Phase I/II Trial Of R115777 And XRT In Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas
- 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.
- 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.
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 Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
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.
Day 1 of tipifarnib therapy to week 8
Daphne A. Haas-Kogan, MD
University of California, San Francisco
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|