Topotecan in Treating Patients With Recurrent, Progressive, or Refractory Cancer That is Metastatic to the Lining Around the Brain

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I Study Of Seven Day Continuous Intrathecal/Intraventricular Infusion Of Topotecan For Patients With Recurrent, Progressive Or Refractory Leptomingeal Disease

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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: Stratum A: 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 Stratum B: 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

Ages Eligible for Study
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Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: topotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leptomeningeal metastases