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

Phase 1/Phase 2
3 Years
21 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

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



- 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)


- 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.

Inclusion Criteria


- Diagnosis of intrinsic pontine brain stem glioma within the past 30 days

- Histologic confirmation not required provided the tumor has a pontine epicenter
AND exhibits diffuse (rather than focal) involvement of ≥ 2/3 of the pons with
or without extension to the adjacent medulla or midbrain* NOTE: *Brain stem
tumors that do not meet these criteria must be histologically confirmed as grade
III or IV malignant glioma

- Measurable disease by radiographic imaging

- Post-operative MRI required within the past 30 days if patient had a biopsy or
surgical resection

- No disseminated disease

- No neurofibromatosis type 1



- 3 to 21 at diagnosis

Performance status

- Lansky 50-100% OR

- Karnofsky 50-100%

Life expectancy

- At least 8 weeks


- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 10.0 g/dL (transfusion allowed)


- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT < 2.5 times ULN


- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

- Creatinine based on age as follows:

- No greater than 0.8 mg/dL (for patients ≤ 5 years of age)

- No greater than 1.0 mg/dL (for patients 6 to 10 years of age)

- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)

- No greater than 1.5 mg/dL (for patients over 15 years of age)


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Not severely somnolent or comatose

- Central cortical neurotoxicity scale < grade 3


Biologic therapy

- No concurrent immunomodulating agents


- No other concurrent anticancer chemotherapy

Endocrine therapy

- Concurrent corticosteroids allowed for neurological deficits related to the tumor


- No prior radiotherapy


- See Disease Characteristics

- Prior biopsy or surgical resection for malignant brain stem glioma allowed


- No other prior therapy for malignant brain stem glioma

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Time to treatment failure (e.g., tumor progression, tumor recurrence, or death from any cause)

Safety Issue:


Principal Investigator

Patricia L. Robertson, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Michigan Cancer Center


United States: Federal Government

Study ID:




Start Date:

October 2005

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • untreated childhood brain stem glioma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



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