Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Inclusion criteria: 1. Histologically proven diagnosis of glioblastoma (WHO grade IV) confirmed by central pathology review prior to Step 2 registration. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis. 2. Tumor tissue available for correlative studies (Required only in phase II portion, as described below). * Patients must have at least 1 block of tissue; if a block cannot be submitted, two tissue specimens punched with a skin punch (2 mm diameter) from the tissue block containing the tumor may be submitted. * Diagnosis must be made by surgical excision, either partial or complete. Stereotactic biopsy or Cavitron ultrasonic aspirator (CUSA)-derived tissue is not allowed for patients on Phase II, as it will not provide sufficient tissue for the required MGMT and pAKT/pMTOR analyses. 3. The tumor must have a supratentorial component 4. Patients must have recovered from the effects of surgery, postoperative infection, and other complications. 5. A diagnostic contrast-enhanced MRI or CT scan (if MRI is not available due to non-compatible devices) of the brain must be performed preoperatively and postoperatively. The postoperative scan must be done within 28 days prior to step 2 registration, ,preferably within 96 hours of surgery. Preoperative and postoperative scans must be the same type. • Patients unable to undergo MRI imaging because of non-compatible devices can be enrolled, provided pre- and post-operative contrast enhanced CT scans are obtained and are of sufficient quality. 6. History/physical examination within 14 days prior to step 2 registration 7. Neurologic examination within 14 days prior to step 2 registration 8. Documentation of steroid doses within 14 days prior to step 2 registration 9. Karnofsky performance status ≥ 70 10. Age ≥ 18 years 11. Complete blood count (CBC)/differential obtained within 14 days prior to step 2 registration, with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3; * Platelets ≥ 100,000 cells/mm3; * Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.) 12. Prothrombin time/international normalized ratio (PT INR) ≤ 1.5 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration. Patients on full-dose anticoagulants (eg, warfarin or low molecular weight heparin) must meet both of the following criteria: * No active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices) * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin 13. Adequate renal function, as defined below: * Blood urea nitrogen (BUN) ≤ 30 mg/dl within 14 days prior to step 2 registration * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) within 14 days prior to step 2 registration 14. Adequate hepatic function, as defined below: * Bilirubin ≤ 1.5 x normal range within 14 days prior to step 2 registration * Alanine aminotransferase (ALT) ≤ 2.5 x normal range within 14 days prior to step 2 registration * Aspartate aminotransferase (AST) ≤ 2.5 x normal range within 14 days prior to step 2 registration 15. Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN (upper limit of normal). Note: If one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. 16. For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration 17. Women of childbearing potential and male participants must practice adequate contraception 18. Patient must provide study-specific informed consent prior to registration Exclusion criteria: 1. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) 2. Recurrent or multifocal malignant glioma 3. Metastases detected below the tentorium or beyond the cranial vault 4. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment 5. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation therapy fields 6. Prior chemotherapy or radiosensitizers for cancer of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or RAD001. 7. Prior radiation therapy or chemotherapy for glioblastoma 8. Severe, active co-morbidity, defined as follows: * Symptomatic congestive heart failure of New York heart Association Class III or IV * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the last 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease * Severely impaired lung function as defined as spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air * Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN * Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition or known HIV seropositivity; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. * Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity * Other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy