Focused Ultrasound for Brain Cancer

Overseen By Maheleth Llinas

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: Temozolomide

Must not be taking: Bevacizumab, Anticoagulants

Disqualifiers: Cardiac disease, Severe hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: 14

Duration: 6-8 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to treat brain cancer, specifically glioblastoma, by using focused ultrasound to temporarily open the blood-brain barrier. The goal is to determine if this approach, known as Focused Ultrasound Blood-Brain Barrier Disruption, is safe and feasible for individuals already receiving the standard chemotherapy treatment, temozolomide. Participants will undergo focused ultrasound sessions and imaging tests to assess the treatment's effectiveness. Individuals who have undergone glioblastoma surgery, are in the maintenance phase of their treatment, and have a clearly defined tumor on an MRI scan may be suitable candidates for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on certain treatments like bevacizumab or anti-coagulants close to the treatment time. It's best to discuss your specific medications with the trial team.

What prior data suggests that this focused ultrasound technique is safe for brain cancer patients?

Research has shown that focused ultrasound (FUS) is a promising method to safely open the blood-brain barrier (BBB). This technique allows precise targeting of brain areas and enhances drug delivery to the brain. Studies have demonstrated that FUS can temporarily open the BBB, increasing treatment effectiveness.

FUS is considered safe because it is non-invasive and aids in delivering chemotherapy to brain tumors like glioblastoma. This method has been used for other conditions and is generally well-tolerated with few side effects. Early studies also suggest that low-intensity ultrasound can increase drug levels in the brain without major safety concerns.

Although this treatment remains in early testing, current evidence suggests it is a safe option for patients, especially when combined with standard chemotherapy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatment for brain cancer, which typically relies on chemotherapy drugs like temozolomide (TMZ) alone, focused ultrasound blood-brain barrier (BBB) disruption offers a unique approach. This treatment uses the Next Generation Dome Helmet to send ultrasound waves that temporarily open the BBB, allowing better delivery of chemotherapy directly to the brain tumor. Researchers are excited about this technique because it enhances the effectiveness of existing drugs by improving their access to the tumor site, potentially increasing treatment efficacy and minimizing side effects.

What evidence suggests that focused ultrasound is effective for brain cancer?

Research shows that focused ultrasound (FUS) offers a promising way to safely open the blood-brain barrier (BBB). The BBB acts as a natural shield, preventing many treatments from reaching the brain. In this trial, participants will undergo FUS-mediated BBB disruption using the Next Generation Dome Helmet during the maintenance phase of standard-of-care temozolomide (TMZ) chemotherapy. Studies have found that FUS can help drugs reach brain tumors like glioblastoma by making the BBB more permeable. This non-invasive method, which doesn't require surgery, has been linked to improved delivery of chemotherapy drugs. Early evidence suggests that this technique could enhance the effectiveness of brain cancer treatments, potentially leading to better survival rates. ^{1 2 3 4 6}

Who Is on the Research Team?

Nir Lipsman

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for adults with high-grade glioma, specifically glioblastoma, who are in the maintenance phase of standard chemotherapy. Participants must be able to undergo multiple focused ultrasound treatments and MRI scans, provide blood samples, and have their health monitored over time.

Inclusion Criteria

I am between 18 and 85 years old.

My diagnosis is Glioblastoma according to the latest standards.

I've had surgery, radiation, and TMZ for my cancer without issues and am ready for more TMZ.

Exclusion Criteria

I have a long-term lung condition.

I experience symptoms like headaches, nausea, or dizziness that could indicate high brain pressure.

I need more corticosteroids than before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo repeated FUS BBB disruption treatments during the maintenance phase of temozolomide chemotherapy, with MRI guidance and biomarker analysis.

6-8 months

Up to 6 cycles spaced 4-6 weeks apart

Follow-up

Participants are monitored for progression-free survival and overall survival during routine neuro-oncology visits.

Until end of life

Every 8 weeks during the first year, every 12 weeks during the second year

What Are the Treatments Tested in This Trial?

Interventions

• Focused Ultrasound Blood-Brain Barrier Disruption

Trial Overview The study tests a new method using focused ultrasound (FUS) with a Next Generation Dome Helmet to temporarily open the brain's protective barrier during chemotherapy. This aims to improve treatment effectiveness by allowing better drug delivery.

How Is the Trial Designed?

Group I: Focused Ultrasound BBB Disruption Using the Next Generation Dome Helmet and Definity Experimental Treatment 2 Interventions

Participants in this single-arm study will undergo repeated sessions (up to 6 cycles spaced 4-6 weeks apart) of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) disruption using the Next Generation Dome Helmet (NGDH) during the maintenance phase of standard-of-care temozolomide (TMZ) chemotherapy. At the time of each FUS session, participants will receive their prescribed standard of care TMZ dose, as well as an intravenous injection of DEFINITY® ultrasound contrast agent that enables targeted BBB opening. Each session will be guided by MRI, and imaging will be used to assess the extent of BBB disruption. Clinical and safety assessments, blood sampling for biomarker analysis, and follow-up imaging will be conducted throughout the study period.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

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. clinicaltrials.gov clinicaltrials.gov/study/NCT07179328

NCT07179328 | Focused Ultrasound Blood-Brain Barrier ... The goal of this clinical trial is to evaluate the safety and feasibility of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) ...

3. fusfoundation.org fusfoundation.org/diseases-and-conditions/glioblastoma/

Glioblastoma Focused ultrasound is a noninvasive therapy that is transforming the treatment and quality of life for patients with glioblastoma.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586824003254

Focused ultrasound blood-brain barrier disruption in high ... FUS is a safe and effective tool for blood–brain barrier disruption. FUS result in enhanced delivery of chemotherapeutic with near significant survival ...

5. nyp.org nyp.org/advances/article/disrupting-the-blood-brain-barrier-to-improve-glioblastoma-treatment

Disrupting the Blood-Brain Barrier to Improve Glioblastoma ... With sonication, we are using focused ultrasound to break through the BBB to increase drug delivery to the area of the brain where the ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/25/13/3793/81967/Safety-and-Feasibility-of-Repeated-and-Transient

Safety and Feasibility of Repeated and Transient Blood–Brain ... Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations. Patients ...