Intratumorally-Administered Topotecan Using Convection-Enhanced Delivery in Patients With Grade III/ IV Glioma

Study Overview
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Brief Summary
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The purpose of this study is to determine if treatment with Topotecan by an alternative method, delivering topotecan directly into brain tumors, is safe and well tolerated.

Official Title
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A Study of Intratumorally-Administered Topotecan Using Convection-Enhanced Delivery (CED) in Patients With Suspected Recurrent/Progressive World Health Organization (WHO) Grade III or IV (High Grade) Glioma Undergoing Stereotactic Biopsy

Conditions
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Glioma of Brain

Intervention / Treatment
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* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of supratentorial WHO Grade III or IV Glioma (High Grade Glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and a stereotactic biopsy is indicated for confirmation of recurrence/progression. 18 years of age or older Karnofsky Performance Status 70-100; MRI demonstration of a stereotactically accessible enhancing or predominantly non- enhancing mass that does not require resection to relieve clinically significant mass effect; Participant understands the procedures and agrees to comply with the study requirements by providing written informed consent Adequate organ function as indicated in protocol Exclusion Criteria: Participant is mentally or legally incapacitated at the time of the study; Known HIV(+) or has been diagnosed with AIDS Participation in another investigational drug study in the prior 4 weeks Positive pregnancy test in a female Patient, in the opinion of the investigator, is likely to be poorly compliant. Diffuse subependymal or Cerebral Spinal Fluid (CSF) disease Tumors involving the cerebellum Tumor enhancement involving both hemispheres Active infection requiring treatment Unexplained febrile illness Radiation or chemotherapy within 4 weeks of enrollment Systemic diseases associated with unacceptable anesthesia or operative risk Inability to undergo magnetic resonance imaging (MRI)

Ages Eligible for Study
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Minimum Age: 18 Years

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: Cleveland Multiport Catheter (CMC) + Topotecan<br>For predominantly enhanced tumors with volume of 8 cc or less, only 1 Cleveland Multiport Catheter (CMC) will be placed and convection-enhanced delivery (CED) will be performed over a 4-hour period within an MRI scanner, with the goal of complete tumor coverage (as evidenced by tracer distribution on MRI). The initial rate will be 1.20 ml/hour (5.0 microliters/minute/microcatheter) and infusion will be monitored by intermittent MRI imaging. The rate may be adjusted upwards during the infusion, in the event of incomplete tumor coverage, or downwards, if new mass effect is apparent. Following completion of the 4-hour infusion, the CMC will be removed. The initial rate for each subsequent patient may be adjusted upwards in increments of up to 5 microliters/minute/microcatheter based upon the tumor coverage and safety characteristics of the previously treated patients. | Drug: Topotecan<br>* Intratumorally-administered topotecan using convection-enhanced delivery (CED) in patients with suspected recurrent/progressive High Grade Glioma (HGG) requiring stereotactic biopsy and is focused on investigating topotecan brain tissue distribution and determining the safety, toxicity, and tolerability of intratumorally-administered topotecan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of topotecan in tumor tissue | The spatial distribution of intratumorally-administered topotecan will be determined using a gadolinium-based contrast agent, volumetric magnetic resonance imaging, and three-dimensional image reconstruction. | Treatment day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events (AEs) experienced by participants |  | Up to 48 weeks | 
| Extent of topotecan backflow | Investigate the extent to which backflow may be observed on MRI during CED-mediated delivery of topotecan | Treatment day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioma, Brain Tumor, High Grade Glioma