Focused Ultrasound BBBD for Glioblastoma

No longer recruiting at 16 trial locations

Overseen By Matt Hibert

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Inoperable tumors, Cardiac disease, Hypertension, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a focused ultrasound technique (Exablate Model 4000) to temporarily open the blood-brain barrier. This technique enables doctors to collect samples from brain tumors, specifically glioblastoma, for further study. Suitable candidates include those with a glioblastoma brain tumor that their doctor has identified for surgery or biopsy. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit future glioblastoma treatments.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications. However, if you are on anti-coagulant or anti-platelet therapy, you must stop these medications within a specific washout period before treatment: antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours.

Will I have to stop taking my current medications?

The trial requires stopping certain medications that increase the risk of bleeding. Specifically, you must stop antiplatelet or vitamin K inhibitor anticoagulants 7 days before treatment, non-vitamin K inhibitor anticoagulants 72 hours before, and heparin-derived compounds 48 hours before treatment.

What prior data suggests that this device is safe for blood brain barrier disruption?

Research shows that the Exablate Model 4000, a device used to temporarily open the brain's protective layer, has been studied for safety in patients with glioblastoma, a type of brain tumor. Previous studies found that patients generally tolerate this treatment well. The research focused on safely opening the brain's protective layer to improve tumor testing and treatment.

Some discomfort and side effects have been reported, but they are usually mild. Testing with patients in similar situations revealed that most did not experience serious problems. This suggests that the treatment could be safe for use in similar clinical settings.

As this treatment undergoes clinical trials, researchers continue to gather information on its safety and effectiveness. However, current research indicates that the Exablate Model 4000 seems to be a promising option for patients with glioblastoma. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Focused Ultrasound BBBD technique because it offers a novel way to treat glioblastoma by using ultrasound waves to temporarily open the blood-brain barrier. This method allows for more effective delivery of treatments directly to the brain, which is a significant improvement over traditional chemotherapy and radiation that struggle to penetrate this barrier. Unlike standard treatments, this technique could enhance the precision and efficacy of existing therapies, potentially leading to better outcomes for patients.

What evidence suggests that the Exablate Model 4000 is effective for blood brain barrier disruption in Glioblastoma?

Research has shown that focused ultrasound, such as the Exablate Model 4000, offers a promising method for treating glioblastoma by temporarily opening the blood-brain barrier. This trial will use the Exablate Model 4000 Type 2 to assess its effectiveness in facilitating liquid biopsy in subjects with glioblastoma. Early studies have indicated that this method can safely open the blood-brain barrier, which is crucial for delivering therapies directly to the tumor. Although this technology remains in the early stages, it offers hope for better outcomes in a condition that typically has a poor prognosis. Its precision and safety in targeting make it an important area of research for glioblastoma treatment. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults aged 18-80 with suspected glioblastoma brain tumors that can be targeted for surgery or biopsy are eligible. They must have a good performance status (Karnofsky Score >70) and be able to communicate during the procedure. Excluded are those with deep midline or multifocal tumors, certain heart conditions, uncontrolled hypertension, bleeding disorders, severe allergies, active infections including HIV, substance abuse issues, unstable mental health conditions at risk of suicide, and pregnant or breastfeeding women.

Inclusion Criteria

I am mostly able to care for myself but may not be able to do active work.

My brain scans show a tumor that can be targeted with precise radiation.

I am scheduled for surgery or a biopsy on my tumor within the next 4 weeks.

Exclusion Criteria

Abnormal coagulation profile (Platelets < 80,000), PT (>14) or PTT (>36), and INR > 1.3

MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices

Currently in a clinical trial involving an investigational product or non-approved use of a drug or device

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo blood-brain barrier disruption using Exablate Model 4000 for liquid biopsy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Exablate Model 4000

Trial Overview The trial is testing the safety and effectiveness of using Focused Ultrasound (Exablate Model 4000) to temporarily disrupt the blood-brain barrier in patients with suspected glioblastoma. This disruption aims to facilitate liquid biopsy—a less invasive method for analyzing tumor tissue.

How Is the Trial Designed?

Group I: Exablate BBBD Experimental Treatment 1 Intervention

Using Exablate Model 4000 Type 2 for liquid biopsy in subjects with Glioblastoma

Exablate Model 4000 is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Exablate Model 4000 Type 1.0 System for:

• Essential tremors
• Pain palliation of metastatic bone cancer
• Uterine fibroids

Approved in European Union as Exablate Neuro for:

• Essential tremors
• Uterine fibroids

Approved in Canada as Exablate Model 4000 Type 1.0 System for:

• Essential tremors
• Uterine fibroids

Approved in Japan as Exablate Neuro for:

• Uterine fibroids

Approved in China as Exablate Model 4000 Type 1.0 System for:

• Uterine fibroids

Who Is Running the Clinical Trial?

InSightec

Lead Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Published Research Related to This Trial

The first clinical experience with MRgFUS using the ExAblate 2100 system for non-invasive breast cancer showed promising results, with no severe adverse events reported in two patients.

Pathological examinations indicated that the treatment effectively induced tumor necrosis, suggesting that MRgFUS is a safe and feasible option for non-invasive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases. Matsutani, A., Ide, Y., Miura, S., et al.[2020]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

Three different ultrasound phantom models (cadaver, gel-filled skull, and full head phantom) were developed to improve the accuracy of transcranial MR-guided focused ultrasound (tcMRgFUS) for brain treatments, with the cadaver model showing the highest heating efficiency of 5.3 °C/(kW/s).

These phantoms provide valuable tools for research in tcMRgFUS, allowing for better understanding and optimization of thermal ablation techniques, with the cadaveric model being the most versatile despite practical limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head phantoms for transcranial focused ultrasound. Eames, MD., Farnum, M., Khaled, M., et al.[2019]

Focused ultrasound (FUS) combined with microbubbles can temporarily and noninvasively open the blood-brain barrier (BBB), which is crucial for improving the delivery of therapeutic agents to treat glioblastoma multiforme (GBM).

This method has shown enhanced delivery efficiency in various preclinical glioma models, suggesting it could significantly improve treatment outcomes for patients with GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Induced Blood-Brain-Barrier Opening Enhances Anticancer Efficacy in the Treatment of Glioblastoma: Current Status and Future Prospects. Deng, Z., Sheng, Z., Yan, F.[2020]

The ExAblate Neuro 4000 system uses Magnetic Resonance guided Focused UltraSound (MRgFUS) to precisely target and thermally ablate specific brain tissues, showing promise particularly in treating conditions like Essential Tremor.

Current clinical applications demonstrate that MRgFUS is both safe and effective, but ongoing advancements in technology are needed to enhance its efficacy and expand its use for various neurological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor. Jameel, A., Bain, P., Nandi, D., et al.[2021]

Diffuse Midline Glioma (DMG), previously known as Diffuse Intrinsic Pontine Glioma (DIPG), is a challenging pediatric brain tumor with no curative treatments available despite over 250 clinical trials.

Focused Ultrasound (FUS) is a promising noninvasive technology that can temporarily disrupt the blood-brain barrier, potentially allowing for better delivery of therapies and enhancing the effectiveness of treatments like chemotherapy and radiation for DMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. Parekh, K., LeBlang, S., Nazarian, J., et al.[2023]

The ExAblate 4000 system, designed for treating central nervous system disorders, successfully created thermal ablative lesions in all 22 swine subjects, demonstrating its efficacy in achieving targeted brain ablation with temperatures ranging from 52-65°C.

The procedure was well tolerated with minimal complications, such as incremental hemorrhage and necrosis, indicating a high safety margin for using MR-guided high-intensity focused ultrasound (MRgHIFU) in treating various cerebral pathologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonoablation and application of MRI guided focused ultrasound in a preclinical model. Zibly, Z., Graves, CA., Harnof, S., et al.[2014]

Magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to effectively and safely disrupt the blood-brain barrier (BBB), enhancing the delivery of various chemotherapeutic agents into brain tumors, as evidenced by preclinical studies and initial clinical trials.

The use of MRgFUS in glioma patients has demonstrated improved penetration of drugs like gadolinium across the BBB, indicating its potential to improve treatment outcomes, although further research is needed to fully understand drug distribution and effects on tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. Bunevicius, A., McDannold, NJ., Golby, AJ.[2022]

A 63-year-old patient with a recurrent glioblastoma underwent transcranial MR-guided focused ultrasound surgery (MRgFUS), demonstrating the feasibility of this noninvasive technique for brain tumor ablation.

The procedure involved 25 high-power sonications and successfully achieved partial tumor ablation without causing neurological deficits or adverse effects, highlighting its safety and potential for treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. Coluccia, D., Fandino, J., Schwyzer, L., et al.[2020]

This study demonstrated that repeated disruption of the blood-brain barrier (BBB) using MR-guided focused ultrasound (MRgFUS) is safe and feasible in patients with glioblastoma (GBM) undergoing standard chemotherapy with temozolomide, with no observed adverse effects during the treatment cycles.

Out of 145 BBBD trials conducted in 6 patients, 92.4% successfully showed evidence of BBB disruption on MRI, indicating that this method could enhance the delivery of therapeutic agents that are typically hindered by the BBB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. Park, SH., Kim, MJ., Jung, HH., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9021052/

Focused ultrasound for the treatment of glioblastoma - PMC Focused ultrasound is an early stage, therapeutic technology that offers possible adjuvant or alternative treatment strategies for glioblastoma (GBM).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03616860?term=NCT03616860&limit=10&rank=1

Assessment of Safety and Feasibility of ExAblate Blood ... 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) ...

3. academic.oup.com academic.oup.com/neuro-oncology/article/24/Supplement_7/vii82/6826182

CTNI-46. PIVOTAL STUDY TO EVALUATE SAFETY AND ... PIVOTAL STUDY TO EVALUATE SAFETY AND EFFICACY OF EXABLATE MODEL 4000 ... Glioblastoma (GBM) has dismal outcome of 14-16 months. One of the ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2101

A phase 1/2 dose escalation and expansion study of ... A phase 1/2 dose escalation and expansion study of sonodynamic therapy with SONALA-001 in combination with Exablate 4000 Type 2.0 MR-guided ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11538134/

Focused ultrasound-mediated enhancement of blood– ... ExAblate Neuro is an MR-guided hemispherical multi-element array, which has electronic steering capabilities and high targeting precision. The ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The warnings and precautions can be found in the ExAblate Neuro labeling (Information for. Prescribers and Operator's Manual). V. DEVICE ...