Progressive Locomotor Ataxia |
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Clinical Trial: Topotecan in Treating Patients With Recurrent, Progressive, or Refractory Cancer That is Metastatic to the Lining Around the Brain
This study is no longer recruiting patients.
Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of intrathecal or intraventricular topotecan in treating recurrent, progressive, or refractory cancer that is metastatic to the lining around the brain.
| Condition | Treatment or Intervention | Phase |
|---|---|---|
| leptomeningeal metastases | Drug: topotecan Procedure: chemotherapy | Phase I |
MedlinePlus related topics: Cancer; Cancer Alternative Therapy; Neurologic Diseases
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of Intrathecal or Intraventricular Topotecan in Patients With Recurrent, Progressive, or Refractory Leptomeningeal Disease
OBJECTIVES:
- Determine the maximum tolerated dose of intrathecal or intraventricular topotecan in patients with recurrent, progressive, or refractory leptomeningeal disease.
- Determine the toxicity of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the anti-tumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to disease (leukemia or lymphoma vs solid tumor or other malignancy).
Patients receive topotecan intrathecally or intraventricularly continuously on days 1-7. Treatment repeats every 21 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose- limiting toxicity.
Patients are followed for 6 months.
PROJECTED ACCRUAL: A maximum of 50 patients (25 per stratum) will be accrued for this study.
Eligibility
Ages Eligible for Study: up to 65 Years, Genders Eligible for Study: Both
Criteria
DISEASE CHARACTERISTICS:
- Histologic or tumor marker confirmation of malignancy at original diagnosis
- Neoplastic meningitis/leptomeningeal metastasis refractory to conventional therapy and other therapies of higher priority, defined as:
- Small non-cleaved lymphoma (Burkitt's) with any L-3 blast in cerebrospinal fluid (CSF)
- Any other lymphoma or leukemia with CSF cell count greater than 5/mm3 AND evidence of blast cells by cytology or cytospin preparation OR
- Solid tumor or other malignancy with presence of tumor cells on cytospin OR positive cytology OR neuroimaging evidence of leptomeningeal tumor by MRI or CT myelogram
- No leptomeningeal leukemia or lymphoma with concurrent bone marrow relapse
- No clinical evidence of untreated obstructive hydrocephalus or compartmentalization of the CSF
PATIENT CHARACTERISTICS: Age:
- 65 and under
Performance status:
- Lansky 50-100% (age 16 and under)
- Karnofsky 50-100% OR ECOG 0-3 (over age 16)
Life expectancy:
- At least 2 months
Hematopoietic:
- Stratum B:
- Absolute neutrophil count at least 750/mm^3
- Platelet count at least 75,000/mm^3 (transfusion independent)
- Hemoglobin at least 10.0 g/dL (red blood cell transfusions allowed)
Hepatic:
- Bilirubin no greater than 1.5 times normal
- SGOT or SGPT less than 2.5 times upper limit of normal
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
Neurologic:
- Seizures allowed if well controlled and on anticonvulsants
- CNS toxicity no greater than grade 2
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infections
- HIV allowed
PRIOR CONCURRENT THERAPY: Biologic therapy:
- No concurrent immunomodulating agents (stratum B)
- No stem cell transplantation (stratum A)
Chemotherapy:
- At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas)
- No other concurrent cancer chemotherapy (stratum B)
- Other concurrent systemic cancer chemotherapy for leukemia or lymphoma allowed with the following restrictions:
- No oral or IV topotecan
- No moderate or high-dose IV or subcutaneous cytarabine (greater than 1.0 g/m2 per day)
- No moderate or high-dose IV methotrexate (greater than 1 g/m2 per day)
- No IV thiotepa
- No myeloablative chemotherapy
- No intrathecal or intraventricular chemotherapy
Endocrine therapy:
- Concurrent corticosteroids allowed only for treatment of increased intracranial pressure in patients with CNS tumors
- No concurrent intrathecal or intraventricular hydrocortisone
Radiotherapy:
- At least 4 weeks since completion of radiotherapy to the brain or spine and recovered
- Concurrent radiotherapy to localized painful lesions producing acute neurologic dysfunction allowed provided at least 1 measurable lesion is not irradiated
- No concurrent craniospinal or whole-brain radiotherapy
Surgery:
- Not specified
Other:
- Recovered from prior therapy
- At least 7 days since prior investigational drug
- No other concurrent intrathecal or intraventricular therapy for leptomeningeal disease
Location Information
New York
Herbert Irving Comprehensive Cancer Center, New York, New York, 10032, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York, 10016, United States
France
CHU Pitie-Salpetriere, Paris, 75651, France
Jonathan L. Finlay, M.B., Ch.B., Study Chair, Kaplan Cancer Center
More Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Record last reviewed: April 2003
Last Updated: October 13, 2004
Record first received: October 11, 2001
ClinicalTrials.gov Identifier: NCT00025311
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08
Source: ClinicalTrials.gov
Cache Date: April 9, 2005
Resources
- Progressive Locomotor Ataxia (National Institute of Neurological Disorders and Stroke)

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