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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00357253
Recruitment Status : Completed
First Posted : July 27, 2006
Last Update Posted : January 10, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium

Brief 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.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: capecitabine Radiation: radiation therapy Phase 1

Detailed Description:



  • 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 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas
Study Start Date : January 2006
Actual Primary Completion Date : March 2010
Actual Study Completion Date : March 2010

Intervention Details:
  • 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.

Primary Outcome Measures :
  1. Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy [ Time Frame: First 11 weeks of therapy ]
  2. Dose-limiting toxicity [ Time Frame: First 11 weeks of therapy ]

Secondary Outcome Measures :
  1. Pharmacokinetics of capecitabine RDT measured periodically during course 1 [ Time Frame: Day 1 and Day 14 of therapy ]
  2. Tumor response [ Time Frame: From day 1 of treatment until off study ]
    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.

  3. Survival [ Time Frame: From initiation of treatment until death or off study ]
  4. 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 ]

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • One of the following newly diagnosed, nondisseminated brain tumors:

    • Intrinsic infiltrating brain stem glioma

      • Histopathologic diagnosis not required
    • Histopathologically confirmed high-grade glioma, meeting all of the following criteria:

      • Underwent prior definitive surgery ≤ 28 days ago with incompletely resected disease
      • Any of the following subtypes allowed:

        • Anaplastic astrocytoma
        • Glioblastoma multiforme
        • Other high-grade glioma
  • No anaplastic oligodendroglioma


  • Karnofsky performance scale (PS) 50-100% (if > 16 years of age) or Lansky PS 50-100% (if ≤ 16 years of age)
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³ (transfusion independent)
  • Hemoglobin ≥ 8 g/dL (transfusion independent)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age as follows:

    • No more than 0.8 mg/dL (for patients 5 years of age and under)
    • No more than 1 mg/dL (for patients 6-10 years of age)
    • No more than 1.2 mg/dL (for patients 11-15 years of age)
    • No more than 1.5 mg/dL (for patients over 15 years of age)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or other systemic disease
  • No known hypersensitivity to capecitabine or any of its components
  • No known dihydropyrimidine dehydrogenase (DPD) deficiency


  • See Disease Characteristics
  • Prior dexamethasone and/or surgery allowed
  • No prior chemotherapy, radiotherapy, immunotherapy, or bone marrow transplantation
  • No other concurrent anticancer or experimental drug therapies or agents
  • No concurrent warfarin or sorivudine or its chemically related analogues (e.g., brivudine)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00357253

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Study Chair: Susan M. Blaney, MD Texas Children's Cancer Center

Responsible Party: Pediatric Brain Tumor Consortium Identifier: NCT00357253     History of Changes
Other Study ID Numbers: CDR0000484429
U01CA081457 ( U.S. NIH Grant/Contract )
First Posted: July 27, 2006    Key Record Dates
Last Update Posted: January 10, 2013
Last Verified: January 2013

Keywords provided by Pediatric Brain Tumor Consortium:
untreated childhood brain stem glioma
childhood high-grade cerebral astrocytoma
untreated childhood cerebellar astrocytoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents