Trial Information

Phase I/II Trial Of R115777 And XRT In Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas

OBJECTIVES:

Primary

- Determine the maximum tolerated dose (MTD) 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 magnetic resonance
imaging (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 1/19/06), multicenter, dose-escalation
study of tipifarnib followed by a phase II safety and efficacy study.

- Phase I (closed to accrual as of 1/19/06): 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 (total of 26 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 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 1/19/06) . Treatment continues for up to 24 months (26
courses) in the absence of disease progression or unacceptable toxicity.

FOLLOW-UP:

Phase I: Participants contributing only to the phase I part are followed for 90 days after
completion of therapy. Adverse events that have not resolved within 90 days after stopping
treatment will be followed until resolution.

Phase II: Participants in the phase I part treated at the MTD or participants in the phase
II part are followed until the earliest of death or three years after starting treatment.

PROJECTED ACCRUAL: A total of 3-55 patients (3-18 patients for phase I [closed to accrual as
of 1/19/06] 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 1/19/06)]) will be accrued for this
study within 2.3 years.