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

• Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy [ Time Frame: First 11 weeks of therapy ] [ Designated as safety issue: Yes ]
  
• Dose-limiting toxicity [ Time Frame: First 11 weeks of therapy ] [ Designated as safety issue: Yes ]
  

• Pharmacokinetics of capecitabine RDT measured periodically during course 1 [ Time Frame: Day 1 and Day 14 of therapy ] [ Designated as safety issue: No ]
  
• Tumor response [ Time Frame: From day 1 of treatment until off study ] [ Designated as safety issue: No ]
  Brain imaging to assess tumor response to the treatment is performed at baseline, week 11, end of course 6, and then every 3 months for two years.
  
  
• Survival [ Time Frame: From initiation of treatment until death or off study ] [ Designated as safety issue: No ]
  
• Radiographic changes in gliomas as measured by MRI, magnetic resonance spectroscopy (MRS), perfusion and diffusion MRI [ Time Frame: Baseline, week 11, then every 3 months for 2 years or until off study ] [ Designated as safety issue: No ]
  

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.
Other Name: Xeloda
Radiation: radiation therapy
Participants receive local radiation once daily, 5 days/week for 9 weeks for a total dose of 5580 cGy.

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.