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

NCT03616860 | Completed DMC

• 2 other identifiers: BT008C277981
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety of blood-brain barrier (BBB) disruption in adult patients with a first presentation of a glioblastoma (GBM) following a maximal safe surgical resection and standard chemo-radiation with temozolomide (TMZ) protocol and ready for the maintenance phase of the Stupp protocol with TMZ.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Feasibility of repeated BBB disruption will be evaluated through assessment of post-procedure contrast-enhanced magnetic resonance (MR) imaging

  Immediately after each FUS BBB disruption procedure

• Effectiveness of BBB disruption in the treated tumor region

  at each standard of care neuro-oncology follow up visit until date of death from any cause, assessed up to 48 months

Study Arms (1)

Focused Ultrasound (FUS) BBB Disruption

EXPERIMENTAL

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 standard of care chemotherapy.

Device: Focused Ultrasound (FUS) BBB Disruption

Interventions

Focused Ultrasound (FUS) BBB Disruption DEVICE

FUS BBB disruption involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct body targets

Also known as: Exablate Neuro

Focused Ultrasound (FUS) BBB Disruption

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women.
• Age between 18 and 80 years, inclusive.
• Able and willing to give informed consent.
• Grade IV malignant glioma (GBM) confirmed through assessment of surgical specimens by a board-certified neuropathologist.
• Undergone maximal safe surgical resection and completed concurrent radiotherapy+oral TMZ without any complications and deemed eligible for the maintenance phase of TMZ treatment.
• Karnofsky rating 70-100.
• ASA score 1-3.
• Able to communicate during the ExAblate MRgFUS procedure.
• Able to attend all study visits (i.e., life expectancy of at least 3 months).

You may not qualify if:

• Patients presenting with the following imaging characteristics:
• i. Evidence of recent intracranial hemorrhage.
• The sonication pathway to the tumour involves:
• i. Extensive scalp scars, ii. Clips or other metallic implanted objects in the skull or the brain (brain implants).
• The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
• Patients requiring increasing doses of corticosteroids.
• Patient receiving bevacizumab (Avastin) therapy.
• Patients undergoing other concurrent therapies such as chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, immunotherapies, and focal irradiation with brachytherapy, stereotactic radiosurgery, and laser interstitial thermotherapy.
• 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.
• Severe hypertension (diastolic BP \> 100 on medication).
• Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment.
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage.
• Documented cerebral infarction within the past 12 months.
• TIA in the last 1 month.

Sponsors & Collaborators

• InSightec: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (2)

• 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.

  PMID: 41308679 DERIVED

• Meng Y, Pople CB, Suppiah S, Llinas M, Huang Y, Sahgal A, Perry J, Keith J, Davidson B, Hamani C, Amemiya Y, Seth A, Leong H, Heyn CC, Aubert I, Hynynen K, Lipsman N. MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors. Neuro Oncol. 2021 Oct 1;23(10):1789-1797. doi: 10.1093/neuonc/noab057.

  PMID: 33693781 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Nir Lipsman, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: August 6, 2018
• Study Start: October 16, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)