Topotecan in Glioma Undergoing A Clinically-Indicated Surgical Resection

Study Overview
=================
Brief Summary
-----------------
Topotecan is an FDA-approved drug when given by intravenous infection. The purpose of this study is to determine if treatment with topotecan by an alternative method, direct delivery into the part of the brain where the tumor has spread, is safe and well tolerated. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan into tumor-infiltrated brain. A second purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan into tumor-infiltrated brain. This study will also examine how tumors responds to treatment with topotecan. This study will also look at the way topotecan is injected into tumors-infiltrated brain. A small amount of contrast dye (called gadolinium DTPA) will be added to topotecan before it is injected. Pictures will be taken of the brain with an MRI machine. This will allow the investigators to see where in the tumor-infiltrated brain the topotecan has been injected. This study will collect medical information before, during, and after treatment in order to better understand hot to make this type of procedure accessible to patients.

Detailed Description
-----------------
Primary Objectives To investigate by magnetic resonance (MR) imaging the spatial and temporal distribution of topotecan in tumor-infiltrated brain administered by convection-enhanced delivery (CED) in patients with recurrent/progressive WHO grade III or IV (high grade) glioma (HGG) who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy, following a clinically-indicated resection of the contrast enhancing tumor mass. To investigate by MR imaging the influence of catheter positioning, on the spatial and temporal distribution of topotecan administered by CED in patients with recurrent/progressive HGG To evaluate the extent of spatial distribution of topotecan, by MR imaging, when delivered into non-enhancing tumor tissue (as defined on pre-operative conventional MRI imaging with and without intravenous gadolinium) in the intraoperative setting, the immediate peri-operative setting, and in the post-operative setting. Secondary Objectives To investigate the extent to which CED-mediated delivery of topotecan To investigate the extent to which infusate can be distributed in the 2 cm margin around the resection cavity by administration by CED To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different infusion rates. To observe evidence of activity of single-agent topotecan administered by CED to patients with recurrent/progressive HGG who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy.

Official Title
-----------------
A Pilot Trial of Intraparenchymally-Administered Topotecan Using Convection-Enhanced Delivery (CED) in Patients With Suspected Recurrent/Progressive WHO Grade III or IV (High Grade) Glioma Undergoing A Clinically-Indicated Surgical Resection (IND 117,240)

Conditions
-----------------
Brain Tumor, High Grade Glioma

Intervention / Treatment
-----------------
* Drug: topotecan
* Device: Cleveland Multiport Catheter


Participation Criteria
=================
Eligibility Criteria
-----------------
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 surgical resection of the enhancing tumor is clinically indicated. Karnofsky Performance Status 70-100; MRI demonstration of an enhancing mass of more than 1 cm^3 and less than 100 cm^3; Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent; and Laboratory values within the following ranges: Absolute neutrophil count (ANC) ≥ 1,500 / μL; Platelet count ≥ 100,000 / μL; Hemoglobin ≥ 10 g / dL; Estimated glomerular filtration rate (eGFR) of at least 50 mL/min Exclusion Criteria: Patient 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 CSF disease; Tumors involving the cerebellum Active infection requiring treatment; Unexplained febrile illness; Radiation or chemotherapy within 4 weeks of enrollment Systemic diseases associated with unacceptable anesthesia or operative risk; Personal or family history of bleeding diathesis and a coagulation profile that would preclude patient from undergoing a neurosurgical procedure Subject must take anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery Inability to undergo magnetic resonance imaging.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intraparenchymally-administered topotecan<br>Patients will have topotecan administered directly into the tumor bed using convection-enhanced delivery (CED) | Drug: topotecan<br>* intraparenchymally-administered topotecan will use the Cleveland Multiport Catheter to directly infuse topotecan into the tumor site of patients with suspected recurrent/progressive high grade glioma (HGG). This drug is already FDA approved to be administered intravenously.<br>Device: Cleveland Multiport Catheter<br>* The Cleveland Multiport Catheter will directly infuse topotecan into the tumor site of patients with suspected recurrent/progressive high grade glioma (HGG). Standard treatment is to adminsiter the drug intravenously.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of number of adverse events by grade - A measure of treatment safety |  | up to 1 year after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with abnormal hematology lab reports |  | up to 1 year after start of treatment | 
| The number of patients with abnormal clinical chemistry lab reports |  | up to 1 year after start of treatment | 
| The number of patients with abnormal coagulation lab reports |  | up to 1 year after start of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Topotecan, Cleveland Multiport Catheter, Cancer