Capecitabine and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Nonmetastatic Brain Stem Glioma or High-Grade Glioma
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|ClinicalTrials.gov Identifier: NCT00357253|
Recruitment Status : Completed
First Posted : July 27, 2006
Last Update Posted : January 10, 2013
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|
- 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)|
|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|
- 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.
- Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy [ Time Frame: First 11 weeks of therapy ]
- Dose-limiting toxicity [ Time Frame: First 11 weeks of therapy ]
- Pharmacokinetics of capecitabine RDT measured periodically during course 1 [ Time Frame: Day 1 and Day 14 of therapy ]
- 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.
- Survival [ Time Frame: From initiation of treatment until death or off study ]
- 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 ]
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 ClinicalTrials.gov 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|
|Study Chair:||Susan M. Blaney, MD||Texas Children's Cancer Center|