Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors
- Conditions
- Brain and Central Nervous System TumorsLymphomaLeukemiaUnspecified Childhood Solid Tumor, Protocol SpecificCarcinoma of Unknown Primary
- Registration Number
- NCT00112619
- Lead Sponsor
- Pediatric Brain Tumor Consortium
- Brief 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Number of patients with dose-limiting toxicity First 14 days of therapy Estimate the dose of intraventricular topotecan that will result in cerebrospinal fluid lactone concentrations exceeding 1 ng/mL for at least 8 hours after an intrathecal injection Day 1 of Week 1 Estimate the maximum tolerated dose of intraventricular topotecan on this schedule First 14 days of therapy
- Secondary Outcome Measures
Name Time Method Number of patients with objective documentation of tumor response to intraventricular topotecan Weeks 5, 11 and then every 12 weeks until off study MRI of the brain and spine is obtained pre-consolidation, pre-maintenance, and then every 12 weeks in maintenance.
Pharmacokinetics Day 1 of Week 1 The cerebrospinal fluid (CSF) concentration-time profile for topotecan after intrathecal CSF administration will be modeled from the CSF samples collected on day 1 of week 1. Individual pharmacokinetic parameters estimated will include volume of central compartment, elimination rate constant, half-life, and clearance.
Correlation of imaging parameters with tumor response Pre-treatment, week 5, week 11, and then every 12 weeks until off study MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.
Trial Locations
- Locations (11)
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Dan L. Duncan Cancer Center at Baylor College of Medicine
🇺🇸Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
🇺🇸Bethesda, Maryland, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States