Sonodynamic Therapy for Brain Cancer

Overseen By Phase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Must not be taking: Phototoxic substances

Disqualifiers: Infections, Stroke, Cardiac issues, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to explore a new treatment for recurrent brain cancer using sonodynamic therapy, which combines sound waves with a special drug called ALA (Aminolevulinic acid HCl). Researchers seek to determine the safety and effectiveness of this treatment when used with a focused ultrasound device (MR-Guided Focused Ultrasound device, MRgFUS). The trial includes multiple groups testing different doses and timing to identify the best approach. It seeks participants with high-grade gliomas who have undergone surgery and whose cancer has returned after standard treatments. As an Early Phase 1 trial, this 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 need to stop taking your current medications. However, there is a required 14-day period without chemotherapy or radiotherapy before starting the trial. Also, you cannot use other potentially phototoxic substances during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MR-Guided Focused Ultrasound (MRgFUS) is a safe method for treating brain conditions. This technique uses sound waves to target and destroy tumor cells without affecting nearby healthy tissue. Studies have found it to be non-invasive and generally well-tolerated by patients.

When combined with SONALA-001 (a type of aminolevulinic acid, or ALA), this ultrasound method has demonstrated good safety results. Previous trials found no damage to healthy brain tissue after treatment, suggesting that the treatment is safe when used correctly.

Since this trial is in its early stages, it primarily focuses on safety. The treatment is considered safe enough for human testing, but it is still closely monitored to ensure it is well-tolerated. Participants can be assured that their safety remains the main priority while exploring the potential benefits of the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain cancer because they combine innovative approaches to target tumors more precisely. Sonodynamic Therapy uses a special compound called SONALA-001 (ALA) that makes cancer cells sensitive to sound waves. When combined with MR-Guided Focused Ultrasound (MRgFUS), it allows doctors to target and destroy cancer cells with pinpoint accuracy, unlike traditional treatments that often affect both healthy and cancerous cells. This method could potentially reduce side effects and improve outcomes by focusing treatment directly on the tumor while sparing healthy brain tissue. Additionally, the unique dose and timing adjustments being tested aim to optimize the effectiveness and safety of the treatment.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that MR-Guided Focused Ultrasound (MRgFUS) with SONALA-001, a type of aminolevulinic acid, holds promise for treating brain cancer. In this trial, participants will join different arms to evaluate various combinations of MRgFUS and SONALA-001. Studies have found that MRgFUS can precisely target tumors without harming nearby healthy tissue. This method also opens the blood-brain barrier, allowing drugs to reach the tumor more easily. When combined with SONALA-001, this treatment can activate the drug directly in the tumor, enhancing its effectiveness. Early results suggest this approach could improve outcomes for individuals with recurring high-grade gliomas. ^{1 2 6 7 8}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

St. Joseph's Hospital and Medical Center, Phoenix

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade gliomas (brain tumors) that have recurred after standard therapy. Participants must be in relatively good health, not pregnant or breastfeeding, and willing to use effective contraception. They should not have serious bleeding disorders, heart conditions, certain infections, or an inability to undergo MRI.

Inclusion Criteria

I have recovered from chemotherapy side effects, except for possible hair loss or mild nerve pain.

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so.

My blood tests show my organs and bone marrow are working well.

Exclusion Criteria

I have been diagnosed with porphyria.

I do not have any active infections requiring IV antibiotics or known viral infections like HIV or active hepatitis B or C.

I am currently experiencing a severe worsening of my COPD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous ALA followed by sonodynamic therapy (SDT) with MRgFUS

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including radiographic and biological assessments

4-14 days

Multiple visits (in-person)

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• MR-Guided Focused Ultrasound device (MRgFUS)
• SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Trial Overview The study tests sonodynamic therapy using MR-guided focused ultrasound (MRgFUS) combined with a drug called ALA on patients with recurrent brain tumors. It's a first-in-human study assessing different energy doses of this treatment for safety and effectiveness.

How Is the Trial Designed?

Group I: Arm E Optimal energy and ALA dose Experimental Treatment 1 Intervention

In Arm E patients will receive treatment at the optimal energy and ALA dose determined form prior Arms.

Group II: Arm D MRgFUS alone Experimental Treatment 1 Intervention

In Arm D, MRgFUS treatment alone will be given at the optimal energy determined from previous Arms.

Group III: Arm C ALA Dose-escalation Experimental Treatment 1 Intervention

In Arm C, the MRgFUS power/energy dose will be fixed based on Arm A MTD/OBD, with the SONALA-001 dose escalation.

Group IV: Arm B Time-escalation Experimental Treatment 1 Intervention

In Arm B, the time-escalation cohort, the SONALA-001 and power/energy dose combination will be fixed. Participants will be enrolled into two time cohorts (2 days and 6 days post-SDT).

Group V: Arm A Energy Dose-escalation Experimental Treatment 1 Intervention

In Arm A, the dose-escalation cohort, there will be 3 cohorts of ascending MRgFUS power/energy dose combinations with a fixed SONALA-001 dose and fixed surgical time. Arm A will determine the power/energy dose combination for Arm B.

MR-Guided Focused Ultrasound device (MRgFUS) is already approved in United States for the following indications:

Approved in United States as MRgFUS for:

• Research use in clinical trials for recurrent high-grade glioma

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

SonALAsense, Inc.

Industry Sponsor

Trials

4

Recruited

450+

InSightec

Industry 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

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

In a study involving 24 patients, MRgFUS demonstrated significant efficacy in treating benign bone tumors, achieving complete ablation with minimal adverse effects, and effectively reducing pain in patients with metastatic bone disease.

The treatment resulted in 100% necrosis of ablated primary malignant tumors, indicating its potential as a safe and noninvasive option for managing both primary and metastatic bone tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance guided focused ultrasound for treatment of bone tumors. Singh, VA., Shah, SU., Yasin, NF., et al.[2018]

High frequency focused ultrasound (MRgFUS) is a promising non-invasive therapy for treating tumors, showing effectiveness and safety in initial clinical experiences with uterine fibroids, breast cancer, and fibroadenomas.

The use of MRI guidance enhances the precision of focused ultrasound treatments, making it a strong candidate for future applications in other tumor types, including liver and brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Magnetic resonance tomography guided focussed ultrasound surgery (MRgFUS) in tumor therapy--a new noninvasive therapy option]. Hengst, SA., Ehrenstein, T., Herzog, H., et al.[2018]

The novel TRANS-FUSIMO Treatment System (TTS) successfully quantifies key parameters for liver tumor ablation using Magnetic Resonance Guided Focused Ultrasound (MRgFUS), achieving a maximum deviation of only 0.16 seconds from planned sonication duration, which is crucial for safe and effective treatment.

The study demonstrated that the sonication process is consistent across different operators, indicating reliability in the system's performance, which is essential for clinical applications and quality assurance in medical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation. Mihcin, S., Karakitsios, I., Le, N., et al.[2018]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a study involving 30 women with breast cancer, MRgFUS treatment resulted in an impressive average of 96.9% tumor necrosis, indicating its high effectiveness in ablating breast carcinomas.

The procedure was well tolerated with minimal adverse effects, especially when performed under local anesthesia, suggesting it could be a safe noninvasive alternative to traditional surgical methods like lumpectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. Furusawa, H., Namba, K., Thomsen, S., et al.[2022]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective incisionless treatment for centrally located brain lesions in adolescents and young adults, with no complications reported in a study of 5 patients aged 15-22.

The procedure successfully achieved thermoablation in 4 out of 5 cases, leading to improvements in symptoms such as seizure control, demonstrating its potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. Tierney, TS., Alavian, KN., Altman, N., et al.[2022]

In a study involving 13 patients with painful bone metastases, MRgFUS was found to be a safe procedure, with no severe adverse events reported during the 6-month follow-up period.

The treatment showed initial efficacy, as 10 out of 12 patients experienced significant pain relief and reduced need for pain medication after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases--preliminary clinical experience. Catane, R., Beck, A., Inbar, Y., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. Bunevicius, A., McDannold, NJ., Golby, AJ.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11135048/

Focused ultrasound as a treatment modality for gliomas - PMC Evaluate the safety of the ExAblate Model 4,000 Type 2 used as a tool to disrupt the BBB in patients with high grade glioma undergoing standard ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05879120

NCT05879120 | Randomized Study of Neo-adjuvant and ... To assess efficacy of BBB opening as measured by drug levels of pembrolizumab in target brain tumor tissue, comparing Exablate MRgFUS BBB opening during neo- ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT07076472

NCT07076472 | Sonodynamic Therapy With SONALA-001 ... MRgFUS is an image-guided, non-invasive technique that uses high energy ultrasound from the Exablate 4000 Type 2.0 device to kill tumors without damaging ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950329925000633

Regulation of the brain tumor microenvironment by focused ... From the perspective of the brain tumor microenvironment, FUS can produce mechanical and thermal effects by delivering sound waves to brain ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03616860?term=NCT03616860&limit=10&rank=1

Assessment of Safety and Feasibility of ExAblate Blood ... The purpose of this study is to evaluate the safety of blood-brain barrier (BBB) disruption in adult patients with a first presentation of a glioblastoma (GBM) ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The ExAblate Model 4000 Type 1.0 System (“ExAblate Neuro” or “the system”) is a transcranial, magnetic resonance, image-guided focused ultrasound ...

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

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The Exablate system platform is intended to ablate brain tissue with focused ultrasound and operates in conjunction with an MRI scanner that is used for ...