Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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.

Eligibility 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)

Trial Contact Information

Trial Lead Organizations/Sponsors

Pediatric Brain Tumor Consortium

Susan M. Blaney

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00357253
Information obtained from ClinicalTrials.gov on December 14, 2011

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