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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00025311
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : November 9, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
New York University School of Medicine

Brief 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.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: topotecan hydrochloride Phase 1

Detailed Description:


  • 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.

Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: A Phase I Study Of Seven Day Continuous Intrathecal/Intraventricular Infusion Of Topotecan For Patients With Recurrent, Progressive Or Refractory Leptomingeal Disease
Study Start Date : May 2001
Actual Primary Completion Date : October 2003

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Ages Eligible for Study:   up to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 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


  • 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)


  • Bilirubin no greater than 1.5 times normal
  • SGOT or SGPT less than 2.5 times upper limit of normal


  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min


  • Seizures allowed if well controlled and on anticonvulsants
  • CNS toxicity no greater than grade 2


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infections
  • HIV allowed


Biologic therapy:

  • No concurrent immunomodulating agents (stratum B)
  • No stem cell transplantation (stratum A)


  • 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


  • 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


  • Not specified


  • Recovered from prior therapy
  • At least 7 days since prior investigational drug
  • No other concurrent intrathecal or intraventricular therapy for leptomeningeal disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00025311

United States, New York
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
CHU Pitie-Salpetriere
Paris, France, 75651
Sponsors and Collaborators
New York University School of Medicine
National Cancer Institute (NCI)
Study Chair: Jonathan L. Finlay, MB, ChB New York University School of Medicine

Responsible Party: New York University School of Medicine Identifier: NCT00025311     History of Changes
Other Study ID Numbers: CDR0000068949
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: November 9, 2012
Last Verified: March 2003

Keywords provided by New York University School of Medicine:
leptomeningeal metastases

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents