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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how focused ultrasound (FUS) can alter the environment around brain tumors. By using sound waves, researchers seek to understand the effects on the tumor and surrounding brain tissue. The trial uses a specific ultrasound machine, InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system, before planned surgery to gather crucial data. It suits individuals with a known or suspected brain tumor called glioma who are scheduled for surgery at Mayo Clinic. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment strategies.

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 prior data suggests that this focused ultrasound device is safe for brain tumor treatment?

Research has shown that focused ultrasound (FUS), using InSightec's ExAblate Neuro Model 4000 Type 2.0 system, received positive feedback in past studies. This device already has approval for other uses, such as treating essential tremor (a condition that causes shaking), indicating a level of safety. Studies have demonstrated that FUS can safely open the blood-brain barrier (a protective shield around the brain), enhancing the delivery of treatments to the brain.

No major safety concerns have been reported with its use. However, like any treatment, risks exist. Consulting a healthcare provider to understand potential side effects before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for brain tumors, such as surgery, chemotherapy, and radiation, which often involve invasive procedures and systemic effects, InSightec's ExAblate Neuro Model 4000 Type 2.0 offers a non-invasive approach using focused ultrasound technology. This treatment targets the tumor precisely with sound waves, potentially reducing damage to surrounding healthy tissue and minimizing side effects. Researchers are excited about this technique because it allows for targeted treatment with the potential for quicker recovery and fewer complications compared to traditional options.

What evidence suggests that this focused ultrasound device is effective for brain tumors?

Research has shown that focused ultrasound (FUS), which participants in this trial will receive using the InSightec's ExAblate Neuro Model 4000 Type 2.0 (220 KHz) system, can safely open the blood-brain barrier (BBB). This protective layer around the brain often prevents treatments from reaching brain tumors. Opening the BBB allows for more precise tumor targeting and improves drug delivery. Studies have demonstrated that FUS can create physical and heat effects using sound waves to impact brain tumors. These effects may alter the tumor environment, making it more responsive to treatments. Specifically, this method has been studied for glioblastoma, a type of brain tumor, with promising results in terms of safety and feasibility. Overall, these findings suggest that FUS could effectively improve treatment outcomes for brain tumors. ^{1 4 6 7 8}

Who Is on the Research Team?

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

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

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 am scheduled for brain surgery to remove a tumor.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

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

Focused ultrasound-mediated enhancement of blood– ... FUS is a promising strategy to safely disrupt the BBB, enabling precise and non-invasive lesion targeting, and enhance drug delivery.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2950329925000633

Regulation of the brain tumor microenvironment by focused ... From the perspective of the brain tumor microenvironment, FUS can produce mechanical and thermal effects by delivering sound waves to brain ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05317858

NCT05317858 | Blood-brain Barrier (BBB) Opening Using ... The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the ...

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038S037B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) Once targeting is complete, the treatment outcome is confirmed with adequate post-treatment MRI sequences. The Exablate Model 4000 Type 1.0 & ...

5. insightec.com insightec.com/news/bbb-study-exablate-neuro-glioblastoma/

Study of Exablate Neuro for BBB opening in Glioblastoma A study to evaluate the safety and feasibility of the Exablate Neuro for disrupting the blood brain barrier (BBB) in patients with Glioblastoma.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05733312

Extracellular Impact of Ultrasound-induced Blood-brain ... This study seeks to determine the impact of focused ultrasound (FUS) on the composition of the tumor extracellular microenvironment. ... InSightec's ExAblate ...

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

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The ExAblate Neuro is intended for use in the unilateral Thalamotomy treatment of idiopathic Essential Tremor patients with medication-refractory ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03551249

Study Details | NCT03551249 | Assessment of Safety and ... The ExAblate Model 4000 Type 2 system is intended for use as a tool to induce localized and temporary blood-brain barrier disruption in patients with ...