A Study of Temsirolimus and Bevacizumab in Recurrent Glioblastoma Multiforme

Inclusion Criteria: * Written informed consent * Histological verification of primary GBM and failure after radiotherapy and temozolomide (TMZ) * Previously treated with VEGF-directed therapy with bevacizumab * Previously received radiotherapy and temozolomide * More than 4 weeks since any of the following prior treatments: chemotherapy (6 weeks for nitrosoureas or mitomycin C) * Radiotherapy to nontarget lesions or lesions that are not to be biopsied VEGF-directed therapy (including bevacizumab) * Investigational agents * More than 6 months since prior major surgery or open biopsy and recovered (only 6 weeks required if operation is for recurrent GBM) * No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of the following: * Temsirolimus * Bevacizumab * CYP450 isoenzymes * ECOG performance status 0-1 * WBC ≥ 3,000 mm³ * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin and phosphate normal * AST and ALT ≤ 2.5 times upper limit of normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * Urine protein: creatinine ratio \< 1.0 OR 24-hour urine protein \< 1,000 mg * Fasting cholesterol \< 350 mg/dL (cholesterol medications are allowed) * Fasting triglycerides \< 400 mg/dL * PT INR ≤ 1.5 * Hematocrit \< 41% (for males) or \< 38% (for females) * Fertile females must use an approved contraceptive (p-pills, IUD, depot injection of gestagen, subdermal implantation, hormonal vaginal ring or transdermal depot plaster), throughout the study and 3 months after discontinuation of study drugs. Fertile men must use dobbelt barrier method (preservative with sperm inhibiting creme) or female partner uses the above mentioned contraceptive. * Fertile males must use preservatives. Exclusion Criteria: * Clinically significant cardiovascular disease, including the following: * Cerebrovascular accident within the past 6 months * Transient ischemic attack within the past 6 months * Myocardial ischemia within the past 6 months * Myocardial infarction within the past 6 months * Other thromboembolic event within the past 6 months * Unstable angina within the past 6 months * Uncontrolled hypertension (i.e., hypertension despite maximal therapy) * New York Heart Association class II-IV heart disease * Congestive heart failure * Serious cardiac arrhythmia requiring medication * Clinically significant peripheral vascular disease * Uncontrolled intercurrent illness * Ongoing or active infection * One of the following within the past 6 months * Abdominal fistula * Gastrointestinal perforation * Intra-abdominal abscess * Serious or nonhealing wound, ulcer, or bone fracture * Psychiatric illness or social situations that would preclude study compliance * Uncontrolled diabetes * Hemoglobin A1c \> 7% * Concurrent non-study related surgical procedures * Concurrent treatment with CYP3A4 inducers or inhibitors * Other concurrent anticancer agents or therapies * Significant traumatic injury within the past 28 days * History of allergic reactions to compounds of similar chemical or biological composition to temsirolimus or bevacizumab * Hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (e.g., infliximab) * Pregnancy or nursing * Patients previously intolerant to bevacizumab * Anticoagulant therapy