Sonodynamic Therapy for Glioblastoma

(GBM 001 Trial)

Overseen by Shayan Moosa, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Shayan Moosa, MD

Must not be taking: Phototoxic substances, Antioxidants

Disqualifiers: Pregnancy, Cardiac disease, Infections, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This pilot study will evaluate the safety and feasibility of combining an investigational drug called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients who have 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 approach is called sonodynamic therapy (SDT), and this investigational therapy is being tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for recurrent GBM.

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 data supports the effectiveness of the treatment Sonodynamic Therapy for Glioblastoma?

Research shows that Sonodynamic Therapy (SDT) using 5-Aminolevulinic Acid (5-ALA) and focused ultrasound has been effective in treating malignant gliomas and other cancers like melanoma. The treatment works by using ultrasound to activate a special substance (5-ALA) that targets tumor cells, potentially offering a non-invasive way to treat deeply located brain tumors. ^{1 2 3 4 5}

Is sonodynamic therapy safe for humans?

There is currently no clinical data on the safety of sonodynamic therapy for malignant gliomas, but preclinical studies suggest it is relatively non-invasive and can be applied repeatedly. ^{1 2 3 4 5}

How is sonodynamic therapy different from other treatments for glioblastoma?

Sonodynamic therapy (SDT) for glioblastoma is unique because it uses a combination of a chemical called 5-aminolevulinic acid (5-ALA) and focused ultrasound to target and kill tumor cells. Unlike traditional treatments like surgery, radiation, and chemotherapy, SDT is non-invasive and can be repeated, using ultrasound to penetrate deep into the brain to reach tumors. ^{1 2 4 6 7}

Research Team

Shayan Moosa, MD

Principal Investigator

UVA

Eligibility Criteria

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 am between 18 and 80 years old.

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

Trial Timeline

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

Treatment Details

Interventions

• Sonodynamic Therapy (Other)

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.

Participant Groups

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

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

Who Is Running the Clinical Trial?

Shayan Moosa, MD

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

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]

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]

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]

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]

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) 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Investigation of the tumoricidal effects of sonodynamic therapy in malignant glioblastoma brain tumors. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Sonodynamic Therapy for Gliomas. Perspectives and Prospects of Selective Sonosensitization of Glioma Cells. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic acid-mediated sonodynamic therapy induces anti-tumor effects in malignant melanoma via p53-miR-34a-Sirt1 axis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Sonodynamic therapy for gliomas. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Fluorescein-mediated sonodynamic therapy in a rat glioma model. [2022]