Focused Ultrasound for Brain Tumor

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Anticoagulants, NSAIDs, Statins

Disqualifiers: Cardiac disease, Severe hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial excludes participants on anti-coagulant therapy or medications that increase the risk of bleeding, like NSAIDs and statins. If you're taking these, you may need to stop, but the protocol doesn't specify a washout period.

What data supports the effectiveness of the treatment Transcranial ExABlate for brain tumors?

Focused ultrasound, like Transcranial ExABlate, is a non-invasive treatment that can help treat brain tumors by using sound waves to target and destroy tumor cells. It has shown promise in allowing medications to reach the brain more effectively by temporarily opening the blood-brain barrier, which is a protective shield around the brain. ^{1 2 3 4 5}

Is focused ultrasound for brain tumors safe for humans?

Focused ultrasound for brain tumors has been shown to be safe in various studies, with some patients experiencing mild and temporary side effects like headaches and nausea. Clinical trials have demonstrated that it can safely open the blood-brain barrier and ablate tumor tissue without causing neurological deficits or other serious adverse effects. ^{4 6 7 8 9}

How does the Transcranial ExABlate treatment for brain tumors differ from other treatments?

Transcranial ExABlate uses focused ultrasound, a non-invasive technique that targets brain tumors with sound waves to destroy them or open barriers for drug delivery, unlike traditional surgery or chemotherapy that can be invasive and have toxic effects on healthy tissue. ^{1 4 10 11 12}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety of BBB disruption using transcranial MRI-guided focused ultrasound in conjunction with an intravenous ultrasound contrast agent to increase the accumulation of doxorubicin in brain tumours and the adjacent brain using the ExAblate Transcranial system (220 kHz). Data will be collected to establish the basic safety of this type of treatment as the basis for later studies to evaluate its clinical efficacy.

Eligibility Criteria

This trial is for adults aged 18-70 with brain tumors smaller than 2.5 cm in diameter, who can attend all visits and have a life expectancy of at least 3 months. Participants must be able to communicate during the procedure, have not had brain surgery within the last two weeks, and are generally in good health as indicated by Karnofsky rating and ASA score.

Inclusion Criteria

I am mostly independent and can care for myself.

Able to communicate sensations during the ExAblate MRgFUS procedure.

Able to attend all study visits (i.e., life expectancy of at least 3 months).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo blood-brain barrier disruption using transcranial MRI-guided focused ultrasound with intravenous ultrasound contrast agents to increase doxorubicin accumulation in brain tumours

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the ExAblate transcranial procedure

4 weeks

Treatment Details

Interventions

• Transcranial ExABlate

Trial Overview The study tests if using Transcranial MRI-Guided Focused Ultrasound (ExAblate) can safely disrupt the blood-brain barrier when combined with an ultrasound contrast agent. This could potentially allow more doxorubicin, a chemotherapy drug, to reach brain tumors.

Participant Groups

Group I: Transcranial ExAblate Experimental Treatment 1 Intervention

MR Guided Focused Ultrasound

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 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]

In a study of 123 patients undergoing magnetic resonance-guided focused ultrasound for tremor, those with lower skull density ratios were three times more likely to experience moderate or severe headaches, suggesting that tailored analgesic prophylaxis may be beneficial for these patients.

Women were found to have a significantly higher likelihood of experiencing nausea compared to men, with four times the odds, indicating a need for gender-specific considerations in managing side effects during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor. Cacho-Asenjo, E., Honorato-Cia, C., Nuñez-Cordoba, JM., et al.[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]

Transcranial microbubble-enhanced focused ultrasound (MB-FUS) safely and effectively opens the blood-brain barrier (BBB) in patients with infiltrating gliomas, as demonstrated in a Phase 0 clinical trial with MRI and histopathology confirming reproducible results.

The study found a significant increase in drug accumulation in treated tumor tissues, with a 2.2-fold increase in fluorescein compared to untreated areas, suggesting that MB-FUS could enhance the delivery of therapeutics for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. Anastasiadis, P., Gandhi, D., Guo, Y., et al.[2022]

Low-intensity MR-guided focused ultrasound combined with microbubbles shows promise for safely delivering drugs to the central nervous system by temporarily opening the blood-brain barrier, which is crucial for treating brain cancers.

Preclinical studies have demonstrated the safety and preliminary efficacy of this method in animal models, suggesting it could be a noninvasive and repeatable approach for targeting drug delivery in neuro-oncology patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. Meng, Y., Suppiah, S., Surendrakumar, S., et al.[2020]

Modern transcranial magnetic resonance-guided focused ultrasound is a non-invasive treatment that effectively targets and destroys specific areas of brain tissue, making it a promising option for various neurological disorders.

This technique uses real-time MR thermography to ensure safety by monitoring tissue temperatures, allowing for precise ablation without damaging surrounding brain structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency Ultrasound Ablation in Neurosurgery. Pomeraniec, J., Elias, WJ., Moosa, S.[2023]

High-intensity focused ultrasound (HIFU) is a promising non-invasive treatment option for various solid tumors, including those in the pancreas, liver, and prostate, showing potential as an alternative to traditional oncologic therapies.

HIFU can be combined with imaging techniques like MRI and ultrasound for real-time monitoring during treatment, enhancing its safety and efficacy while minimizing complications associated with open surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Introduction to High Intensity Focused Ultrasound: Systematic Review on Principles, Devices, and Clinical Applications. Izadifar, Z., Izadifar, Z., Chapman, D., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Surgical Management of Brain Tumors with Focused Ultrasound. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review. [2021]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in Focused Ultrasound for the Treatment of Brain Tumors. [2023]

5. France pubmed.ncbi.nlm.nih.gov

[Ultrasonic arrays: new therapeutic developments]. [2019]

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

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. [2020]

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

High-Frequency Ultrasound Ablation in Neurosurgery. [2023]

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

Emerging Therapeutic Strategies for Brain Tumors. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

An Introduction to High Intensity Focused Ultrasound: Systematic Review on Principles, Devices, and Clinical Applications. [2020]