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

NCT ID: NCT00025311

Last Updated: 2012-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-05-31

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

leptomeningeal metastases

Study Design

• Primary Study Purpose: TREATMENT

Interventions

topotecan hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan L. Finlay, MB, ChB

Role: STUDY_CHAIR

NYU Langone Health

Locations

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

CHU Pitie-Salpetriere

Paris, , France

Countries

United States; France

Other Identifiers

NYU-0005H

Identifier Type: -

Identifier Source: secondary_id

NYU-0041H

Identifier Type: -

Identifier Source: secondary_id

NCI-G01-2018

Identifier Type: -

Identifier Source: secondary_id

CDR0000068949

Identifier Type: -

Identifier Source: org_study_id