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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating brain tumors using focused ultrasound guided by MRI. The goal is to safely open the blood-brain barrier, a protective shield around the brain, to help the cancer drug doxorubicin reach the tumor more effectively. The method uses Transcranial ExABlate, a focused ultrasound device. It is intended for individuals with brain tumors smaller than 2.5 cm who can attend study visits and communicate clearly during the procedure. The study aims to determine if this treatment is safe enough for further testing. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could lead to new treatment options for brain tumors.

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 prior data suggests that this technique is safe for brain tumor treatment?

Research has shown that MRI-guided focused ultrasound, such as the Transcranial ExAblate, is generally safe for opening the blood-brain barrier to treat brain tumors. Earlier studies tested this method on patients with brain tumors and found it to be well-tolerated.

Available studies report that side effects were minor and usually temporary. Common reactions included mild headaches and dizziness, but these did not last long. Importantly, no serious complications appeared in these initial trials. This suggests that the treatment is safe enough for further exploration in clinical trials. However, as this treatment is still under study, more data will help confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial ExAblate because it offers a non-invasive approach to treating brain tumors using MR Guided Focused Ultrasound. Unlike traditional methods like surgery or radiation, which can be invasive or affect surrounding healthy tissue, this technique targets and heats the tumor precisely without cutting into the skull. This unique delivery method minimizes damage to healthy brain tissue and reduces recovery time, potentially making it a safer and more efficient option for patients.

What evidence suggests that this technique is effective for brain tumors?

Research has shown that transcranial MRI-guided focused ultrasound, provided in this trial as Transcranial ExAblate, can target brain tumors through the skull. Studies have found that this method effectively heats tumor areas, visible through special MR temperature imaging. Early findings suggest that this technique can temporarily open the blood-brain barrier, potentially allowing more drugs to reach the tumor. Animal studies have demonstrated that this opening improves treatment results, making certain drugs more effective against brain tumors. These early results are promising for using focused ultrasound to treat brain tumors, but further research is needed to confirm its effectiveness in humans. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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

Able to communicate sensations during the ExAblate MRgFUS procedure.

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

I am mostly independent and can care for myself.

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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00147056

MRI-Guided Focused Ultrasound Feasibility Study for Brain ... The purpose of this study is to evaluate the safety of MRI-guided focused ultrasound thermal ablation of brain tumors performed through intact human skull using ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2939497/

Transcranial MRI-guided focused ultrasound surgery of brain ... We found that it was possible to focus an ultrasound beam transcranially into the brain and to visualize the heating with MR temperature imaging.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01304758

ExAblate Transcranial MR Guided Focused Ultrasound in ... The purpose of this study is to evaluate the safety and initial effectiveness of MRI-guided focused ultrasound thermal ablation of a designated ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4687492/

Transcranial MR-Guided Focused Ultrasound - PubMed Central Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model. Journal of ...

5. fusfoundation.org fusfoundation.org/for-researchers-and-clinicians/foundation-funded-research-projects/

Foundation Funded Research Projects Will FUS be safe and effective in treating patients with brain tumors? A Study to Evaluate the Safety and Feasibility of Transcranial MRI-Guided Focused ...

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

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The treatment effect of the ExAblate Neuro is achieved by guiding the focus of the ultrasound energy to the target region. The energy is then ...

7. dana-farber.org dana-farber.org/clinical-trials/13-016

A Study to Evaluate the Safety and Feasibility of ... The purpose of this study is to evaluate the safety of MRI-guided focused ultrasound thermal ablation of brain tumors performed through intact human skull ...