RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining tipifarnib, temozolomide, and radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

OBJECTIVES:

• Determine the maximum tolerated dose of tipifarnib when given in combination with temozolomide and radiotherapy followed by adjuvant tipifarnib and temzolomide in patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
• Determine the safety of this regimen in these patients.
• Determine any evidence of antitumor activity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes [closed to accrual as of 3/15/05] vs no).

• Combination therapy: Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within 5-9 days after beginning tipifarnib, patients receive oral temozolomide once daily for 6 weeks and concurrently undergo partial brain radiotherapy daily 5 days a week for 6 weeks. After completion of radiotherapy, patients proceed to adjuvant therapy.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.

• Adjuvant therapy: Patients continue to receive tipifarnib as above. With the initiation of the next planned course of tipifarnib, patients receive oral temozolomide on days 1-5. Treatments repeats every 28 days for 12 courses OR 1 year (whichever is longer) in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients with progressive disease are followed at 10 weeks and then every 4 months. Patients who complete therapy are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter until disease progression.

PROJECTED ACCRUAL: Approximately 9-19 patients will be accrued for this study within 6 months.

• Drug: temozolomide
• Drug: tipifarnib
• Procedure: adjuvant therapy
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma

  • Established by biopsy or resection within the past 4 weeks

• Planned external beam partial brain radiotherapy to begin within 5-9 days after beginning study drug and within 35 days of prior diagnostic biopsy or resection

  • No concurrent stereotactic radiosurgery or brachytherapy
  • Planned total dose to tumor of 60.0 Gy in daily fractions of 2.0 Gy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL (transfusions allowed)

Hepatic

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT less than 2 times ULN

Renal

• Creatinine less than 1.5 mg/dL

Other

• No active infection
• No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
• No other significant uncontrolled medical illness that would preclude study participation
• No disease that would obscure toxicity or dangerously alter drug metabolism
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent sargramostim (GM-CSF)
• No concurrent filgrastim (G-CSF) during first course of therapy

Chemotherapy

• No prior polifeprosan 20 with carmustine implant
• No concurrent chemotherapy

Endocrine therapy

• Prior corticosteroids allowed
• Concurrent corticosteroids allowed
• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy to the brain

Surgery

• See Disease Characteristics

Other

• Prior enzyme-inducing antiepileptic drugs (EIAEDs), analgesics, or other drugs to treat symptoms or prevent complications are allowed
• No prior cytotoxic, noncytotoxic, or experimental drug therapy for this disease
• No other concurrent investigational drugs
• No concurrent participation in another clinical study
• No other concurrent drug therapy for this disease
• No concurrent chronic warfarin except for deep venous thrombosis or pulmonary embolism
• Concurrent EIAEDs, analgesics, or other drugs to treat symptoms or prevent complications are allowed