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

PURPOSE: This phase I/II trial is studying the side effects and best dose of tipifarnib to see how well it works when given together with radiation therapy in treating young patients with newly diagnosed brain stem glioma. (Phase I closed to accrual as of 1/3/06)

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of tipifarnib when administered with radiotherapy in patients with non-disseminated, diffuse, intrinsic brainstem gliomas.
• Determine the efficacy of this regimen in these patients.

Secondary

• Determine the toxic effects of this regimen in these patients.
• Determine the radiographic changes of brainstem gliomas using MRI, perfusion and diffusion imaging, and positron-emission tomography scans in patients treated with this regimen.

OUTLINE: This is a phase I (closed to accrual as of 1/3/06), multicenter, dose-escalation study of tipifarnib followed by a phase II safety and efficacy study.

• Phase I (closed to accrual as of 1/3/06): Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tipifarnib during radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose level preceding that at which 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/3/06) . Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 1 year.

PROJECTED ACCRUAL: A total of 3-46 patients (3-12 patients for phase I [closed to accrual as of 1/3/06] and a total of 40 patients for phase II [including 6 patients treated in the dose-finding portion of phase I (closed to accrual as of 1/3/06)]) will be accrued for this study within 2.3 years.

• Drug: tipifarnib
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed non-disseminated, intrinsic diffuse brainstem glioma

  • Newly diagnosed disease
  • No disseminated disease

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 50-100% (patients 17 to 21 years of age) OR
• Lansky 50-100% (patients 3 to 16 years of age)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3*
• Hemoglobin ≥ 8 g/dL* NOTE: *Transfusion independent

Hepatic

• ALT and AST < 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 ULN

Renal

• Creatinine < ULN OR
• Glomerular filtration rate > 70 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• No other significant medical illness that would preclude study participation
• No uncontrolled infection
• No disease that would obscure toxicity or dangerously alter drug metabolism
• No known allergy to topical or systemic azoles (e.g., fluconazole, ketoconazole, or itraconazole)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa
• No prior bone marrow transplantation

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No concurrent enzyme-inducing anticonvulsant drugs (EIACD)

  • Patients switched from EIACD to non-EIACD for at least 7 days before study participation allowed
• No other concurrent anticancer therapy
• No other concurrent experimental drugs