Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (RTOG 0913)

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme (GBM) (WHO grade IV) by central pathology review

  • Gliosarcoma allowed
  • Tumor must have a supratentorial component

• Diagnosis must have been made by surgical excision, either partial or complete excision, within the past 5 weeks

  • Stereotactic biopsy or Cavitron ultrasonic aspirator-derived tissue are not allowed

• Tumor tissue available for correlative studies (phase II only)

  • Patients must have ≥ 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
• No recurrent or multifocal malignant glioma
• No metastases detected below the tentorium or beyond the cranial vault

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• ANC ≥ 1,800/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
• PT/INR ≤ 1.5
• BUN ≤ 30 mg/dL
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times normal
• ALT and AST ≤ 2.5 times normal
• Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 times ULN (if one or both of these thresholds are exceeded, patients are eligible only after initiation of appropriate lipid-lowering medication)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other invasive malignancy within the past 3 years except for nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

• No severe, active co-morbidity, defined as follows:

  • NYHA class III-IV symptomatic congestive heart failure
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the past 6 months, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
  • Severely impaired lung function, defined as spirometry and DLCO that is 50% of the normal predicted value and/or oxygen saturation that is ≤ 88% at rest on room air
  • Uncontrolled diabetes, defined as fasting serum glucose > 1.5 times ULN
  • Active (acute or chronic) or uncontrolled severe infections requiring IV antibiotics
  • Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
  • AIDS based upon current Centers for Disease Control and Prevention definition or known HIV seropositivity (HIV testing is not required for study entry)
  • Active connective tissue disorders such as lupus erythematosus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity
  • Other major medical illness or psychiatric impairment that, in the investigator's opinion, will prevent administration or completion of study treatment
• No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• No history of deep vein thrombosis or pulmonary embolism
• No prior allergic reaction to temozolomide
• No known hypersensitivity to mTOR inhibitors (e.g., sirolimus, temsirolimus, everolimus) or to their excipients

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from the effects of surgery, postoperative infection, and other complications
• No prior temozolomide
• No prior mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus)
• No prior Gliadel wafers or any other intratumoral or intracavitary treatment
• No prior radiotherapy to the head or neck (except for T1 glottic cancer) resulting in overlap of radiotherapy fields

• No prior chemotherapy or radiosensitizers for cancer of the head and neck region

  • Prior chemotherapy for a different cancer is allowed
• No prior radiotherapy or chemotherapy for GBM
• No prior or concurrent treatment on any other therapeutic clinical study
• At least 14 days since prior and no concurrent enzyme-inducing anti-epileptic drugs
• Concurrent anticoagulation allowed provided target INR ≤ 1.5 AND patient is on a stable dose of warfarin or low molecular weight heparin for > 2 weeks