Phase I/II Trial of Concurrent RAD001 (Everolimus) With Temozolomide/Radiation Followed by Adjuvant RAD001/Temozolomide in Newly Diagnosed Glioblastoma

Inclusion Criteria

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