Safety Study of Intracerebral Topotecan for Recurrent Brain Tumors

Phase 1

• Conditions: Brain Neoplasms, Primary Malignant
• Interventions: Procedure: Convection-Enhanced Delivery; Drug: Topotecan

• Registration Number: NCT00308165
• Lead Sponsor: Jeffrey N. Bruce

Brief Summary

This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. This drug has been used for different types of cancer, but in this study it will be given by an experimental delivery technique designed to maximize the amount of drug delivered to the brain tumor and minimize the side effects in other parts of the body.

This study will also evaluate advanced magnetic resonance (MR) imaging techniques.

The study will assess quality of life parameters throughout the follow-up period.

Detailed Description

Clinical efficacy with chemotherapy has been discouraging for malignant brain tumors, mostly because of side effects and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (convection-enhanced delivery) is a novel drug delivery strategy that uses a microinfusion pump to establish a pressure gradient in the brain via implanted catheters. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding brain tissue.

Non-invasive magnetic resonance imaging (MRI) methods of monitoring drug distribution and treatment response have been developed to maximize the clinical applications and minimize complications associated with treatment risks.

Study participants will be taken to the operating room to have 2 catheters surgically placed into their tumor and surrounding tumor bed. These catheters will then be connected to small infusion pumps which will slowly infuse topotecan continuously over 4-5 days. Patients will have daily MRI scans while in the hospital. Upon completion of the experimental treatment, patients will be discharged and will be followed up in the outpatient clinic.

Study Timeline

• Study Start: 2004-03
• Study First Submitted: 2006-03-27
• Study First Submitted QC: 2006-03-27
• Study First Posted: 2006-03-29
• Primary Completion: 2011-09
• Status Verified: 2015-01
• Last Update Submitted: 2015-01-13
• Last Update Posted: 2015-01-15
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Single primary malignant brain tumor
• Previous treatment with external beam radiation
• Tumor is stereotactically accessible
• Karnofsky Performance Score of at least 60

Exclusion Criteria

• Diffuse subependymal or Cerebrospinal fluid (CSF) disease
• Tumor involves brainstem, cerebellum or both hemispheres
• Active infection
• Systemic disease associated with unacceptable anesthetic/operative risk
• Previous treatment with topotecan
• Unable to receive MRI scans

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Topotecan	Convection-Enhanced Delivery	Once a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months.
Topotecan	Topotecan	Once a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months.

Primary Outcome Measures

Name	Time	Method
Time to tumor progression/recurrence	treatment to progression
Time to death	Treatment to time of death
Grade 3 Adverse Events	during treatment, post treatment

Secondary Outcome Measures

Name	Time	Method
Quality of life at follow-up time points	pre-treatment, during treatment, post treatment

Trial Locations

Locations (1)

Columbia University Medical Center Neurological Institute; 🇺🇸 New York, New York, United States