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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00357253
First received: July 26, 2006
Last updated: January 8, 2013
Last verified: January 2013

July 26, 2006
January 8, 2013
January 2006
March 2010   (final data collection date for primary outcome measure)
  • Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy [ Time Frame: First 11 weeks of therapy ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [ Time Frame: First 11 weeks of therapy ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00357253 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics of capecitabine RDT measured periodically during course 1 [ Time Frame: Day 1 and Day 14 of therapy ] [ Designated as safety issue: No ]
  • Tumor response [ Time Frame: From day 1 of treatment until off study ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
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Capecitabine and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Nonmetastatic Brain Stem Glioma or High-Grade Glioma
A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • 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.
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
March 2010
March 2010   (final data collection date for primary outcome measure)

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)
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00357253
CDR0000484429, U01CA081457, PBTC-021
Yes
Pediatric Brain Tumor Consortium
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Study Chair: Susan M. Blaney, MD Texas Children's Cancer Center
Pediatric Brain Tumor Consortium
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP