Focused Ultrasound Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy

NCT07179328 | Recruiting Phase 1

• 1 other identifier: GB-6232
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety and feasibility of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) disruption using the Next Generation Dome Helmet (NGDH) in adults with glioblastoma (GBM) undergoing the maintenance phase of the standard "Stupp protocol". Participants will:

• Undergo repeated FUS BBB disruption treatments during the maintenance phase of temozolomide (TMZ) chemotherapy.
• Receive intravenous ultrasound contrast (DEFINITY®) prior to each FUS session to facilitate targeted BBB disruption.
• Undergo serial MRI scans and clinical assessments to evaluate safety and the extent of BBB opening.
• Provide blood samples (and tumor tissue if available) for biomarker analysis related to BBB permeability, tumor presence, and treatment response.
• Be followed for progression-free survival (PFS) and overall survival (OS) during routine neuro-oncology visits until end of life.

Conditions

GBM; Glioblastoma Multiforme (GBM); Glioblastoma Multiforme of Brain; Glioblastoma Multiforme Glioma; HGG; Glioma; Brain Tumor Adult; Brain Tumor, Primary

Keywords

Focused Ultrasound; FUS; GBM; TMZ; Temozolomide; blood-brain barrier disruption (BBBD); MR-guided Focused Ultrasound (MRgFUS); Glioblastoma multiforme; blood-brain barrier opening; Drug delivery; Chemotherapy delivery

Outcome Measures

Primary Outcomes (1)

• Safety of Focused Ultrasound-Mediated BBB Disruption

  Safety will be evaluated by monitoring the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) related to FUS BBB disruption, graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Neurological assessments and MRI findings will be used to support safety evaluation.

  Participants will be evaluated at baseline, every 8 weeks during the first year, and every 12 weeks during the second year.

Secondary Outcomes (3)

• Clinical Efficacy - Radiographic Response (per modified RANO criteria)

  Participants will be evaluated at baseline, every 8 weeks during the first year, and every 12 weeks during the second year.

• Clinical Efficacy - Progression-Free Survival and Overall Survival

  Participants will be evaluated at baseline, every 8 weeks during the first year, and every 12 weeks during the second year.

• Clinical Efficacy - Comparison of liquid and tumour tissue biomarkers in relation to BBB disruption.

  Assessed at baseline and 1 day post-treatment for each of the 6 BBBD treatment cycles

Study Arms (1)

Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity

EXPERIMENTAL

Participants in this single-arm study will undergo repeated sessions (up to 6 cycles spaced 4-6 weeks apart) of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) disruption using the Next Generation Dome Helmet (NGDH) during the maintenance phase of standard-of-care temozolomide (TMZ) chemotherapy. At the time of each FUS session, participants will receive their prescribed standard of care TMZ dose, as well as an intravenous injection of DEFINITY® ultrasound contrast agent that enables targeted BBB opening. Each session will be guided by MRI, and imaging will be used to assess the extent of BBB disruption. Clinical and safety assessments, blood sampling for biomarker analysis, and follow-up imaging will be conducted throughout the study period.

Device: Focused Ultrasound Next Generation Dome Helmet; Drug: Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension

Interventions

Focused Ultrasound Next Generation Dome Helmet DEVICE

The Next Generation Dome Helmet (FUS NG) is a non-invasive, MRI-guided focused ultrasound system developed at Sunnybrook Research Institute. It is used to disrupt the blood-brain barrier (BBB) in patients with glioblastoma during the maintenance phase of temozolomide (TMZ) therapy. The device allows targeted BBB opening using a fixed transducer array and intravenous DEFINITY® contrast.

Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity

Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension DRUG

DEFINITY® Perflutren Injectable Microbubbles is an ultrasound contrast imaging agent that will be used for blood brain barrier opening during focused ultrasound. These microbubbles will be injected during the focused ultrasound procedure.

Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 85 years, inclusive.
• Able and willing to provide written informed consent.
• Diagnosis of Glioblastoma by histology or molecular markers based on WHO 2021 classification.
• Previously undergone a maximal safe surgical resection and completed concurrent, standard-of-care RT and TMZ without any complications and deemed eligible for the maintenance phase of TMZ treatment.
• Tumor or tumor resection cavity is clearly defined on screening MRI scans.
• Karnofsky Performance Score rating 70-100.
• American Society of Anesthesiologists (ASA) physical status score of 1-3.
• Life expectancy of at least 3 months and able to attend all study visits.

You may not qualify if:

• Patients presenting with the following imaging characteristics:
• i. Following steroid treatment, brain edema and/or mass effect that causes midline shift or shift in wall of the third ventricle of more than 10 mm.
• ii. Evidence of recent (less than 2 weeks) intracranial hemorrhage. iii. Calcifications in the FUS sonication beam path in the event system tools cannot tailor the treatment around these calcification spots.
• The sonication pathway to the tumor involves:
• i. 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.
• ii. Clips or other metallic implanted objects in the skull or the brain, except shunts.
• 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 with ≥25% increase in volume of contrast enhancement at time of assessment for study enrollment, compared with their first postoperative MRI. This cut-off is used to differentiate between pseudoprogression (which can occur following both radiation and TMZ therapy) and true tumor progression. This will be further ascertained through a discussion between the study neurosurgeons and radiologists.
• 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. These regimens have been shown to cause contrast enhancement in the resection cavity boundary, which can be difficult to differentiate from true tumor recurrence.
• 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 blood pressure (DBP) \> 100 on medication).
• Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment (i.e., antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours of treatment).

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Nir Lipsman

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nir Lipsman, MD, PhD, FRCSC

CONTACT

(416)-480-6954; Nir.Lipsman@sunnybrook.ca

Maheleth Llinas

CONTACT

416 480-6100; maheleth.llinas@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: September 17, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: September 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)