GBMPhase 1NCT07179328
Focused Ultrasound Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy
A Phase 1 study testing Focused Ultrasound Next Generation Dome Helmet and Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension in people with GBM and Glioblastoma Multiforme (GBM), run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial 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". Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- GBM, Glioblastoma Multiforme (GBM), Glioblastoma Multiforme of Brain
- What is being tested?
- Focused Ultrasound Next Generation Dome Helmet and Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 4 Jun 2025to Nov 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Patients presenting with the following imaging characteristics:
- 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.
- 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:
- 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.
- Clips or other metallic implanted objects in the skull or the brain, except shunts.
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- 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:
- 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).
- History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
- Abnormal level of platelets (< 100,000) or INR > 1.3.
- Documented cerebral infarction within the past 12 months.
- TIA in the last 1 month.
- Cerebral or systemic vasculopathy.
- Insulin-dependent diabetes mellitus that is not well-controlled or that in the Investigator's opinion precludes participation in the study.
- Known sensitivity to gadolinium-DTPA.
- Known sensitivity to DEFINITY® ultrasound contrast agent or perflutren.
- Contraindications to MRI such as non-MRI-compatible implanted devices, unable to tolerate an MRI due to for instance pain or claustrophobia, untreated, uncontrolled sleep apnea.
- Positive pregnancy test (for pre-menopausal women).
- Known life-threatening systemic disease.
- Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis.
- Right to left or bi-directional cardiac shunt.
- Previous full course of chemotherapy for GBM (at the discretion of investigator).
- Previous radiotherapy.
- Allergy to eggs or egg products.
- Subjects with evidence of cranial or systemic infection.
- Subjects with chronic pulmonary disorders.
- Subjects with a history of drug allergies, asthma or hay fever, and multiple allergies, in particular subjects with a history of anaphylaxis.
- Subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation, or QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women).
- Subjects with evidence of Hepatitis B virus infection/carrier state.
- Liver injury as indicated by liver function tests that in the Investigator's opinion precludes participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Nir Lipsman, MD, PhD, FRCSC, (416)-480-6954, Nir.Lipsman@sunnybrook.ca
Maheleth Llinas, 416 480-6100 ext. 2476, maheleth.llinas@sunnybrook.ca
About this study
Official title: Assessment of Safety and Feasibility of Focused Ultrasound Next Generational Dome Helmet Mediated Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy
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.
Read the detailed description
This is a Phase I, single-center, single-arm clinical trial. Approximately 10 participants are expected to be enrolled. The active therapy phase for participants will last approximately 6 to 8 months. Information about each participant's condition will continue to be collected for as long as possible to evaluate the effects of the therapy.
- Conditions
- GBM, Glioblastoma Multiforme (GBM), Glioblastoma Multiforme of Brain, Glioblastoma Multiforme Glioma, HGG, Glioma
- Being tested
- Focused Ultrasound Next Generation Dome Helmet, Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension
- 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
- Medical subject headings
- Glioblastoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focused Ultrasound Next Generation Dome HelmetDevice
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.
Definity® Vial for (Perflutren Lipid Microsphere) Injectable SuspensionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Focused Ultrasound Next Generation Dome Helmet; Drug: Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Tumor response will be evaluated using MRI imaging and assessed according to modified Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: 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
Comparing the PFS (by RANO 2.0 criteria) and Overall Survival (OS) of patients to historical controls.
Measured: 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.
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.
Measured: Assessed at baseline and 1 day post-treatment for each of the 6 BBBD treatment cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2025
- Study start4 Jun 2025
- Primary completionJul 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GBMStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Nir Lipsman, Sunnybrook Health Sciences Centre
- Investigators
- Nir Lipsman, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07179328
- Sponsor's protocol ID
- GB-6232
- Status last verified
- Jul 2025
- First submitted
- 13 Aug 2025
- Last updated
- 17 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Safety and Feasibility of Focused Ultrasound Next Generational Dome Helmet Mediated Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy
- ClinicalTrials.gov ID
- NCT07179328
- Acronym / sponsor ID
- GB-6232
- Conditions
- GBM, Glioblastoma Multiforme (GBM), Glioblastoma Multiforme of Brain, Glioblastoma Multiforme Glioma, HGG, Glioma
- Keywords
- Focused Ultrasound, FUS, GBM, TMZ, Temozolomide, blood-brain barrier disruption (BBBD), MR-guided Focused Ultrasound (MRgFUS), Glioblastoma multiforme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 4 Jun 2025 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 17 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase I, single-center, single-arm clinical trial. Approximately 10 participants are expected to be enrolled. The active therapy phase for participants will last approximately 6 to 8 months. Information about each participant's condition will continue to be collected for as long as possible to evaluate the effects of the therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity | Experimental | Device: Focused Ultrasound Next Generation Dome Helmet, Drug: Definity® Vial for (Perflutren Lipid Microsphere) Injectable SuspensionParticipants 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (37 listed)
- Patients presenting with the following imaging characteristics:
- The sonication pathway to the tumor involves:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Focused Ultrasound Next Generation Dome HelmetThe 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. | Device | Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity |
| Definity® Vial for (Perflutren Lipid Microsphere) Injectable SuspensionDEFINITY® 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. | Drug | Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity |
Primary outcome
Safety of Focused Ultrasound-Mediated BBB Disruption
Time frame: Participants will be evaluated at baseline, every 8 weeks during the first year, and every 12 weeks during the second year.
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.
3 secondary outcomes
Clinical Efficacy - Radiographic Response (per modified RANO criteria)
Time frame: 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
Time frame: 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.
Time frame: Assessed at baseline and 1 day post-treatment for each of the 6 BBBD treatment cycles
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nir Lipsman principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Focused Ultrasound Next Generation Dome Helmet and Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension in people with GBM and Glioblastoma Multiforme (GBM), run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nir Lipsman, MD, PhD, FRCSC ((416)-480-6954, Nir.Lipsman@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Focused Ultrasound-Mediated BBB Disruption (time frame: Participants will be evaluated at baseline, every 8 weeks during the first year, and every 12 weeks during the second year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2025.