Sonodynamic Therapy for Glioblastoma

(GBM 001 Trial)

Overseen By Zachary Sturgill

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Shayan Moosa, MD

Must not be taking: Phototoxic substances, Antioxidants

Disqualifiers: Pregnancy, Cardiac disease, Infections, 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: 1

Duration: 1-3 weeks

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for glioblastoma, a type of brain cancer that often recurs after treatment. Researchers are testing the safety and feasibility of combining a drug called 5-ALA with focused ultrasound, a non-invasive technique, to target and damage cancer cells before surgery. This approach, known as Sonodynamic Therapy, is intended for individuals whose glioblastoma has returned and who have tumors in surgically accessible areas of the brain. Participants should have a measurable tumor and be prepared for surgery to remove it. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use certain phototoxic substances, anticoagulants, or supplements with antioxidant effects. It's best to discuss your current medications with the trial team.

What prior data suggests that this sonodynamic therapy is safe for glioblastoma patients?

Research shows that sonodynamic therapy, which combines the drug 5-ALA with focused ultrasound, is being tested for safety in treating glioblastoma, a type of brain tumor. Earlier studies have generally found 5-ALA to be well-tolerated, with some patients experiencing mild side effects like nausea and sensitivity to light. Focused ultrasound, another component of this treatment, is non-invasive and aims to target tumor cells without harming normal brain tissue.

Although limited data exists on using these together in humans for this specific condition, the Phase 1 trial primarily assesses safety and tolerability. While much remains to be learned, the components of sonodynamic therapy have shown promise in being safe in other contexts. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sonodynamic Therapy is unique because it combines a special drug called 5-ALA with low-intensity focused ultrasound (LIFU) to treat glioblastoma. Unlike standard treatments like surgery, radiation, and chemotherapy, this therapy aims to target and destroy cancer cells more precisely without harming surrounding healthy tissue. Researchers are excited about its potential to enhance treatment effectiveness while minimizing side effects, offering a promising new approach for tackling this aggressive brain cancer.

What evidence suggests that sonodynamic therapy might be an effective treatment for glioblastoma?

Research has shown that sonodynamic therapy (SDT), which participants in this trial will receive, might help treat glioblastoma (GBM), a type of brain cancer. When 5-aminolevulinic acid (5-ALA) combines with focused ultrasound (FUS), studies have found it can effectively attack tumor cells while protecting healthy tissue. In some preclinical studies, SDT even completely cleared tumors. These results suggest that SDT could be a promising new option for managing recurrent GBM. ^{3 6 7 8 9}

Who Is on the Research Team?

Shayan Moosa, MD

Principal Investigator

UVA

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with recurrent glioblastoma, a type of brain tumor. Participants must have a specific size and location of the tumor that's accessible for surgery, no recent strokes or severe heart conditions, and be able to swallow pills. They should not be pregnant, have metal in their body that interferes with ultrasound, or have taken certain treatments recently.

Inclusion Criteria

Recurrence will be assessed by imaging and confirmed by consensus at tumor board

My tumor is between 6 and 20 cm3 in size and shows up on contrast imaging.

I can safely undergo another brain surgery.

Exclusion Criteria

You are allergic or sensitive to 5-ALA.

You are allergic to porphyrins.

Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of sonodynamic therapy (SDT) with 5-ALA and LIFU occurs 1-3 weeks prior to GBM resection

1-3 weeks

1 visit (in-person, overnight stay)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging and adverse event assessment

Up to 100 days

What Are the Treatments Tested in This Trial?

Interventions

• Sonodynamic Therapy

Trial Overview The study tests sonodynamic therapy (SDT) using an investigational drug called 5-ALA combined with low-intensity focused ultrasound on patients before surgery. SDT aims to non-invasively target and damage tumor cells while sparing normal tissue.

How Is the Trial Designed?

Group I: Sonodynamic Therapy (5-ALA + LIFU) Experimental Treatment 1 Intervention

Administration of SDT occurs 1-3 weeks prior to GBM resection

Sonodynamic Therapy is already approved in United States, European Union for the following indications:

Approved in United States as 5-Aminolevulinic Acid (5-ALA) for:

• Fluorescence-assisted resection of gliomas

Approved in European Union as 5-Aminolevulinic Acid (5-ALA) for:

• Fluorescence-assisted resection of gliomas

Who Is Running the Clinical Trial?

Shayan Moosa, MD

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

The combination of 220-kHz transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) and 5-aminolevulinic acid (5-ALA) effectively reduced cell viability and induced apoptosis in malignant glioma cells, demonstrating significant anti-tumor effects in both in vitro and in vivo studies.

This treatment approach minimized damage to normal brain tissue, suggesting that sonodynamic therapy (SDT) with TcMRgFUS and 5-ALA is a safe and promising option for treating malignant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid. Yoshida, M., Kobayashi, H., Terasaka, S., et al.[2023]

Sonodynamic therapy (SDT) shows promise as a treatment for gliomas, utilizing non-toxic sonosensitizers activated by low-frequency ultrasound to induce cell death through mechanisms like reactive oxygen species generation and cell membrane destabilization.

Pre-clinical studies in glioma cell cultures and animal models indicate that SDT can effectively control tumors and improve survival without damaging surrounding brain tissue, although clinical trials in humans are still in the early stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonodynamic therapy for gliomas. Bunevicius, A., Pikis, S., Padilla, F., et al.[2022]

5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) effectively inhibited tumor growth and increased apoptosis in malignant melanoma in vivo, as demonstrated in tumor transplantation experiments with BALB/c nude mice.

The therapy works by enhancing the expression of miR-34a, which activates the p53 pathway and creates a positive feedback loop that promotes anti-tumor effects, indicating a novel mechanism of action for treating this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid-mediated sonodynamic therapy induces anti-tumor effects in malignant melanoma via p53-miR-34a-Sirt1 axis. Hu, Z., Fan, H., Lv, G., et al.[2022]

Sonodynamic therapy (SDT) using fluorescein and low-intensity focused ultrasound effectively inhibited the growth of ectopic gliomas in rats, demonstrating its potential as a cancer treatment.

The treatment showed tumor-specific accumulation of fluorescein, indicating that it could selectively target gliomas, particularly in areas where the blood-brain barrier is compromised.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescein-mediated sonodynamic therapy in a rat glioma model. Prada, F., Sheybani, N., Franzini, A., et al.[2022]

Sonodynamic therapy (SDT) using 5-Aminolevulinic acid (5-ALA) and focused ultrasound (FUS) significantly increased glioblastoma cell death compared to using 5-ALA or FUS alone, with a 47% reduction in cell viability for C6 cells.

The study demonstrated that SDT led to a substantial increase in apoptotic markers, indicating a strong mechanism of action for inducing cell death in glioblastoma, suggesting a promising new treatment approach for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the tumoricidal effects of sonodynamic therapy in malignant glioblastoma brain tumors. Sheehan, K., Sheehan, D., Sulaiman, M., et al.[2021]

5-aminolevulinic acid (5-ALA)-based sonodynamic therapy (SDT) significantly enhances the cytotoxic effects of bleomycin (BLM) on mouse mammary tumor cells, achieving nearly complete cell death (0.09% viability) at 1 MHz and higher power settings, compared to much higher viability in the SDT-only group.

In vivo studies confirmed that the combination of 5-ALA-based SDT and BLM was more effective than either treatment alone, suggesting that this approach not only kills tumor cells directly but may also induce vascular shutdown, contributing to tumor shrinkage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin. Osaki, T., Ono, M., Uto, Y., et al.[2017]

Sonodynamic therapy (SDT) using tumor-seeking sonosensitizers like 5-aminolevulinic acid shows promise for controlling recurring gliomas, potentially offering a non-invasive treatment option that can penetrate deep brain tissues.

While current treatments for gliomas only modestly improve survival, SDT could provide a new approach with the ability for repeated applications, although clinical data on its efficacy and safety are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonodynamic Therapy for Gliomas. Perspectives and Prospects of Selective Sonosensitization of Glioma Cells. Bilmin, K., Kujawska, T., Grieb, P.[2020]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10813104

Project Details - NIH RePORTER Sonodynamic therapy using MRI-guided focused ultrasound in combination with 5-aminolevulinic acid to treat recurrent glioblastoma multiforme. Project Number ...

2. nature.com nature.com/articles/s41598-025-85314-6

Repeated 5-aminolevulinic acid mediated sonodynamic ... Repeated SDT using transcranial-focused ultrasound together with 5-ALA can optimize anti-tumour effects and even lead to complete clearance of the tumours.

3. fusfoundation.org fusfoundation.org/posts/preclinical-studies-advance-focused-ultrasound-for-glioblastoma-parkinsons-disease/

Preclinical Studies Advance Focused Ultrasound for ... Research led by Kullervo Hynynen, PhD, showed sonodynamic therapy produced significant anti-tumor effects and increased survivability in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06039709

Sonodynamic Therapy in Patients With Recurrent GBM Focused ultrasound (FUS) can be used to non-invasively destroy tumor tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial ...

5. thejns.org thejns.org/focus/view/journals/neurosurg-focus/57/3/article-pE7.xml

A review of sonodynamic therapy for brain tumors in In preclinical models of high-grade glioma and GBM, SDT has shown evidence of targeted tumor cell death via the production of reactive oxygen species. Emerging ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06665724

Study Details | NCT06665724 | Clinical Trial Evaluating ... This trial is designed to evaluate safety and explore possible efficacy of 5-aminolevulinic acid hydrochloride (5-ALA HCl, Gliolan®) with CV01 delivery of ...

7. fusfoundation.org fusfoundation.org/posts/first-participant-receives-sonodynamic-therapy-for-glioblastoma-in-new-clinical-trial/

First Participant Receives Sonodynamic Therapy for ... A new clinical trial is investigating sonodynamic therapy for patients with recurrent glioblastoma.

8. mdpi.com mdpi.com/2075-1729/15/5/718

Sonodynamic Therapy Using 5-Aminolevulinic Acid for ... This review provides an insight into the use of focused and diffuse ultrasound in the treatment of GBM using 5-ALA-SDT, its mechanism of action and immune ...

9. nature.com nature.com/articles/s41598-019-46832-2

MR-guided Focused Ultrasound Facilitates Sonodynamic ... Transcranial MRI-guided focused ultrasound (MRgFUS) and real-time MRI thermometry were used to monitor the therapy in a rat brain tumor model.