Focused Ultrasound BBBD for Glioblastoma

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

57 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of using the Exablate device to temporarily open the blood-brain barrier in patients with suspected Glioblastoma. By doing this, doctors can collect fluid from the brain to check for cancer cells. The study will take place at up to 25 centers in the US.

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 data supports the idea that Focused Ultrasound BBBD for Glioblastoma is an effective treatment?

The available research does not provide specific data on the effectiveness of Focused Ultrasound BBBD for Glioblastoma. However, it does highlight the potential of this treatment in other brain-related conditions. For example, the ExAblate Neuro 4000 system has been used effectively for essential tremor, a condition that causes uncontrollable shaking. This suggests that the technology can precisely target areas in the brain, which could be beneficial for treating glioblastoma. Additionally, the treatment has been shown to help deliver drugs more effectively into brain tumors by temporarily opening the blood-brain barrier, which is a protective shield around the brain. This could potentially make chemotherapy more effective for glioblastoma patients. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Exablate Model 4000, Exablate Model 4000 Type 1.0 System, Exablate Neuro, MRgFUS System for glioblastoma?

The Exablate Neuro 4000 system, part of the MRgFUS technology, has shown promise in treating various brain conditions by precisely targeting and disrupting the blood-brain barrier, which can help deliver treatments directly to brain tumors. This technology has been effective in other conditions like essential tremor and is being explored for its potential in enhancing chemotherapy delivery for brain tumors. ^{1 2 3 4 5}

What safety data exists for focused ultrasound BBBD treatment for glioblastoma?

The ExAblate Neuro 4000 system, used for MR-guided focused ultrasound (MRgFUS), has been evaluated for safety in various studies. It has been used successfully for essential tremor and brain tumor ablation, including glioblastoma, without causing neurological deficits or adverse effects. Preclinical models using the ExAblate 4000 system demonstrated high safety margins with minimal hemorrhage and necrosis. A study specifically on glioblastoma patients undergoing standard chemotherapy found that repeated blood-brain barrier disruptions with MRgFUS were safe and feasible. ^{1 3 6 7 8}

Is focused ultrasound treatment generally safe for humans?

Focused ultrasound treatment, using systems like ExAblate Neuro 4000, has been shown to be safe in humans for various conditions, including essential tremor and brain tumors. Studies have demonstrated that it can be used without causing significant adverse effects, such as neurological deficits, and is well-tolerated in both human and animal models. ^{1 3 6 7 8}

Is the Exablate Model 4000 treatment promising for glioblastoma?

Yes, the Exablate Model 4000 treatment is promising for glioblastoma. It uses focused ultrasound to temporarily open the blood-brain barrier, allowing chemotherapy drugs to reach the tumor more effectively. This approach has shown potential in increasing the effectiveness of cancer treatments and is considered safe and feasible. ^{1 3 8 9 10}

How is the Focused Ultrasound BBBD treatment for glioblastoma different from other treatments?

The Focused Ultrasound BBBD treatment for glioblastoma is unique because it uses sound waves to temporarily open the blood-brain barrier, allowing chemotherapy drugs to reach the tumor more effectively. This non-invasive approach is different from traditional treatments that struggle to deliver drugs past the blood-brain barrier. ^{1 3 8 9 10}

Eligibility Criteria

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.

I am between 18 and 80 years old and can consent to treatment.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Head phantoms for transcranial focused ultrasound. [2019]

3. Germany 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. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. [2020]

7. Scotland pubmed.ncbi.nlm.nih.gov

Sonoablation and application of MRI guided focused ultrasound in a preclinical model. [2014]

8. United States 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. [2023]

9. United States 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. [2023]

10. Egypt pubmed.ncbi.nlm.nih.gov

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