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

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
topotecan hydrochloride
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring leptomeningeal metastases

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • NYU School of Medicine's Kaplan Comprehensive Cancer Center
  • Herbert Irving Comprehensive Cancer Center
  • CHU Pitie-Salpetriere

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
October 11, 2001
Last Updated
November 8, 2012
Sponsor
NYU Langone Health
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00025311
Brief Title
Topotecan in Treating Patients With Recurrent, Progressive, or Refractory Cancer That is Metastatic to the Lining Around the Brain
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 Type
Interventional

2. Study Status

Record Verification Date
March 2003
Overall Recruitment Status
Completed
Study Start Date
May 2001 (undefined)
Primary Completion Date
October 2003 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
leptomeningeal metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride

10. Eligibility

Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan L. Finlay, MB, ChB
Organizational Affiliation
NYU Langone Health
Official's Role
Study Chair
Facility Information:
Facility Name
NYU School of Medicine's Kaplan Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
CHU Pitie-Salpetriere
City
Paris
ZIP/Postal Code
75651
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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