Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma

Untreated Childhood Brain Stem Glioma Clinical Trial

Official title: Phase I/II Trial of R115777 and XRT in Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas

Status Completed

Clinical Trial Summary

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. 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 1/19/06)

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of R115777 administered concurrently with radiation therapy to pediatric patients with non-disseminated, diffuse, intrinsic brainstem gliomas who are not receiving enzyme-inducing anti-convulsant drugs (EIACD).

II. To assess the efficacy of R115777 treatment in combination with radiation therapy for patients with non-disseminated, diffuse, intrinsic pontine gliomas as measured by progression-free survival and survival distributions.

SECONDARY OBJECTIVES:

I. To characterize toxicities associated with R115777 treatment in combination with and post radiation therapy.

II. To characterize radiographic changes in brainstem gliomas treated with radiation and R115777 using MRI, perfusion and diffusion imaging and PET scans.

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: 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. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioma
• Untreated Childhood Brain Stem Glioma

• NCT number: NCT00079339
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2004
• Completion date: November 2009