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

Phase 1
3 Years
21 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

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
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

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.

Inclusion Criteria


- 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

- Underwent prior definitive surgery ≤ 28 days ago with incompletely resected

- 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.,

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy

Outcome Time Frame:

First 11 weeks of therapy

Safety Issue:


Principal Investigator

Susan M. Blaney, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Texas Children's Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2006

Completion Date:

March 2010

Related Keywords:

  • Brain and Central Nervous System Tumors
  • untreated childhood brain stem glioma
  • childhood high-grade cerebral astrocytoma
  • untreated childhood cerebellar astrocytoma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



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