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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025311
• Other study ID #: CDR0000068949
• Secondary ID: NYU-0005HNYU-004
• Status: Completed
• Phase: Phase 1
• First received: October 11, 2001
• Last updated: November 8, 2012
• Start date: May 2001

Study information

• Verified date: March 2003
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• topotecan hydrochloride

Locations

Country	Name	City	State
France	CHU Pitie-Salpetriere	Paris
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  France,