NCT00674674

Phase 1 Intrathecal Topotecan for Neoplastic Meningitis

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

1. To find the optimal dose of topotecan that can safely be given directly into the spinal fluid (called intrathecal administration) of children whose cancer has spread to the lining of the brain and/or spinal cord. 2. To find out what effects (good and bad) topotecan has when given directly into the cerebrospinal fluid in children with neoplastic meningitis (cancer that has spread to the lining of the brain and spinal cord). * Cerebrospinal fluid is the fluid that circulates around the brain and spinal cord. 3. To determine if intrathecal topotecan is beneficial to patients. 4. To better understand how topotecan is handled by the body after intrathecal administration. 5. To evaluate the cerebrospinal fluid for signs (markers) of tumor spread.

Detailed description

This is a multi-center, non-randomized pharmacokinetically-guided optimal dosing study of intraventricular topotecan in children with neoplastic meningitis. Topotecan will be administered daily for five consecutive days utilizing the schema shown in the Schema below. Concomitant chemotherapy to control systemic disease or bulk CNS disease is allowable provided that the systemic chemotherapy is not an investigational agent or one of the following: high-dose methotrexate (\> 1g/m2), high-dose cytarabine (\> 1g/m2), 5-fluorouracil, capecitabine, thiotepa, a nitrosourea, or topotecan. The starting dose for this trial was derived from pharmacokinetic simulations that utilized data from a prior phase I study of intrathecal topotecan. The simulations were performed to estimate the length of time that ventricular CSF concentrations of topotecan lactone would remain above an optimal "target level" of 1 ng/mL. One of the primary objectives of this study is to estimate the dose of intrathecal topotecan that will result in CSF lactone concentrations exceeding 1 ng/mL for at least eight hours after an intrathecal injection. Dose escalations for patient cohorts will be conducted following the traditional phase 1 design in order to determine the maximum tolerated dose (MTD). The MTD will be called pharmacokinetically optimal if that dose achieves the targeted PK parameter in at least 23 of 25 patients treated at that dose level.

Conditions

• Neoplastic Meningitis

Interventions

Type	Name	Description
DRUG	Topotecan	Induction (4 weeks): Patients will receive IT topotecan for 5 consecutive days during weeks 1 and 3. The Induction period is the first 4 weeks of therapy.
DRUG	Topotecan	Consolidation (6 weeks): Patients will receive IT topotecan for 5 consecutive days during weeks 1 and 4. The Consolidation period is 6 weeks in duration. Consolidation begins immediately after completion of the 4th week of Induction.
DRUG	Topotecan	Maintenance (4 weeks for 11 courses): Patients will receive IT topotecan for 5 consecutive days during week 1. Each course of Maintenance is 4 weeks in duration. Maintenance begins immediately after completion of the 6th week of Consolidation.

Timeline

• Start date: 2005-10-01
• Primary completion: 2010-08-01
• Completion: 2010-12-01
• First posted: 2008-05-08
• Last updated: 2012-05-15

Locations

1 site across 1 country: United States