A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas
- Estimate the maximum tolerated dose of capecitabine rapidly disintegrating tablets
(RDT) administered concurrently with radiotherapy in young patients with newly
diagnosed, nondisseminated intrinsic brain stem glioma or high-grade glioma.
- Describe the dose-limiting toxicity in patients treated with this regimen.
- Describe the safety profile of this regimen.
- Characterize the pharmacokinetics of capecitabine RDT in these patients.
- Explore the exposure-response relationship for measures of safety and effectiveness
using pharmacokinetic and pharmacodynamic models.
- Describe the antitumor activity of this regimen observed in these patients.
- Estimate distributions of progression-free survival and survival in patients treated
with this regimen.
- Characterize radiographic changes in tumor, using MRI, perfusion and diffusion MRI, and
positron emission tomography (PET) scans, in patients treated with this regimen.
OUTLINE: This a multicenter, dose-escalation study of capecitabine rapidly disintegrating
Patients undergo radiotherapy once daily, 5 days a week, for approximately 6 weeks.
Beginning within 24 hours of starting radiotherapy, patients also receive oral capecitabine
RDT twice daily on days 1-21. Treatment with capecitabine RDT repeats every 21 days for 3
Cohorts of 3-6 patients receive escalating doses of capecitabine RDT until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
Beginning in week 12, patients receive capecitabine RDT at a fixed dose twice daily on days
1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or
Patients undergo blood collection periodically during course 1 for pharmacokinetic
correlative studies. Patients also undergo MRI, and rapid perfusion/diffusion MRI at
baseline and periodically during study for radiographic correlative studies.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy
First 11 weeks of therapy
Susan M. Blaney, MD
Texas Children's Cancer Center
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|
|Dan L. Duncan Cancer Center at Baylor College of Medicine||Houston, Texas 77030|