Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors
|ClinicalTrials.gov Identifier: NCT00112619|
Recruitment Status : Terminated (Slow accrual and company withdrawing support to supply the drug)
First Posted : June 3, 2005
Last Update Posted : June 30, 2011
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors Carcinoma of Unknown Primary Leukemia Lymphoma Unspecified Childhood Solid Tumor, Protocol Specific||Drug: topotecan hydrochloride||Phase 1|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis|
|Study Start Date :||August 2005|
|Actual Primary Completion Date :||August 2010|
- 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).Other Name: Hycamptin
- Estimate the maximum tolerated dose of intraventricular topotecan on this schedule [ Time Frame: First 14 days of therapy ]
- Number of patients with dose-limiting toxicity [ Time Frame: 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 [ Time Frame: Day 1 of Week 1 ]
- Number of patients with objective documentation of tumor response to intraventricular topotecan [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00112619
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Illinois|
|Children's Memorial Hospital - Chicago|
|Chicago, Illinois, United States, 60614|
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Dan L. Duncan Cancer Center at Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Study Chair:||Susan M. Blaney, MD||Baylor College of Medicine|