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

DISEASE CHARACTERISTICS:

* Histologically confirmed diagnosis of 1 of the following:

  * Glioblastoma multiforme (grade 4 astrocytoma)
  * Other grade 4 astrocytoma variants (e.g., giant cell)

    * No grade 4 oligodendrogliomas or oligoastrocytomas
  * Gliosarcoma
* Newly diagnosed disease
* Measurable disease ≥ 1 cm³ (phase I patients only)
* Some patients may be registered on protocol NCCTG-947252
* No oligodendrogliomas or oligoastrocytomas

PATIENT CHARACTERISTICS:

Inclusion criteria:

* ECOG performance status 0-2
* ANC ≥ 1,500/μL
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/μL
* Total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
* Serum total cholesterol \< 350 mg/dL
* Serum total triglycerides \< 400 mg/dL
* AST ≤ 2.5 x ULN
* Creatinine ≤ 1.5 x ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 60 days after completion of study therapy
* Must be willing to undergo 2 mandatory research PET or PET/CT scans (all MCR and MCJ patients in phase I and MCR only patients in phase II)
* Must be willing to abstain from eating or drinking grapefruit or grapefruit juice during study treatment
* Must be willing to follow a diet low in fat and cholesterol while taking everolimus
* Must be willing to have imaging scans submitted for central review
* Ability to understand and willingness to sign a written informed consent

Exclusion criteria:

* Other active cancers requiring therapy to control disease or prior cancer diagnoses which pose a greater than 30% risk of death within the next 2 years
* Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active uncontrolled peptic ulcer disease
* Uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing, uncontrolled, or active (acute or chronic) infection or disorder
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
  * Severely impaired lung function
  * Uncontrolled diabetes (fasting serum glucose \> 2 x ULN) OR diabetes that would interfere with the performance of the FDG-PET/CT or FDG-PET scans
  * Liver disease (e.g., cirrhosis, chronic active hepatitis, chronic persistent hepatitis, or history of hepatitis B)
* Known HIV positivity
* Positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests
* Any history of allergy or intolerance to dacarbazine (DTIC)
* Significant traumatic injury within the past 21 days
* Severe allergy to sulfa medications
* Inability to tolerate levofloxacin with dapsone or pentamidine (inhaled or IV)

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

* At least 1 week, but no more than 6 weeks since prior surgical resection or biopsy
* Must comply with antibiotic prophylaxis with either trimethoprim/sulfamethoxazole (daily or 3 times per week), oral dapsone (daily) combined with daily levofloxacin, or monthly pentamidine (inhaled or IV) combined with daily levofloxacin

Exclusion criteria:

* Prior chemotherapy for any brain tumor
* Prior temozolomide or mTOR inhibitor therapies
* Any prior cranial radiotherapy
* Planned immunization with attenuated live vaccines ≤ 7 days prior to and during study period
* At least 21 days since prior major surgery (excluding neurosurgical biopsy, resection of brain tumor, or treatment of immediate post-neurosurgical complication \[e.g., intracranial hematoma\])
* Concurrent or prior treatment for this cancer with any other investigational agents
* Concurrent enzyme-inducing anticonvulsants (EIACs) or other strong inducers of CYP3A4 (i.e., carbamazepine, phenytoin, phenobarbital/primidone, rifabutin, rifampin, or St. John's wort)
* Concurrent therapeutic doses of warfarin

  * Low molecular weight heparin is allowed
* Concurrent systematic leukocyte growth factors (e.g., G-CSF or GM-CSF), except for the treatment of severe neutropenia
* Concurrent drugs or substances known to inhibit or induce CYP3A
* Other concurrent chronic treatment with immunosuppressive agents except dexamethasone
* Other concurrent anticancer agents
* Concurrent live vaccines