Glioblastoma MultiformeNCT03712293
ExAblate Blood-Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy
A study testing BBB Disruption with Chemotherapy Arm in people with Glioblastoma Multiforme, run by InSightec at 1 site in South Korea.
Trial summary
The purpose of this study is to evaluate the safety of the ExAblate Model 4000 Type 2.0 used as a tool to disrupt the BBB in patients with Glioblastoma undergoing standard of care therapy. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- BBB Disruption with Chemotherapy Arm
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteSouth Korea
- Study dates
- 28 Aug 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is eligible for adjuvant TMZ treatment based on the current standard of care.
- Men or women.
- Age between 19 and 80 years, inclusive.
- Able and willing to give informed consent.
- Grade IV glioma (GBM) confirmed through assessment of surgical specimens by a board-certified neuropathologist.
- Combined radiation/TMZ treatment is completed based on the prescribed standard of care regimen.
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- Karnofsky rating 70-100 (See Appendix B).
- Able to communicate during the ExAblate BBBD procedure.
- Able to attend all study visits (i.e., life expectancy of at least 3 months).
Who cannot join
- 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.
- The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
- Patients with cerebellar or brainstem tumors.
- Patient receiving bevacizumab (Avastin) therapy.
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- Patients receiving treatment with corticosteroid doses greater than dexamethasone 16mg daily (or equivalent).
- Patients undergoing other concurrent therapies such as chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, immunotherapies, focal irradiation with brachytherapy, stereotactic radiosurgery, laser interstitial thermotherapy, and tumor treatment fields therapy. These regimens have been shown to cause contrast enhancement in the resection cavity boundary, which can be difficult to differentiate from true tumor recurrence [35] [36], [37-39].
- 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 (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.
- Cerebral or systemic vasculopathy.
- Evidence of new focal neurological deficits including, but not limited to, motor weakness or speech impairment within 7-14 days prior to the first BBBD procedure.
- History of drug or alcohol use disorder.
- Active seizure disorder or epilepsy (seizures despite medical treatment).
- Known sensitivity to gadolinium-based contrast agents.
- 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.
- Positive pregnancy test (women of childbearing potential).
- 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.
- Subjects with evidence of cranial or systemic infection.
- 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).
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Severance Hospital, Yonsei University Health System
Seoul, Seodaemun-gu, 03722
About this study
Official title: Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier Disruption for the Treatment of Glioblastoma in Patients Undergoing Standard Chemotherapy
The purpose of this study is to evaluate the safety of the ExAblate Model 4000 Type 2.0 used as a tool to disrupt the BBB in patients with Glioblastoma undergoing standard of care therapy.
Read the detailed description
This is a prospective, multisingle-center, single-arm study to establish the safety and feasibility of BBB disruption along the periphery of tumor resection cavity using the ExAblate Neuro Model 4000 Type 2.0 (220 kHz) system. For this study, patients will be eligible to enroll in the study prior to beginning the planned adjuvant TMZ chemotherapy phase of treatment. Of note, only patients who are deemed eligible for adjuvant TMZ will be eligible for enrollment. This study will enroll up to 20 subjects.
- Conditions
- Glioblastoma Multiforme
- Being tested
- BBB Disruption with Chemotherapy Arm
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BBB Disruption with Chemotherapy ArmDevice
The ExAblate BBB disruption of targets associated with enhancing post-resection MRI imaging procedure will be performed with ExAblate 4000 type 2.0 system and will coincide with on one of three first days of each planned TMZ adjuvant therapy cycle as one procedure per cycle.
| Study group | Role | What they receive |
|---|---|---|
| BBB Disruption with Chemotherapy Arm | Experimental | All subjects in this arm will undergo ExAblate Type 2.0 BBBD procedures on one of the first three days of each TMZ dosing cycle throughout the adjuvant phase (up to 6 cycles). Receives: Device: BBB Disruption with Chemotherapy Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events Safety Profile
The type and severity of adverse events post-procedure will be assessed for overall safety. Safety of the BBBD procedure will be evaluated through patient examination and MRI assessments during the treatment and by their standard of care follow-up MRI scans and clinical visits. The standard of care follow-up MRI scans will be used to continue safety monitoring post-BBBD procedures and after adjuvant TMZ chemotherapy is completed.
Measured: 7 months
Secondary outcomes (1)
Blood Brain Barrier Opening
The ability to open the Blood Brain Barrier with ExAblate Focused Ultrasound will be evaluated by contrast MR imaging. If the procedure was successful, the area treated with show contrast enhancement on MRI.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start28 Aug 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 Glioblastoma MultiformeStudies 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
- Model description
- This study will enroll up to 10 patients who are eligible and recommended for the standard adjuvant phase of TMZ chemotherapy. The goal is for all subjects to undergo ExAblate Type 2.0 BBB disruption procedures on one of the first three days of each TMZ dosing cycle throughout the adjuvant phase (up to 6 cycles).
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Martin Bernstein, Study director, InSightec
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03712293
- Sponsor's protocol ID
- BT008K
- Status last verified
- Mar 2024
- First submitted
- 16 Oct 2018
- Last updated
- 5 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. One-Year Outcome of Multiple Blood-Brain Barrier Disruptions With Temozolomide for the Treatment of Glioblastoma. Front Oncol. 2020 Sep 10;10:1663. doi: 10.3389/fonc.2020.01663. eCollection 2020.
PubMed 33014832Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J Neurosurg. 2020 Jan 3;134(2):475-483. doi: 10.3171/2019.10.JNS192206. Print 2021 Feb 1.
PubMed 31899873
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 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 Glioblastoma in Patients Undergoing Standard Chemotherapy
- ClinicalTrials.gov ID
- NCT03712293
- Acronym / sponsor ID
- BT008K
- Conditions
- Glioblastoma Multiforme
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Study start
- 28 Aug 2018 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 19 Oct 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 the ExAblate Model 4000 Type 2.0 used as a tool to disrupt the BBB in patients with Glioblastoma undergoing standard of care therapy.
Detailed description
This is a prospective, multisingle-center, single-arm study to establish the safety and feasibility of BBB disruption along the periphery of tumor resection cavity using the ExAblate Neuro Model 4000 Type 2.0 (220 kHz) system. For this study, patients will be eligible to enroll in the study prior to beginning the planned adjuvant TMZ chemotherapy phase of treatment. Of note, only patients who are deemed eligible for adjuvant TMZ will be eligible for enrollment. This study will enroll up to 20 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study will enroll up to 10 patients who are eligible and recommended for the standard adjuvant phase of TMZ chemotherapy. The goal is for all subjects to undergo ExAblate Type 2.0 BBB disruption procedures on one of the first three days of each TMZ dosing cycle throughout the adjuvant phase (up to 6 cycles).
| Arm | Type | Receives |
|---|---|---|
| BBB Disruption with Chemotherapy Arm | Experimental | Device: BBB Disruption with Chemotherapy ArmAll subjects in this arm will undergo ExAblate Type 2.0 BBBD procedures on one of the first three days of each TMZ dosing cycle throughout the adjuvant phase (up to 6 cycles). |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient is eligible for adjuvant TMZ treatment based on the current standard of care.
- Men or women.
- Age between 19 and 80 years, inclusive.
- Able and willing to give informed consent.
- Grade IV glioma (GBM) confirmed through assessment of surgical specimens by a board-certified neuropathologist.
Key exclusion criteria (27 listed)
- 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 with cerebellar or brainstem tumors.
- Patient receiving bevacizumab (Avastin) therapy.
- Patients receiving treatment with corticosteroid doses greater than dexamethasone 16mg daily (or equivalent).
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 |
|---|---|---|
| BBB Disruption with Chemotherapy ArmThe ExAblate BBB disruption of targets associated with enhancing post-resection MRI imaging procedure will be performed with ExAblate 4000 type 2.0 system and will coincide with on one of three first days of each planned TMZ adjuvant therapy cycle as one procedure per cycle. | Device | BBB Disruption with Chemotherapy Arm |
Primary outcome
Adverse Events Safety Profile
Time frame: 7 months
The type and severity of adverse events post-procedure will be assessed for overall safety. Safety of the BBBD procedure will be evaluated through patient examination and MRI assessments during the treatment and by their standard of care follow-up MRI scans and clinical visits. The standard of care follow-up MRI scans will be used to continue safety monitoring post-BBBD procedures and after adjuvant TMZ chemotherapy is completed.
1 secondary outcome
Blood Brain Barrier Opening
Time frame: 7 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 5 Mar 2024.
- Derived from this study: PubMed 33014832Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. One-Year Outcome of Multiple Blood-Brain Barrier Disruptions With Temozolomide for the Treatment of Glioblastoma. Front Oncol. 2020 Sep 10;10:1663. doi: 10.3389/fonc.2020.01663. eCollection 2020.
- Derived from this study: PubMed 31899873Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J Neurosurg. 2020 Jan 3;134(2):475-483. doi: 10.3171/2019.10.JNS192206. Print 2021 Feb 1.
- 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.
Martin Bernstein study director
InSightec
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BBB Disruption with Chemotherapy Arm in people with Glioblastoma Multiforme, run by InSightec at 1 site in South Korea.
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 27 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 5 Mar 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 South Korea. 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?
Adverse Events Safety Profile (time frame: 7 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 NCT03712293, 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 5 Mar 2024.