A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies
I. Determine the therapeutic activity of intrathecal topotecan, in terms of response rate
and time to central nervous system (CNS) progression, in pediatric patients with recurrent
or refractory neoplastic meningitis.
II. Determine the safety and toxicity of this regimen in these patients. III. Evaluate the
concentration of matrix metalloproteinases (MMPs) in the cerebrospinal fluid (CSF) of these
OUTLINE: Patients are stratified according to disease type (acute lymphoblastic leukemia vs.
other leukemia/lymphoma vs medulloblastoma vs other solid tumors). (Recurrent CNS acute
lymphoblastic leukemia stratum only open to accrual as of 11/30/04)
INDUCTION: Patients receive topotecan hydrochloride intrathecally (IT) over 5 minutes twice
weekly for 6 weeks.
CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan
hydrochloride IT over 5 minutes weekly for 4 weeks in the absence of disease progression or
MAINTENANCE: Beginning 2 weeks after completion of consolidation, patients receive topotecan
hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1.
After completion of study treatment, patients are followed up monthly for 3 months, every 3
months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 14-77 patients will be accrued for this study.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
For the leukemia and lymphoma patients, an objective response rate, defined to be the proportion of Complete Responses of less than 0.10
Up to 54 months
Children's Oncology Group
United States: Food and Drug Administration
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