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