GlioblastomaNCT03616860
Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier (BBB) Disruption for Treatment of Glioma
A study testing Focused Ultrasound (FUS) BBB Disruption in people with Glioblastoma, run by InSightec at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Focused Ultrasound (FUS) BBB Disruption
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- 16 Oct 2018to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- Patients presenting with the following imaging characteristics:
- Evidence of recent intracranial hemorrhage.
- The sonication pathway to the tumour involves:
- 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.
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- 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:
- 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.
- 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.
- Large subjects not fitting comfortably into the MRI scanner.
- Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.
- Untreated, uncontrolled sleep apnea.
- Positive pregnancy test (for pre-menopausal women).
- Known life-threatening systemic disease.
- Severely impaired renal function.
- Cardiac shunt.
- Previous full course of chemotherapy.
- 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 evidence of Hepatitis B virus infection/carrier state.
- Liver injury as indicated by liver function tests.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier Disruption for the Treatment of High Grade Glioma in Patients Undergoing Standard Chemotherapy
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.
Read the detailed description
This is a prospective, single center, single-arm study to establish the safety, feasibility, and effectiveness of BBB disruption along the periphery of the tumor resection cavity using the ExAblate Neuro Model 4000 Type 2 (220 kHz) system and DEFINITY ultrasound contrast in patients with GBM. Adult patients with a first time diagnosis of GBM, whom have undergone maximal safe surgical resection and have safely completed the initial phase of concurrent chemo-radiation therapy, will be recruited for this study. Twenty patients will undergo up to 6 treatments with FUS coincident with their standard TMZ cycles.
- Conditions
- Glioblastoma
- Being tested
- Focused Ultrasound (FUS) BBB Disruption
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focused Ultrasound (FUS) BBB DisruptionDevice
Also called Exablate Neuro
FUS BBB disruption involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct body targets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Focused Ultrasound (FUS) BBB Disruption |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
The repeatability of BBB disruption will be evaluated at each of the 6 procedures (coincident with standard of care chemotherapy) and will be evaluated through assessment of post-procedure contrast enhanced MR imaging.
Measured: Immediately after each FUS BBB disruption procedure
Effectiveness of BBB disruption in the treated tumor region
Effectiveness will be assessed based on the MRI characteristics of the FUS treated tumor region as assessed by the modified Response Assessment in Neuro-Oncology Criteria (RANO) to establish GBM status
Measured: at each standard of care neuro-oncology follow up visit until date of death from any cause, assessed up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start16 Oct 2018
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by InSightecThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nir Lipsman, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03616860
- Sponsor's protocol ID
- BT008C
- Other IDs
- 277981
- Status last verified
- Jan 2024
- First submitted
- 20 Jul 2018
- Last updated
- 23 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41308679Meng 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.
PubMed 33693781
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier Disruption for the Treatment of High Grade Glioma in Patients Undergoing Standard Chemotherapy
- ClinicalTrials.gov ID
- NCT03616860
- Acronym / sponsor ID
- BT008C
- Conditions
- Glioblastoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Study start
- 16 Oct 2018 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 6 Aug 2018 (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 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.
Detailed description
This is a prospective, single center, single-arm study to establish the safety, feasibility, and effectiveness of BBB disruption along the periphery of the tumor resection cavity using the ExAblate Neuro Model 4000 Type 2 (220 kHz) system and DEFINITY ultrasound contrast in patients with GBM. Adult patients with a first time diagnosis of GBM, whom have undergone maximal safe surgical resection and have safely completed the initial phase of concurrent chemo-radiation therapy, will be recruited for this study. Twenty patients will undergo up to 6 treatments with FUS coincident with their standard TMZ cycles.
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 (FUS) BBB Disruption | Experimental | Device: Focused Ultrasound (FUS) BBB DisruptionThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (34 listed)
- Patients presenting with the following imaging characteristics:
- The sonication pathway to the tumour 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 (FUS) BBB DisruptionAlso: Exablate NeuroFUS BBB disruption involves the application of acoustic energy at low frequencies from over 1000 individual transducers into distinct body targets | Device | Focused Ultrasound (FUS) BBB Disruption |
Primary outcome
Device and procedure related adverse events
Time frame: Throughout the study, approximately 12 months.
The number and severity of device and BBB disruption procedure related adverse events will be evaluated and classified according to the CTCAE
2 secondary outcomes
Feasibility of repeated BBB disruption will be evaluated through assessment of post-procedure contrast-enhanced magnetic resonance (MR) imaging
Time frame: Immediately after each FUS BBB disruption procedure
Effectiveness of BBB disruption in the treated tumor region
Time frame: at each standard of care neuro-oncology follow up visit until date of death from any cause, assessed up to 48 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Derived from this study: PubMed 41308679Woodworth 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.
- Derived from this study: PubMed 33693781Meng 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.
- 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. This study is not recruiting at the moment.
Nir Lipsman, MD 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 study testing Focused Ultrasound (FUS) BBB Disruption in people with Glioblastoma, run by InSightec 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 9 inclusion and 34 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: finished, as of the sponsor's last update on 23 Jan 2024. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device and procedure related adverse events (time frame: Throughout the study, approximately 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03616860, which also lists 2 linked publications.
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 23 Jan 2024.