Safety and Effectiveness of Blood-Brain Barrier Disruption (BBBD) in Subjects With Suspected Infiltrating Glioma (BBBD)

A Pivotal Study to Evaluate the Safety and Effectiveness of Exablate Model 4000 Using Microbubble Resonators to Temporarily Mediate Blood-Brain Barrier Disruption (BBBD) in Subjects With Suspected Infiltrating Glioma

The purpose of this study is to evaluate the safety and effectiveness of using the Exablate Type 2 system using microbubble resonators (Exablate Test Arm) to disrupt the Blood-Brain Barrier for the purpose of temporarily transforming, and thereby 'marking', regions of infiltrating gliomas prior to planned surgical resection, for the purpose of improving tumor visualization during the surgery to achieve a greater proportion of subjects who receive a Gross Total Resection (GTR) per plan compared to those not undergoing a BBBD procedure prior to resection (Control Arm).

Study Overview

• Status: Withdrawn
• Conditions: Glioma
• Intervention / Treatment: Device: Exablate BBBD

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo screening to determine eligibility for study entry. Patients who meet the eligibility requirements will be randomized in a 2:1 ratio to Exablate Test Arm and to Control Arm, respectively. The following assessments will occur:

1. Pre-surgical planning and Post-surgical visit MRI exams with and without contrast will be collected for evaluation by the study core lab; Any return to surgery for additional resection will be captured
2. All subjects will be seen at ~Week 2, and ~4-Weeks post resection for physical and neurological exams and to assess for complications or adverse events. These visits should coincide with standard (Neuro-oncology) care following resection.
3. Long-term outcomes will be collected during standard of care Neuro-oncology care follow-up visits for up to 2 years post resection; standard of care MRIs and RANO assessments will be collected.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or Female between 21-85 years of age who are able and willing to give informed consent
2. Subjects with suspected Grade II, III or IV infiltrating glioma (IG) on pre-operative brain imaging scans who have a non-enhancing component and are planned for surgical resection.
3. Karnofsky Performance Score 70-100
4. Able to communicate sensations during the Exablate BBBD procedure

Exclusion Criteria:

1. Tumor originating from the deep midline, thalamus, midbrain, cerebellum or brainstem.
2. Multifocal tumors

3. MRI or clinical findings of:

   1. Active or chronic infection(s) or inflammatory processes
   2. Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macro-hemorrhages
   3. Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis
4. More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
5. MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices

6. Significant cardiac disease or unstable hemodynamic status

   1. Documented myocardial infarction within six months of enrollment
   2. Unstable angina on medication
   3. Unstable or worsening congestive heart failure
   4. Left ventricular ejection fraction below the lower limit of normal
   5. History of a hemodynamically unstable cardiac arrhythmia
   6. Cardiac pacemaker
   7. Patient has right-to-left, bidirectional, or transient right-to-left cardiac shunts
   8. Subjects with relative contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation,
   9. Perflutren sensitivity or allergy ii. QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women)
7. Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication)
8. Unable to discontinue use of anti-coagulant/antiplatelet therapy as per local standard.
9. History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding
10. Abnormal coagulation profile (Platelets < 80,000), PT (>14) or PTT (>36), and INR > 1.3.
11. Large lacunar lesions that cannot be navigated around
12. Known cerebral or systemic vasculopathy
13. Significant depression and at potential risk of suicide
14. Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
15. Active seizures despite medication treatment (defined as >1 seizure per week) which could be worsened by disruption of the blood brain barrier
16. History of anaphylactic shock
17. Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning
18. Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis
19. Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess
20. Any contraindications to MRI scanning,
21. Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
22. Severe Respiratory Illness
23. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device
24. Pregnancy or Lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Exablate Test Arm; Subjects will undergo ExAblate BBBD prior to their standard of care tumor removal	Device: Exablate BBBD; Blood brain barrier disruption using ExAblate Type 2 device using microbubble resonators
No Intervention: Control Test Arm; Subjects will undergo their standard of care tumor removal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall safety of the Exablate BBBD procedure itself as measured through the collection of adverse events	Safety of the Exablate BBBD procedure will be evaluated by patient examination and post-procedure MRI exams assessing changes in the treated region. Adverse events will be reported by the Investigator and monitored in both treatment arms.	Approximately 2 months
Effectiveness of BBBD as determined by the proportion of subjects in whom a GTR is acheived	The proportion of subjects in whom a gross total resection (actual versus planned) is achieved as measured on post-operative imaging compared to pre-resection imaging	MRI 72 hours post resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmation of accuracy of Exablate BBBD targeting	Confirmation that new BBBD by contrast enhancement in a previously non-enhancing area overlies the intended target for BBBD. (ExAblate arm only)	MRI immediately after the ExAblate procedure
Return Rate for Second Surgery for Completion of Resection	Comparison of the Return Rate between the two treatment arms.	Approximately 2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of circulating tumor biomarkers	Collection of blood for evaluation of circulating tumor biomarkers (e.g. circulating tumor DNA [ctDNA])	pre- and post-BBBD procedure

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Actual): October 23, 2024
• Study Completion (Actual): October 23, 2024

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: BT011

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
• product manufactured in and exported from the U.S.: No