NCT00112619

Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors

A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Pediatric Brain Tumor Consortium · Network
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of topotecan when given by intraventricular infusion in treating young patients with neoplastic meningitis due to leukemia, lymphoma, or solid tumors.

Detailed description

OBJECTIVES: Primary * 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 these patients. Secondary * 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 week 5. 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 months.

Conditions

• Brain and Central Nervous System Tumors
• Carcinoma of Unknown Primary
• Leukemia
• Lymphoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	topotecan hydrochloride	Participants receive intraventricular topotecan, .2 mg, administered via an indwelling ventricular reservoir daily for 5 consecutive days during weeks 1 and 3 of the first four weeks of therapy (induction), during weeks 5 and 8 of the next 6 weeks of therapy (consolidation), and during weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51 (maintenance therapy).

Timeline

• Start date: 2005-08-01
• Primary completion: 2010-08-01
• First posted: 2005-06-03
• Last updated: 2011-06-30

Locations

11 sites across 1 country: United States