A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas
3 Years
21 Years
Both
Brain and Central Nervous System Tumors
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
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- 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)
Type of Study:
Interventional
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:
Yes
Principal Investigator
Susan M. Blaney, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Texas Children's Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000484429
NCT ID:
NCT00357253
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
Name | Location |
|---|---|
| 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 |
