Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma

Brain Tumors Clinical Trial

Official title: A Phase I/II Study of Topotecan With G-CSF and Radiation Therapy in Children With Malignant Intrinsic Pontine Brainstem Gliomas of Childhood

Status Terminated

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Topotecan may make tumor cells more sensitive to radiation therapy . Giving topotecan and G-CSF together with radiation therapy may be an effective treatment for brain stem glioma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of topotecan when given together with G-CSF and radiation therapy and to see how well they work in treating young patients with newly diagnosed brain stem glioma.

Clinical Trial Description

OBJECTIVES:

Primary

• Determine the feasibility of escalating the dose of topotecan when administered with filgrastim (G-CSF) and radiotherapy, in terms of increasing the topotecan dose 25-50% above the maximum tolerated dose (MTD) determined in a prior phase I study, in young patients with newly diagnosed malignant intrinsic pontine brain stem glioma. (Phase I)

• Determine the dose-limiting toxic effects of topotecan in these patients. (Phase I)

• Determine the 1-year event-free survival and overall survival of patients treated with this regimen (at the MTD of topotecan determined in phase I). (Phase II)

• Determine the toxicity of this regimen in these patients. (Phase II)

Secondary

• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study of topotecan followed by a phase II study.

• Phase I: Patients receive topotecan IV over 30 minutes followed by radiotherapy once daily, 5 days a week for 6-7 weeks. During chemoradiotherapy, patients also receive filgrastim (G-CSF) IV or subcutaneously daily, if needed, until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 out of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive topotecan (at the MTD determined in phase I ), G-CSF, and radiotherapy as in phase I.

After completion of study treatment, patients are followed within 2 weeks, every 3 months for 1.5 years, every 6 months for 1.5 years, and then annually until disease relapse.

PROJECTED ACCRUAL: A total of 3-72 patients (3-12 for phase I and 60 for phase II) will be accrued for this study within approximately 3 years. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Nervous System Neoplasms

• NCT number: NCT00107471
• Study type: Interventional
• Source: Children's Oncology Group
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 2005