ExAblate 4000 System for Brain Tumor

Recruiting at 3 trial locations

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Human growth hormone, Valproate derivatives

Disqualifiers: Unstable cardiac status, Substance abuse, Renal impairment, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for benign (non-cancerous) brain tumors in children and young adults. The aim is to determine if the ExAblate 4000, a focused ultrasound device guided by MRI, is safe and practical for these tumors. It targets individuals with centrally located brain tumors requiring medical attention and without a high risk of bleeding. Participants should maintain consistent medication use and provide a detailed record of any seizures experienced. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of all condition-related medications for 30 days before joining. However, you must stop taking anticoagulants (blood thinners) one week before the procedure and valproate derivatives (seizure medications) two weeks before.

What prior data suggests that the ExAblate 4000 System is safe for treating benign intracranial tumors in children and young adults?

Research has shown that the ExAblate 4000 System is generally safe for treating brain conditions. Studies have found that side effects resemble those seen with thalamotomy, such as numbness or tingling in fingers and balance issues. These effects are common and manageable.

The system uses focused ultrasound, guided by MRI (a type of brain scan), to target and treat specific brain areas. Since this treatment is already used for other brain conditions, there is some confidence in its safety. However, as with any medical procedure, it is important to consider possible side effects and discuss them with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The ExAblate 4000 System is unique because it uses MR-Guided Focused Ultrasound to target brain tumors, offering a non-invasive alternative to traditional surgery and radiation. This system allows for precise targeting of tumor tissues, minimizing damage to surrounding healthy brain tissue. Researchers are excited about this technology because it may reduce recovery times and lessen side effects compared to conventional treatments like surgery and chemotherapy. Additionally, the non-invasive nature of the ExAblate 4000 System could make it a safer option for patients who are not ideal candidates for surgery.

What evidence suggests that the ExAblate 4000 System is effective for treating benign intracranial tumors?

Research shows that the ExAblate 4000 System, used in this trial, employs focused ultrasound to accurately target and treat brain tumors. This non-invasive method avoids surgery and uses MRI scans to direct ultrasound energy precisely. Studies have found that it can safely open the blood-brain barrier, a protective layer around the brain, enhancing tumor targeting and treatment. Early results suggest this system may effectively treat non-cancerous brain tumors in children and young adults. While researchers continue to collect more human data, the technology appears promising for improving the treatment of brain conditions. ^{1 5 6 7 8}

Who Is on the Research Team?

John Ragheb, MD

Principal Investigator

Miami Children's Research Institute - Nicklaus Children's Hospital

Are You a Good Fit for This Trial?

This study is for children and young adults with non-cancerous brain tumors that need treatment, can fit in an MRI machine, and have a head circumference of at least 52cm. They should be stable on current medications for their condition. Those with malignant tumors, unclear diagnosis without biopsy, or unable to undergo anesthesia are excluded.

Inclusion Criteria

Minimum head circumference will be 52cm

My medication doses have been stable for the last 30 days.

I have a non-cancerous brain tumor that needs treatment and is unlikely to bleed.

Exclusion Criteria

I cannot or do not want to have general anesthesia.

I am currently taking human growth hormone.

I have had thoughts of suicide or attempted suicide in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ExAblate 4000 treatment for benign intracranial tumors

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits as per study protocol

What Are the Treatments Tested in This Trial?

Interventions

• ExAblate 4000 System

Trial Overview The trial is testing the ExAblate 4000 System's safety and feasibility in treating benign brain tumors by using focused ultrasound waves to heat and destroy tumor tissue without invasive surgery.

How Is the Trial Designed?

Group I: ExAblate 4000 System 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

Cintredekin besudotox (CB) delivered via convection-enhanced delivery (CED) showed a favorable risk-benefit profile in treating recurrent glioblastoma multiforme (GBM), with a median survival of 42.7 weeks for GBM patients and 55.6 weeks for those with optimally positioned catheters.

The study involved 51 patients, with 46 having GBM, and found that the maximum tolerated concentration of CB was 0.5 microg/mL, leading to tumor necrosis, while infusion durations of up to 6 days were well tolerated, highlighting the importance of catheter placement for effective drug distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group. Kunwar, S., Prados, MD., Chang, SM., et al.[2022]

Malignant brain tumors remain difficult to treat, with long-term survival only improving from 6 to 15 months over the last 80 years, despite advancements in surgery, chemotherapy, and radiotherapy.

Immunotherapy, particularly using immune modulators like CTLA-4 and PD-1/PD-L1, is being actively researched in ongoing phase I and III trials, showing promise in targeting glioma antigens, but challenges remain in achieving complete responses and understanding the lack of adverse brain inflammation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of EGFRvIII as the target for glioma vaccines. Lowenstein, PR., Castro, MG.[2021]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01698437

Magnetic Resonance (MR) Guided Focused Ultrasound in ... Transcranial MR-Guided Focused Ultrasound for Brain Tumors, Intervention/Treatment, Device : Non-invasive intervention with focused ultrasound (ExAblate 4000).

3. 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.

4. tandfonline.com tandfonline.com/doi/abs/10.1080/17434440.2021.1921572

Device profile of exAblate Neuro 4000, the leading system ... The leading system for brain Magnetic Resonance Guided Focused Ultrasound technology; an overview of its safety and efficacy in the treatment of medically ...

5. abta.org abta.org/mindmatters/scientific_advances/sonala-001/

A Dose Escalation and Expansion Study of Sonodynamic ... The goals of this study are to evaluate the safety, preliminary efficacy (progression free survival), Dose-Limiting Toxicities (DLTs), ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038S006B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) Adverse events for the Exablate Neuro are consistent with those generally reported for thalamotomy, including numbness/tingling of the fingers, imbalance/ ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03028246

NCT03028246 | A Feasibility Safety Study of Benign ... The purpose of this study is to evaluate the safety and feasibility of managing benign brain tumor size using ExAblate 4000 treatment.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04526262

Study Details | NCT04526262 | Assessment of Initial ... The proposed study is to evaluate initial efficacy and safety of the BBB disruption with transcranial MRI-guided focused ultrasound (ExAblate 4000 type 2.0) in ...