RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining tipifarnib with radiation therapy may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining tipifarnib with radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme.

OBJECTIVES:

• Determine the progression-free and overall survival of patients with newly diagnosed glioblastoma multiforme treated with tipifarnib and radiotherapy.
• Determine the response rate of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive oral tipifarnib twice daily for 3 weeks. Treatment repeats every 4 weeks for up to 3 courses.
• Radiotherapy: Within 14 days after the completion of induction therapy, patients undergo radiotherapy daily, 5 days a week, for 6 weeks.
• Maintenance therapy: Two weeks after the completion of radiotherapy, patients receive additional tipifarnib as in induction therapy.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A minimum of 54 patients will be accrued for this study within 11-14 months.

• Drug: tipifarnib
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade IV astrocytoma

  • Glioblastoma multiforme
• Measurable and contrast-enhancing tumor on the postoperative MRI/CT scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• AST/ALT no greater than 4 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Mini-mental state exam score at least 15
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No serious concurrent infection that would preclude study therapy
• No other medical illness that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy for brain tumor

• No prior biologic therapy for brain tumor, including any of the following:

  • Immunotoxins
  • Immunoconjugates
  • Antisense therapy
  • Peptide receptor antagonists
  • Interferons
  • Interleukins
  • Tumor-infiltrating lymphocytes
  • Lymphokine-activated killer cell therapy
  • Gene therapy

Chemotherapy

• No prior chemotherapy for brain tumor
• No prior polifeprosan 20 with carmustine implant (Gliadel wafer)

Endocrine therapy

• No prior hormonal therapy (except glucocorticoids) for brain tumor
• Must be maintained on a stable corticosteroid regimen prior to study entry

Radiotherapy

• No prior radiotherapy for brain tumor

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• At least 10 days since prior hepatic metabolic enzyme-inducing anticonvulsant drugs, including the following:

  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Primidone
  • Oxcarbazepine
• No other concurrent investigational agents