Focused Ultrasound for Brain Tumor

Overseen By Neurologic Surgery Research Team

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: 5-ALA

Disqualifiers: Cardiac disease, Coagulative disease, Seizure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses Focused Ultrasound to target brain tumors in patients with large gliomas. The treatment aims to open up the tumor area, making it easier to deliver and assess drugs. Researchers hope this will improve understanding and treatment of these tumors. Focused Ultrasound (FUS) is a non-invasive technique that uses converging ultrasound waves to temporarily open the blood-brain barrier, enhancing drug delivery to brain tumors.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that routine drugs administered before and during surgery will be evaluated, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system for brain tumors?

Focused Ultrasound (FUS) is a non-invasive treatment that has shown promise in safely and temporarily disrupting the blood-brain barrier, which can help deliver therapies to brain tumors. It has been studied in combination with other treatments for brain conditions, showing potential for improving treatment delivery and effectiveness. ^{1 2 3 4 5}

Is focused ultrasound for brain tumors safe for humans?

Focused ultrasound has been tested in animals and non-human primates, showing it can open the blood-brain barrier without causing significant harm like edema (swelling) or hemorrhage (bleeding). This suggests it may be safe for humans, but more research is needed to confirm this. ^{1 4 6 7 8}

How does the treatment ExAblate Neuro Model 4000 differ from other treatments for brain tumors?

The ExAblate Neuro Model 4000 uses focused ultrasound, a noninvasive technique that can safely and temporarily open the blood-brain barrier, allowing treatments to reach brain tumors more effectively. This system is unique because it combines MRI guidance with high-intensity focused ultrasound to target and treat brain tumors without surgery. ^{1 4 5 9 10}

Research Team

Terence C. Burns, M.D., Ph.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with a suspected or diagnosed diffuse glioma brain tumor, large enough (≥3cm) to be partially targeted by focused ultrasound but small enough for standard surgery. Participants must be able to undergo surgery in Rochester, MN and have an ECOG performance status of 0-2. Pregnant women, prisoners, those mentally handicapped, or anyone with certain cardiac diseases or blood-borne infections are excluded.

Inclusion Criteria

I am scheduled for brain surgery to remove a tumor.

Provide written informed consent for the current study and the Neuro-Oncology biorepository for archiving of microdialysate and blood samples collected on this protocol

I have a brain tumor that is the right size for focused ultrasound but can still be partially removed surgically.

Exclusion Criteria

I have seizures not caused by my tumor, or a drug/alcohol problem, not controlled by medication.

Patients who are not appropriate surgical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings

Vulnerable populations: pregnant or nursing women, prisoners, mentally handicapped

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Preparation

Participants undergo pre-operative imaging and preparation for focused ultrasound treatment

1 week

1 visit (in-person)

Intraoperative Treatment

Focused ultrasound is performed immediately prior to clinically indicated brain tumor resection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse events and collection of microdialysate aliquots post-surgery

3 months

Treatment Details

Interventions

• InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system

Trial Overview The study tests the effect of focused ultrasound on brain tumors using InSightec's ExAblate Neuro Model system. It aims to understand how this technique alters the tumor microenvironment by comparing regions treated with FUS against untreated ones through microdialysis catheters.

Participant Groups

Group I: Focused Ultrasound Experimental Treatment 1 Intervention

Subjects with known or suspected glioma (≥3cm) undergoing routine planned neurosurgical resection will undergo a focused ultrasound prior to the surgery with the InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system

InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system is already approved in United States, European Union for the following indications:

Approved in United States as ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system for:

• Essential tremor
• Parkinson's disease
• Neuropathic pain

Approved in European Union as ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system for:

• Essential tremor
• Parkinson's disease
• Neuropathic pain

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

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]

References

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

Preliminary study on Low Intensity Focused Ultrasound system For neuromodulation. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Ex vivo optimisation of a heterogeneous speed of sound model of the human skull for non-invasive transcranial focused ultrasound at 1 MHz. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Quantitative analysis of in-vivo microbubble distribution in the human brain. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Differential evolution method to find optimal location of a single-element transducer for transcranial focused ultrasound therapy. [2022]

5. 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]

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

Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers. [2016]

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

A Clinical System for Non-invasive Blood-Brain Barrier Opening Using a Neuronavigation-Guided Single-Element Focused Ultrasound Transducer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping. [2019]

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

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

10. Scotland pubmed.ncbi.nlm.nih.gov

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