-hCG) pregnancy test documented within 7 days prior to treatment
* Women must agree not to breast feed
* Ability to understand and the willingness to sign a written informed consent document
* Ability to swallow tablets

Group A (medical) specific inclusion criteria:

* Fulfill all of the general inclusion criteria
* At least 3 months between any prior brain radiotherapy and initiation of study therapy
* MRI/CT must demonstrate measurable enhancing tumor of at least 1cm squared in cross-sectional area to allow assessment of radiographic response
* On stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI/CT
* The baseline brain MRI/CT must be performed less than 15 days prior to initiation of study treatment. Otherwise it must be repeated

Group B (surgical) specific inclusion criteria:

* Fulfill all of the general inclusion criteria
* Have cytoreductive surgery as part of their routine care for recurrent tumor
* Have cytoreductive surgery as part of their routine care for recurrent tumor
* A brain MRI/CT must be performed less than 15 days prior to initiation of study treatment. Otherwise it must be repeated

Exclusion Criteria:

* There is no limit on the number or type of prior chemotherapies except:

  1. convection enhanced delivery, catheter based intra-tumoral treatment, or carmustine (BCNU)/Gliadel® wafers
  2. stereotactic radiosurgery, or re-irradiation of any type
  3. agent designed to inhibit mTOR or PI3K/AKT
  4. direct Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitors
* Smoking or plan to smoke tobacco or marijuana during study therapy
* Plan to eat grapefruit or drink grapefruit juice during study therapy
* Receiving any other investigational agents concurrently with study treatment
* Taking hepatic Enzyme Inducing Anti-Epileptic Drug (EIAED)
* Taking medications that are inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) for at least two weeks prior to study treatment
* Uncontrolled intercurrent illness
* HIV-positive patients on combination antiretroviral therapy
* Other active concurrent malignancy
* History of gout which can be exacerbated by perifosine
* Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or perifosine
* Therapeutic anticoagulation
* History of hemorrhagic or ischemic stroke
* Prior intratumoral bleeding must be evaluated with a non-contrast head CT to exclude acute blood prior to start of treatment