Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma
Condition: Untreated Childhood Brain Stem Glioma
MeSH terms: Glioma
Study type: Interventional
Phase: Phase 1/Phase 2

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)
    

Detailed 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.
    

Intervention name(s): radiation therapy; tipifarnib
Intervention type(s): Radiation; Drug
Intervention description(s): Undergo radiotherapy; Given orally
Other intervention name(s): irradiation; radiotherapy; therapy, radiation; R115777; Zarnestra
Intervention MeSH terms: Tipifarnib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment