Phase 1 Intrathecal Topotecan for Neoplastic Meningitis (PBTC-019)
- 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.
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.
- To determine if intrathecal topotecan is beneficial to patients.
- To better understand how topotecan is handled by the body after intrathecal administration.
- To evaluate the cerebrospinal fluid for signs (markers) of tumor spread.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||A Phase I Pharmacokinetic Optimal Dosing Study of Intrathecal Topotecan for Children With Neoplastic Meningitis|
- To estimate the MTD of intrathecal topotecan administered daily for 5 consecutive days. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- To describe the toxicities and define the dose-limiting toxicity of intrathecally administered topotecan following intraventricular administration daily for 5 consecutive days. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
- To determine if the MTD of intrathecal topotecan is also a pharmacokinetic optimal dose as defined by topotecan lactone concentrations in the cerebral CSF. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
- To provide preliminary descriptions of the anti-tumor activity of intraventricular topotecan observed in the heterogeneous diseases that will be treated in this trial. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To investigate MMP, VEGF, and other potential biological markers in the CSF of patients with neoplastic meningitis prior to and throughout treatment with intrathecal topotecan. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To further describe the CSF pharmacokinetics of topotecan following intrathecal administration. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intrathecal therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2005|
|Study Completion Date:||December 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
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.
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.
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Susan Blaney, MD||Baylor College of Medicine|