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.
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.
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.
Single group
Focused Ultrasound Next Generation Dome Helmet
DeviceThe 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.
Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension
DrugDEFINITY® 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.
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.
Clinical Efficacy - Radiographic Response (per modified RANO criteria)
Tumor response will be evaluated using MRI imaging and assessed according to modified Response Assessment in Neuro-Oncology (RANO) criteria.
Clinical Efficacy - Progression-Free Survival and Overall Survival
Comparing the PFS (by RANO 2.0 criteria) and Overall Survival (OS) of patients to historical controls.
Clinical Efficacy - Comparison of liquid and tumour tissue biomarkers in relation to BBB disruption.
Blood samples will be analyzed for BBB disruption and tumour-related biomarkers, including S100β protein, inflammatory cytokines, circulating DNA, exosomes, and circulating tumour cells. The specific biomarkers analyzed will be determined by the investigator based on sample availability.
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