A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis
- Determine the maximum tolerated dose (MTD) of intraventricular topotecan in young
patients with neoplastic meningitis secondary to leukemia, lymphoma, or solid tumors.
- Determine the toxic effects and dose-limiting toxicity of this drug in these patients.
- Determine whether the MTD of this drug is also the pharmacokinetic optimal dose,
defined by the topotecan lactone concentration in the cerebral spinal fluid (CSF), in
- Determine, preliminarily, the antitumor activity of this drug in these patients.
- Determine the pharmacokinetics of this drug in the CSF of these patients.
- Correlate observed effects of post-treatment central review imaging (if feasible) with
response to this drug in these patients.
OUTLINE: This is a non-randomized, dose-escalation, multicenter study.
- Induction therapy (weeks 1-4): Patients receive topotecan intraventricularly* over 5
minutes on days 1-5 in weeks 1 and 3. Patients then proceed to consolidation therapy in
NOTE: *Patients who are willing, receive 1 intralumbar (instead of intraventricular) dose of
topotecan on day 1 of week 3 only.
- Consolidation therapy (weeks 5-10): Patients receive topotecan intraventricularly on
days 1-5 in weeks 5 and 8. Patients then proceed to maintenance therapy in week 11.
- Maintenance therapy (weeks 11-54): Patients receive topotecan intraventricularly on
days 1-5 in weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51.
Cohorts of 3-6 patients receive escalating doses of intraventricular topotecan 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.
Once the MTD is determined, the cohort is expanded to 25 patients and the MTD is declared
the pharmacokinetic optimal dose provided 23 of 25 patients treated at the MTD achieve the
target pharmacokinetic parameter.
PROJECTED ACCRUAL: A total of 28-49 patients will be accrued for this study within 9-24
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Estimate the maximum tolerated dose of intraventricular topotecan on this schedule
First 14 days of therapy
Susan M. Blaney, MD
Baylor College of Medicine
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|
|Dan L. Duncan Cancer Center at Baylor College of Medicine||Houston, Texas 77030|