Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier (BBB) Disruption in GBM Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of the Exablate Model 4000 Type 2.0 used as a tool to disrupt the BBB in patients with high grade glioma undergoing standard of care therapy.

Detailed Description
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The primary objective is to evaluate the safety and feasibility of BBB disruption using the Exablate Type 2.0 system in adult patients with glioblastoma (GBM) undergoing adjuvant TMZ chemotherapy, which occurs following maximal safe surgical resection and completion of the initial concurrent radiation-chemotherapy in accordance with the current standard of care

Official Title
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Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy

Conditions
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Glioma, Malignant, Glioblastoma

Intervention / Treatment
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* Device: Magnetic Resonance guided Focused ultrasound (MRgFUS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is eligible for adjuvant TMZ treatment. Men or women age between 18 and 80 years, inclusive. Able and willing to give informed consent. Grade IV glioma (GBM) confirmed Subjects Karnofsky rating 70-100. Able to communicate during the Exablate BBBD procedure. Life expectancy of at least 3 months. Exclusion Criteria: Evidence of acute intracranial hemorrhage. The subject presents with severe symptoms and signs of increased intracranial pressure Patients with cerebellar or brainstem tumors. Patients with positive HIV status Patients with brain tumors containing 1p/19q chromosomal co-deletion Patient receiving bevacizumab (Avastin) therapy Patients undergoing other concurrent therapies Cardiac disease or unstable hemodynamics Severe hypertension Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment History of a bleeding disorder and/or coagulopathy Known sensitivity to gadolinium-based contrast agents Known sensitivity to ultrasound contrast agent Severely impaired renal function Subjects with significant liver dysfunction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Focused Ultrasound (FUS) BBB Disruption<br>The Exablate Model 4000 Type 2.0 system is intended for use as a tool to induce localized and temporary blood-brain barrier disruption in patients with glioblastoma undergoing standard of care chemotherapy. | Device: Magnetic Resonance guided Focused ultrasound (MRgFUS)<br>* FUS involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct body targets.<br>* Other names: Exablate Neuro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device and procedure related adverse events | The number and severity of device and BBB disruption procedure related adverse events will be evaluated and classified according to the CTCAE | Throughout the study, approximately 12 months. | 
| Feasibility of repeated BBB disruption will be evaluated through assessment of post-procedure contrast-enhanced magnetic resonance (MR) imaging | The repeatability of BBB disruption will be evaluated at each of the 6 procedures and will be evaluated through assessment of post-procedure contrast-enhanced MR imaging. | At the time of each ExAblate MRgFUS procedure] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioma, MRgFUS, Exablate, TMZ