Phase I Study of Intrathecal Topotecan

Lymphoma Clinical Trial

Official title:

Phase I Study of Intrathecal Topotecan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001333
• Other study ID #: 930085
• Secondary ID: 93-C-0085
• Status: Completed
• Phase: Phase 1
• First received: November 3, 1999
• Last updated: March 3, 2008
• Start date: February 1993
• Est. completion date: December 2000

Study information

• Verified date: January 2000
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the qualitative and quantitative toxicity of intrathecal topotecan, a topoisomerase I inhibitor, in patients with meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy).

Description:

The purpose of this study is to determine the qualitative and quantitative toxicity of intrathecal topotecan, a topoisomerase I inhibitor, in patients with meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). A safe dose of topotecan that can be recommended for intrathecal administration in subsequent phase II studies will be established in a limited dosage escalation schedule. The CSF pharmacokinetics of intrathecal topotecan will also be studied. Topotecan will be administered intrathecally on a bi-weekly basis for four to six weeks, followed by weekly administration for 1 month, twice monthly administration for four months and then monthly IT administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

Leukemia, lymphoma, or solid tumor with overt meningeal involvement considered refractory to conventional therapy.

CSF leukemic cell count at least 5 per cubic millimeter with evidence of blast cells on cytospin or cytology required for leukemia and lymphoma patients.

Tumor cells on cytospin or cytology or measurable meningeal disease on CT or MRI required for patients with solid tumors.

No clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow as documented by indium-111- or technetium-99-DPTA flow study.

PRIOR/CONCURRENT THERAPY:

At least 1 week since CNS therapy.

Biologic Therapy: Recovery from toxic effects of prior immunotherapy required.

Chemotherapy:

Recovery from toxic effects of prior chemotherapy required.

No concomitant therapy to treat meningeal malignancy (intrathecal or systemic).

Concomitant chemotherapy to control systemic disease or bulk CNS disease allowed except:

Investigational agents. Agents that penetrate the CNS (e.g., high-dose methotrexate, thiotepa, high-dose cytarabine, fluorouracil, intravenous mercaptopurine).

Agents known to have serious unpredictable CNS side effects.

Endocrine Therapy: Not specified.

Radiotherapy: Recovery from toxic effects of prior radiotherapy required. Patient eligible if flow restored following focal radiotherapy to the blockage site.

Surgery: Not specified.

PATIENT CHARACTERISTICS:

Age: 3 and over (older patients giving consent will be enrolled before the very young, if possible).

Performance status: ECOG 0-2.

Life expectancy: At least 8 weeks.

Hematopoietic: See Disease Characteristics.

Hepatic: Bilirubin less than 2.0 mg/dL, SGPT less than 3 times normal.

Renal: Creatinine less than 1.5 mg/dL.

Metabolic: Serum electrolytes (including calcium and phosphate) normal.

Other: No significant systemic illness (e.g., infection). Not pregnant or lactating.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Meningeal Neoplasms

Intervention

Drug:
• topotecan

Locations

Country	Name	City	State
United States	National Cancer Institute (NCI)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Adamson PC, Balis FM, Arndt CA, Holcenberg JS, Narang PK, Murphy RF, Gillespie AJ, Poplack DG. Intrathecal 6-mercaptopurine: preclinical pharmacology, phase I/II trial, and pharmacokinetic study. Cancer Res. 1991 Nov 15;51(22):6079-83. — View Citation

Blaney SM, Balis FM, Cole DE, Craig C, Reid JM, Ames MM, Krailo M, Reaman G, Hammond D, Poplack DG. Pediatric phase I trial and pharmacokinetic study of topotecan administered as a 24-hour continuous infusion. Cancer Res. 1993 Mar 1;53(5):1032-6. — View Citation

Rowinsky EK, Grochow LB, Hendricks CB, Ettinger DS, Forastiere AA, Hurowitz LA, McGuire WP, Sartorius SE, Lubejko BG, Kaufmann SH, et al. Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. J Clin Oncol. 1992 Apr;10(4):647-56. — View Citation