NCT00357253

Capecitabine and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Nonmetastatic Brain Stem Glioma or High-Grade Glioma

A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Pediatric Brain Tumor Consortium · Network
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Capecitabine may make tumor cells more sensitive to radiation therapy. Giving capecitabine together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with radiation therapy in treating young patients with newly diagnosed, nonmetastatic brain stem glioma or high-grade glioma.

Detailed description

OBJECTIVES: Primary * 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. Secondary * 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 tablets (RDT). 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 courses. 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 unacceptable toxicity. 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.

Conditions

• Brain and Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	capecitabine	This is a dose escalation study. 375, 500, 650, or 850 mg/m2 capecitabine RDT is given orally daily in two divided doses approximately 12 hours apart beginning at the start of radiation therapy and continuing for 9 weeks. After a two week break, patients receive twice daily oral capecitabine, either 900 mg/m2 or 1250 mg/m2, approximately 12 hours apart for 14 days followed by a 7-day rest period for a total of 3 courses.
RADIATION	radiation therapy	Participants receive local radiation once daily, 5 days/week for 9 weeks for a total dose of 5580 cGy.

Timeline

• Start date: 2006-01-01
• Primary completion: 2010-03-01
• Completion: 2010-03-01
• First posted: 2006-07-27
• Last updated: 2013-01-10

Locations

12 sites across 1 country: United States