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

Inclusion Criteria

• Patients must have unstained slides or tissue blocks available from at least one prior surgery; frozen tissue is also requested if available
• Patients must have received prior radiotherapy and temozolomide; there is otherwise no limit on the number of prior recurrences/therapies
• At least 6 weeks (42 days) must have elapsed since completion of radiation therapy to initiation of study treatment
• At least 4 weeks (28 days) must have elapsed since most recent temozolomide and initiation of study treatment
• Patients must have recovered from the toxic effects of other prior direct inhibitors of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR): 4 weeks from prior therapy with agents such as bevacizumab (Avastin), aflibercept (VEGF-Trap), cediranib (AZD2171), or XL-184 (BMS 907351); any questions regarding the definition of a direct anti-VEGF/VEGFR therapy must be discussed with the principal investigator (PI) or co-PI; patients must have recovered from the toxic effects of other prior therapy including: 4 weeks (28 days) from any investigational agent, two weeks (14 days) from vincristine, 6 weeks (42 days) from nitrosoureas, 3 weeks (21 days) from procarbazine administration, and 1 week (7 days) for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count), and 4 weeks (28 days) from any other prior cytotoxic therapy; any questions related to the definition of non-cytotoxic agents should be directed to the co-PI
• Patients must have shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI)/computed tomography (CT) on the baseline MRI/CT in comparison to a prior scan OR have recently undergone resection for recurrent/progressive disease; the baseline brain MRI/CT must be performed 14 days or fewer prior to treatment; the same type of scan, i.e., MRI (or CT for patients who cannot undergo MRI) must be used throughout the period of protocol treatment for tumor measurement; criteria for progression on this study are not mandatory if the disease progression is obvious in the opinion of the investigator; any questions should be addressed to the PI
• Patients must be on a stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI/CT (and positron emission tomography [PET] scans for patients on the phase II study) except patients undergoing surgery on the surgical substudy of phase II; if the corticosteroid dose is increased between the date of imaging and registration a new baseline MR/CT is required
• Karnofsky performance status >= 60%
• Life expectancy of greater than 8 weeks
• White blood cell (WBC) >= 2,000/ul
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count of >= 100,000/mm^3
• Platelet count of at least 100, 000/mm^3 on at least 2 consecutive blood draws, at least 1 week apart, with results stable/trending upward; any question regarding the definition of stable/trending upward must be discussed with the PI
• Hemoglobin >= 10 gm/dl; eligibility level for hemoglobin may be reached by transfusion
• Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) < 2 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• Creatinine < 1.5 mg/dL
• Calcium levels at or above the lower limit of normal
• Phosphorus levels at or above the lower limit of normal
• Cholesterol level =< 350 mg/dl
• Triglycerides level =< 400 mg/dl
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin (B-HCG) pregnancy test documented within 7 days prior to treatment

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