Clinical Trial: Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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 def
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy [ Time Frame: Day 1 of tipifarnib therapy to week 8 ]
    The dose limiting toxicity (DLT) analysis population consists of phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD.
  • Progression-free Survival (PFS) [ Time Frame: Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks. ]
    PFS was defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.


Original Primary Outcome:

Current Secondary Outcome:

  • Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ]
    This study attempted to investigate in an exploratory manner the effect of treatment on changes in neuroimaging meaurements. Neuroimaging changes may have some association with outcome (response, survival, etc.). Perfusion values are obtained from magnetic resonance perfusion imaging and were measured at baseline, every 8 weeks for the first 48 weeks, and then every 12 weeks until treatment is discontinued.
  • Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation. [ Time Frame: Baseline and two weeks post completion of radiation ]
    This study attempted to investigate in an exploratory manner the effect of treatment on changes in neuroimaging meaurements. Neuroimaging changes may have some association with outcome (response, survival, etc.). Diffusion values are obtained from magnetic resonance diffusion imaging and were measured at baseline, every 8 weeks for the first 48 weeks, and then every 12 weeks until treatment is discontinued.
  • Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation [ Time Frame: Baseline and two weeks post completion of radiation ]
    This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response, survival, etc.). Volume FLAIR is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. Volume FLAIR was obtained at baseline and within two weeks after completion of radiation.
  • Mean Tumor to Gray Matter Ratio Measured at Baseline [ Time Frame: Baseline ]
    This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal gray matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to gray matter ratio value and the median of these values across patients is reported.
  • Mean Tumor to White Matter Ratio Measured at Baseline [ Time Frame: Baseline ]
    This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal white matter to provide ratios of tumor/white matter. Each patient has a mean tumor to white matter ratio value and the median of these values across patients is reported.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: March 8, 2004
Date Started: January 2004
Date Completion:
Last Updated: April 29, 2014
Last Verified: December 2012