Capecitabine and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Nonmetastatic Brain Stem Glioma or High-Grade Glioma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): capecitabine; radiation therapy
Intervention type(s): Drug; Radiation
Intervention description(s): 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.; Participants receive local radiation once daily, 5 days/week for 9 weeks for a total dose of 5580 cGy.
Other intervention name(s): Xeloda
Intervention MeSH terms: Capecitabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated childhood brain stem glioma; childhood high-grade cerebral astrocytoma; untreated childhood cerebellar astrocytoma