Exablate Blood-Brain Barrier Disruption for the Treatment of rGBM in Subjects Undergoing Carboplatin Monotherapy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and feasibility of the Exablate Model 4000 Type 2 system when used as a tool to open the blood-brain-barrier (BBB) in subjects with recurrent glioblastoma (rGBM) undergoing carboplatin monotherapy.

Detailed Description
-----------------
This is a Phase 1/2, open-label, prospective, multi-center, single-arm study to establish the safety and feasibility of blood-brain-barrier disruption (BBBD) combined with intravenous carboplatin for the treatment of rGBM using the Exablate Neuro Model 4000 Type 2 system with microbubble resonators. Adult glioblastoma subjects that are planned for carboplatin chemotherapy will be considered for study enrollment. Eligible subjects will undergo up to 6 cycles of Exablate BBBD procedures in conjunction with carboplatin chemotherapy.

Official Title
-----------------
Assessment of Safety and Feasibility of Exablate Type 2 for Blood-Brain Barrier Disruption (BBBD) With Microbubble Resonators for the Treatment of Recurrent Glioblastoma (rGBM) in Subjects Undergoing Carboplatin Monotherapy

Conditions
-----------------
Recurrent Glioblastoma

Intervention / Treatment
-----------------
* Drug: Carboplatin
* Device: Exablate BBBD


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be between 18-80 years old Histologically confirmed glioblastoma Planned for Carboplatin monotherapy Be willing and able to provided written informed consent/asent Tumor progression after first line chemo radiation Recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy Women of childbearing potential is confirmed not pregnant. Male and Female subjects utilize highly effective contraception Able to communicate verbally Exclusion Criteria: Acute intracranial hemorrhage Ferrous metallic implanted objects in the skull or brain Prior toxicity with carboplatin chemotherapy Women who are pregnant or breastfeeding Cerebellar spinal cord or brain stem tumor Known active Hepatitis B or Hepatitis C or HIV Significant depression not adequately controlled Has previously received anti-VEGF or anti-VEGF agents like Avastin Cardiac disease or unstable hemodynamics Severe hypertension History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage Active drug or alcohol use disorder Known sensitivity to gadolinium-based contrast agents Known sensitivity or contraindications to ultrasound contrast agent or perflutren Unable to undergo MRI or contraindications to MRI such as non-MRI compatible implanted devices Difficulty lying supine and still or severe claustrophobia which cannot be managed with medication Severely impaired renal function Right to left or bi-directional cardiac shunt Cranial or systemic infection requiring antibiotics Known additional malignancy that is progression or require active treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Exablate BBBD with carboplatin<br>Carboplatin will be administered via IV infusion about every 4 weeks for up to 6 cycles. The dosage will be calculated based on subject's creatinine level. On the day of planned carboplatin therapy, subjects will undergo Exablate procedure to open the blood-brain-barrier in the targeted cancerous brain areas prior to Carboplatin administration. | Drug: Carboplatin<br>* Carboplatin infusion on the day of Exablate BBBD procedure to treat cancerous cells in the brain<br>Device: Exablate BBBD<br>* BBB opening via Exablate Neuro Type 2 system with microbubble resonators.<br>* Other names: Exablate Neuro;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria. | Through study completion, an average of 12 months | 
| Contrast intensity on MR imaging | BBBD will be determined by contrast intensity in sonicated areas on T1 weighted gadolinium-based MR imaging | Immediately after Exablate BBBD procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exablate, Focused Ultrasound, rGBM