Phase 1 Intrathecal Topotecan for Neoplastic Meningitis
Condition: Neoplastic Meningitis
MeSH terms: Meningeal Carcinomatosis; Meningitis
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Topotecan; Topotecan; Topotecan
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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.
Intervention MeSH terms: Topotecan
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: topotecan; pharmacokinetics; neoplastic; meningitis