Focused Ultrasound for Brain Cancer

(BRAINFUL Trial)

Overseen By Can Sarica, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Hydrocephalus, Cardiac disease, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 27

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to diagnose brain tumors without invasive surgery. It combines a non-invasive technique called focused ultrasound (specifically, Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition) with blood tests to determine if it can detect tumor DNA more accurately. The trial includes two groups: one with brain tumors undergoing this new treatment and another with essential tremor unrelated to tumors, to compare DNA changes. Ideal candidates have newly diagnosed brain lesions that can be surgically biopsied and can undergo MRI scans without significant discomfort. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research in non-invasive tumor diagnosis.

Will I have to stop taking my current medications?

If you are taking medications that increase bleeding risk, such as aspirin, antiplatelet medications, or anticoagulants, you will need to stop them for a specific period before treatment. For example, aspirin should be stopped 7 days prior, and certain anticoagulants should be stopped 48 to 72 hours before treatment.

What prior data suggests that this method is safe for brain cancer patients?

Studies have shown that Magnetic Resonance Guided Focused Ultrasound (MRgFUS) offers a promising way to treat brain tumors. Research indicates that MRgFUS can safely target and heat specific brain areas to treat tumors without surgery, reducing risks compared to traditional invasive brain surgery.

In trials, patients have generally tolerated MRgFUS well. Some reported mild side effects, such as headaches or dizziness, but serious complications were rare. Safety data from these studies provide a cautiously optimistic view of MRgFUS as a non-invasive option for treating brain tumors.

Additionally, MRgFUS has already received approval for treating other conditions like essential tremor, a disorder that causes rhythmic shaking. This approval suggests the treatment's safety for other uses, which may reassure those considering this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for brain cancer because it offers a non-invasive way to target tumors with precision. Unlike traditional surgery or radiation, MRgFUS uses ultrasound waves guided by MRI to ablate, or destroy, tumor tissues without needing to cut into the brain. This method reduces recovery time and minimizes damage to surrounding healthy tissue. Additionally, combining MRgFUS with liquid biopsy acquisition allows for real-time monitoring of tumor DNA in the blood, offering new insights into treatment effectiveness and tumor behavior.

What evidence suggests that Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition is effective for brain cancer?

Research has shown that high-intensity focused ultrasound (HIFU) can effectively target brain tumors without harming healthy tissue. In this trial, participants in the tumor cohort will undergo partial tumor ablation using Magnetic Resonance Guided Focused Ultrasound (MRgFUS), a form of HIFU. Studies have found that HIFU can reach soft tissue and make changes at the tumor site, aiding in tumor treatment. Early results suggest that combining HIFU with liquid biopsies—a blood test that detects cancer cells—might improve the accuracy of brain tumor diagnosis. This could lead to better identification of tumor types and more personalized treatment. Overall, using HIFU in brain cancer treatment shows promise for making diagnosis and treatment more precise and less invasive. ^{1 2 3 4 6}

Who Is on the Research Team?

Gelareh Zadeh, MD, PhD

Principal Investigator

University of Toronto

Andres M. Lozano, MD, PhD

Principal Investigator

University of Toronto

Are You a Good Fit for This Trial?

Adults over 18 with new MRI-diagnosed brain tumors suitable for biopsy can join this trial. They must be able to give consent, handle lying down in an MRI without severe claustrophobia, and accept surgery post-treatment. A good performance status (Karnofsky rating 70-100) is required.

Inclusion Criteria

I can communicate during the MRgFUS procedure.

I can sign consent, follow study rules, lie flat for MRI without severe claustrophobia, and agree to surgery after HIFU.

I am mostly able to care for myself and carry out normal activities.

Exclusion Criteria

MRI findings: Active infection/inflammation, Acute or chronic brain haemorrhages, Moderate/severe brain edema or midline shift >15 mm, Clips or other metallic implanted objects in the skull or the brain, except shunts, Significant cardiac disease or unstable hemodynamic status, On medications that increase the bleeding risk, specifically: a) aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abciximab) for the last 7 days prior to treatment; b) oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours, and intravenous or subcutaneous heparin-derived compounds for the last 48 hours, Abnormal coagulation profile, specifically: platelet <100,000/μl, Prothrombin Time >14 seconds, activated partial thromboplastin time (aPTT) >36 seconds, and INR > 1.3, Unqualified fit for the anaesthesia by an anesthesiologist assessment, ASA IV-V, Currently in a clinical trial involving an investigational product or non-approved use of a drug or device, Pregnant and lactating women

My treatment area is near the skull's inner layer or base.

Unable to complete high-density CT and MRI studies of the head at the any other MRI contraindication, such as: Large body habitus and not fitting comfortably into the scanner, Difficulty lying supine and still for up to 2 in the MRI unit or significant claustrophobia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRgFUS Procedure

Participants undergo MRgFUS to enhance the release of tumor DNA into circulation

1 day

1 visit (in-person)

Post-MRgFUS Monitoring

Blood and CSF samples are collected at several timepoints to measure cfDNA levels

1 day

Multiple timepoints within 24 hours

Surgery and Post-Surgery Monitoring

Standard of care tumor biopsy/excision followed by blood sample collection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Magnetic Resonance Guided Focused Ultrasound Thalamotomy
• Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition

Trial Overview The BRAINFUL trial tests if using high-intensity focused ultrasound (HIFU) alongside liquid biopsies improves the accuracy of diagnosing brain tumors by enhancing tumor DNA release into blood/CSF.

How Is the Trial Designed?

Group I: Tumor cohort Experimental Treatment 1 Intervention

Intervention 1: Participants will undergo a partial tumor ablation with MRgFUS using ExAblate Neuro 4000 device (InSightec Ltd, Tirat Carmel, Israel). Blood and CSF samples will be drawn on several timepoints before and after the procedure. Intervention 2: Participants will undergo a standard of care tumor biopsy/excision one day after the "Intervention 1". Blood samples will be drawn on several timepoints before and after the procedure.

Group II: Essential tremor cohort Experimental Treatment 1 Intervention

To identify the levels of circulating free DNA release after MRgFUS procedure in non-tumoral patients and to check whether the MRgFUS procedure induce tumoral mutations itself, we will draw blood samples from essential tremor patients before and after standard of care MRgFUS thalamotomy procedure.

Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Exablate Model 4000 Type 2.0/2.1 for:

• Glioblastoma brain tumors

Approved in European Union as Insightec’s focused ultrasound platform for:

• Glioblastoma brain tumors

Approved in Canada as Exablate Model 4000 Type 2.0/2.1 for:

• Glioblastoma brain tumors

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Brain Canada

Collaborator

Trials

22

Recruited

6,100+

Published Research Related to This Trial

In a study involving 30 women with breast cancer, MRgFUS treatment resulted in an impressive average of 96.9% tumor necrosis, indicating its high effectiveness in ablating breast carcinomas.

The procedure was well tolerated with minimal adverse effects, especially when performed under local anesthesia, suggesting it could be a safe noninvasive alternative to traditional surgical methods like lumpectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. Furusawa, H., Namba, K., Thomsen, S., et al.[2022]

A novel method using craniectomy and a high-frequency transducer significantly improved the accuracy of targeting small brain structures in rodents, achieving a 133% increase in precision compared to previous methods.

This approach allows for effective noninvasive lesioning of deep brain areas, which is crucial for studying neurological disorders in chronic disease models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain. Cornelssen, C., Payne, A., Parker, D., et al.[2023]

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]

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]

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) effectively targets and thermally treats specific fetal organs in a rabbit model, achieving high temperatures necessary for tissue necrosis.

The use of proton resonance frequency shift (PRFS) thermometry allows for precise temperature monitoring during treatment, suggesting that MRgHIFU could be a safer, noninvasive alternative to traditional surgical methods for addressing fetal organ anomalies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive ablation of rabbit fetal and placental tissue targets in utero using magnetic resonance-guided high-intensity focused ultrasound. Piorkowska, K., Waspe, AC., Wang, T., 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]

MRI-guided high-intensity focused ultrasound (MRIgFUS) shows promise as an effective method for thermocoagulating recurrent glioblastoma multiforme, as demonstrated in a Phase I study involving three patients.

While MRIgFUS can successfully destroy tumor tissue, there is a risk of neurological deficits due to unintended heating of surrounding brain tissue, prompting the development of software modifications to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy. Ram, Z., Cohen, ZR., Harnof, S., et al.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5907801/

Magnetic resonance–guided interstitial high-intensity ... In the present article, we propose a system that utilizes an intraparenchymal catheter to deliver HIFU therapy to treat intracranial neoplasms, and we describe ...

2. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rycan.230074

High-Intensity Focused Ultrasound Surgery for Tumor ... This review presents the latest HIFU applications, from investigational to clinically approved, in the field of tumor ablation.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04940507

Study Details | NCT04940507 | BRAINFUL (BRAIN Tumor ... We have recently shown promising results that suggest that the analysis of blood samples can distinguish brain tumor types. We now want to couple liquid ...

4. 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 ...

5. jtultrasound.biomedcentral.com jtultrasound.biomedcentral.com/articles/10.1186/2050-5736-2-17

First noninvasive thermal ablation of a brain tumor with MR ... High-intensity focused ultrasound (HIFU) can penetrate soft tissue to producephysiological effects at the target while sparing healthy tissue.

6. fusfoundation.org fusfoundation.org/diseases-and-conditions/brain-tumors/

Brain Tumors Learn about clinical trials that are investigating the use of focused ultrasound to treat Brain Tumors.