Safety Study of Intracerebral Topotecan for Recurrent Brain Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors

Conditions
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Brain Neoplasms, Primary Malignant

Intervention / Treatment
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* Procedure: Convection-Enhanced Delivery
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topotecan<br>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. | Procedure: Convection-Enhanced Delivery<br>* microinfusion pumps to deliver chemotherapy directly into brain tumors<br>* Other names: Intracerebral Clysis;Drug: Topotecan<br>* chemotherapeutic drug for the treatment of brain tumors<br>* Other names: Hycamtin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life at follow-up time points |  | pre-treatment, during treatment, post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Primary Malignant Brain Tumors, Brain Tumors, Neoplasms, Brain, Brain Cancer, Brain cancer treatment, Topotecan