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

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

The purpose of this study is to evaluate the safety of the ExAblate Model 4000 Type 2 used as a tool to disrupt the BBB (blood brain barrier) in patients with high grade glioma undergoing standard of care therapy.

Study Overview

• Status: Completed
• Conditions: Glioma; Glioblastoma
• Intervention / Treatment: Device: Focused ultrasound (FUS)

Detailed Description

This is a prospective, multi-center, single-arm study to establish the safety and feasibility of BBB (blood brain barrier) disruption along the periphery of tumor resection cavity using the ExAblate Neuro Model 4000 Type 2 (220 kHz) system. For this study, patients will be eligible to enroll in the study prior to beginning the planned adjuvant TMZ chemotherapy phase of treatment. Of note, only patients who are deemed eligible for adjuvant TMZ will be eligible for enrollment.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is eligible for adjuvant temozolomide (TMZ) treatment based on the current standard of care.
2. Men or women age between 18 and 80 years, inclusive.
3. Able and willing to give informed consent.
4. Grade IV glioma (GBM)
5. Combined radiation/TMZ treatment is completed based on the prescribed standard of care regimen.
6. Karnofsky rating 70-100.
7. Able to communicate during the ExAblate BBBD (Blood Brain Barrier Disruption) procedure.
8. Able to attend all study visits (i.e., life expectancy of at least 3 months).

Exclusion Criteria:

1. Patients presenting with the following imaging characteristics:

   i. Evidence of acute intracranial hemorrhage.

2. The sonication pathway to the tumor involves:

   i. Extensive scalp sores. ii. Clips or other metallic implanted objects in the skull or the brain (brain implants)

3. The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
4. Patients with cerebellar or brainstem tumors.
5. Patients with positive HIV status.
6. Significant depression not adequately controlled with medication and at potential risk of suicide.
7. Patient receiving bevacizumab (Avastin) therapy.
8. Patients receiving treatment with corticosteroid doses greater than dexamethasone 24 mg daily (or equivalent).
9. Patients undergoing other concurrent therapies such as chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, immunotherapies, focal irradiation with brachytherapy, stereotactic radiosurgery, laser interstitial thermotherapy, and tumor treatment fields therapy.

10. Cardiac disease or unstable hemodynamics including:

    i. Documented myocardial infarction within six months of enrollment. ii. Unstable angina on medication. iii. Congestive heart failure. iv. Left ventricular ejection fraction <50%. v. History of a hemodynamically unstable cardiac arrhythmia. vi. Cardiac pacemaker.

11. Severe hypertension (diastolic BP > 100 on medication).
12. Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment.
13. History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
14. Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis.
15. History of drug or alcohol use disorder.
16. Active seizure disorder or epilepsy (seizures despite medical treatment).
17. Known sensitivity to gadolinium-based contrast agents.
18. Known sensitivity to DEFINITY® ultrasound contrast agent or perflutren.
19. Contraindications to MRI such as non-MRI-compatible implanted devices.
20. Large subjects not fitting comfortably into the MRI scanner.
21. Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.
22. Positive pregnancy test (women of childbearing potential).
23. Severely impaired renal function or on dialysis.
24. Cardiac shunt.
25. Subjects with evidence of cranial or systemic infection.
26. Subjects with significant liver dysfunction, e.g., history of cirrhosis or active hepatitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Focused Ultrasound (FUS); The ExAblate Model 4000 Type 2 system is intended for use as a tool to induce localized and temporary blood-brain barrier disruption in patients with glioblastoma undergoing initial standard of care chemotherapy.	Device: Focused ultrasound (FUS); FUS involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct body targets.; Other Names: ExAblate, Type 2

What is the study measuring?

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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: InSightec
• Investigators: Principal Investigator: Graeme Woodworth, MD, University of Maryland

Publications and helpful links

General Publications

• Woodworth GF, Anastasiadis P, Ozair A, Chabros J, Bettegowda C, Chen C, Gerstl JVE, Douville C, Mekary RA, Smith TR, Meng Y, Hawkins C, Pople CB, Abrahao A, Llinas M, Heyn C, Bunevicius A, Rezai AR, Ball AJS, Henry K, Sahgal A, Torio E, Ren H, Ahmad H, Arora H, Eisenberg H, Perry J, Carpenter JS, Hynynen K, Pham LC, Anketell MB, Lim-Fat MJ, Xu Z, Cifarelli CP, Sheehan JP, McDannold NJ, Gandhi D, Golby AJ, Lipsman N. Microbubble-enhanced transcranial focused ultrasound with temozolomide for patients with high-grade glioma (BT008NA): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2025 Dec;26(12):1651-1664. doi: 10.1016/S1470-2045(25)00492-9.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma
• Other Study ID Numbers: BT008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes