50 Participants Needed

Focused Ultrasound for Brain Cancer

(BRAINFUL Trial)

ML
CS
Overseen ByCan Sarica, MD
Age: 18+
Sex: Any
Trial Phase: Academic
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

Background: Accessing brain tumor material for pathological diagnosis requires invasive procedures that carry risk to patients including brain hemorrhages and death. Liquid biopsies are emerging non-invasive alternatives to direct tumour biopsies but the abundance of circulating tumor DNA (ctDNA) is relatively low and this limits our ability to accurately make the molecular diagnosis of brain tumors. 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 biopsies with high intensity focused ultrasound (HIFU) to enhance the release of tumor DNA into the circulation and increase the sensitivity/and specificity of liquid biopsies for brain tumors. The aim of this project is to build on our preliminary findings and investigate the the time dependent changes associated with HIFU of a tumor to see if it improves accuracy of diagnosis and specifically molecular subtyping of tumors based on peripheral blood and cerebrospinal fluid (CSF) circulating tumor derived markers following HIFU.

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 data supports the effectiveness of the treatment Magnetic Resonance Guided Focused Ultrasound for brain cancer?

Research shows that Magnetic Resonance Guided Focused Ultrasound (MRgFUS) is a promising noninvasive treatment that can precisely target and destroy brain tumors by focusing ultrasound energy, and it has been used successfully in treating other conditions like bone metastases and uterine fibroids. It also helps in delivering chemotherapy drugs more effectively to brain tumors by temporarily opening the blood-brain barrier.12345

Is focused ultrasound generally safe for use in humans?

Focused ultrasound, guided by MRI, is a noninvasive technique that has been used safely in humans for various conditions, including breast cancer and brain disorders. Studies have shown it can be used without opening the skull, and it has been tested in both animal models and human trials, demonstrating its safety and feasibility.12367

How is the treatment Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition different from other brain cancer treatments?

This treatment is unique because it uses focused ultrasound guided by MRI to noninvasively target and destroy brain tumors while also temporarily opening the blood-brain barrier, which can enhance the delivery of cancer drugs directly to the tumor site.12357

Research Team

GZ

Gelareh Zadeh, MD, PhD

Principal Investigator

University of Toronto

AM

Andres M. Lozano, MD, PhD

Principal Investigator

University of Toronto

Eligibility Criteria

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.
See 3 more

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
See 1 more

Timeline

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)

Treatment Details

Interventions

  • Magnetic Resonance Guided Focused Ultrasound Thalamotomy
  • Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Tumor cohortExperimental Treatment1 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 cohortExperimental Treatment1 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

Find a Clinic Near You

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+

Findings from Research

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.
Intracranial applications of magnetic resonance-guided focused ultrasound.Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]
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.
Focused Ultrasound Strategies for Brain Tumor Therapy.Bunevicius, A., McDannold, NJ., Golby, AJ.[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.
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]

References

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]
Focused Ultrasound Strategies for Brain Tumor Therapy. [2022]
Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain. [2023]
Noninvasive ablation of rabbit fetal and placental tissue targets in utero using magnetic resonance-guided high-intensity focused ultrasound. [2020]
Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy. [2006]
Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. [2022]
Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. [2020]