• Progression-free survival at 1 year [ Designated as safety issue: No ]
  

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.