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

Phase 1
Terminated
Conditions
Central Nervous System Tumors
Brain Tumors
Interventions
Biological: filgrastim
Radiation: radiation therapy
Registration Number
NCT00107471
Lead Sponsor
Children's Oncology Group
Brief 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.

Detailed 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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
7
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Dose Level I (0.5 mg/m^2)filgrastimRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n)
Dose Level I (0.5 mg/m^2)radiation therapyRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n)
Dose Level 2 (0.6 mg/m^2)filgrastimRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n.)
Dose Level I (0.5 mg/m^2)topotecan hydrochlorideRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n)
Dose Level 2 (0.6 mg/m^2)topotecan hydrochlorideRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n.)
Dose Level 2 (0.6 mg/m^2)radiation therapyRadiation Therapy + Topotecan hydrochloride daily before each dose of irradiation (radiation therapy) + filgrastim (G-CSF) (p.r.n.)
Primary Outcome Measures
NameTimeMethod
Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause)From date of enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death or until last contact if none of these events occur, assessed up to 3 years
Secondary Outcome Measures
NameTimeMethod
Time to deathFrom the time of study entry to the first occurrence of death by any cause

Trial Locations

Locations (80)

Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham

🇺🇸

Birmingham, Alabama, United States

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Southern California Permanente Medical Group

🇺🇸

Downey, California, United States

Children's Hospital Central California

🇺🇸

Madera, California, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

Sutter Cancer Center

🇺🇸

Sacramento, California, United States

Stanford Comprehensive Cancer Center - Stanford

🇺🇸

Stanford, California, United States

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

🇺🇸

Farmington, Connecticut, United States

Lee Cancer Care of Lee Memorial Health System

🇺🇸

Fort Myers, Florida, United States

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Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
🇺🇸Birmingham, Alabama, United States
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