Focused Ultrasound Radiosensitization for Melanoma

Overseen By Dr. Gregory Czarnota, MD, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: Immunotherapy

Must not be taking: QTc prolonging drugs

Disqualifiers: Pregnancy, Severe cardiovascular, Neurological, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

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 tests a new method for treating skin cancer, including melanoma, using the Sonalleve Focused Ultrasound Device combined with radiation therapy. The researchers aim to determine if this combination is safe and effective for patients. Individuals diagnosed with skin cancer, including those with metastatic cancer, who are already receiving radiation therapy might be suitable candidates. Participants must have a target lesion (tumor area) visible on an MRI scan and accessible for treatment. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking medications known to cause QTc prolongation, like certain antidepressants or antipsychotics, you may be excluded from participating.

What prior data suggests that the Sonalleve Focused Ultrasound Device is safe for use in melanoma treatment?

Research has shown that the Sonalleve Focused Ultrasound Device has undergone safety testing in various situations. It has effectively treated conditions like prostate cancer and osteoid osteoma, with minimal side effects. Specifically, it significantly reduced pain in osteoid osteoma patients without the need for painkillers.

The ultrasound-enhancing agent Definity, commonly used in imaging tests, has also demonstrated safety. It is considered safe even for individuals with heart and lung issues. No major safety differences have been observed between older and younger users of Definity.

Although specific data on using this focused ultrasound device for melanoma treatment is not yet available, its previous safe use in other conditions is promising. As this trial is in an early stage, the primary goal is to ensure safety, and any side effects will be closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for melanoma, which typically involve surgery, chemotherapy, or immunotherapy, the Sonalleve Focused Ultrasound Device uses a novel method by combining MRI-guided focused ultrasound with microbubble treatment and radiation therapy. This approach allows for precise targeting of cancer cells, potentially enhancing the effectiveness of radiation therapy. Researchers are excited because this method may minimize damage to surrounding healthy tissue and improve treatment outcomes. Additionally, this technique could offer a less invasive option with fewer side effects compared to traditional therapies.

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

Research has shown that the Sonalleve Focused Ultrasound Device, which participants in this trial will receive, has been used to treat tumors in various situations. Although limited information exists specifically about melanoma, this technology has shown potential for non-invasive tumor removal by using sound waves to target tumors. In past cases, the device reduced pain and the need for pain medication in conditions like osteoid osteoma, a type of bone tumor. The focused ultrasound works by directing high-energy sound waves at the tumor, which can help shrink or destroy it. In this trial, the method is used alongside radiotherapy to potentially enhance treatment effectiveness for melanoma. Early results suggest that this combination might improve patient outcomes, but more research is needed to confirm its success in treating melanoma specifically. ^{6 7 8 9 10}

Who Is on the Research Team?

Gregory J Czarnota, PhD, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with any stage of malignant melanoma who are referred for various types of radiotherapy and may be on immunotherapy. They must weigh less than 140kg, have a target lesion visible by MRI that's accessible for treatment, normal kidney function or mild impairment, and not be pregnant or breastfeeding. Participants need to use effective contraception if they can reproduce.

Inclusion Criteria

I am referred for a specific type of radiotherapy.

My cancer can be targeted with a specific type of focused ultrasound.

I have a confirmed diagnosis of skin cancer, including melanoma or non-melanoma types.

Exclusion Criteria

I need help with my daily activities due to my health condition.

My blood pressure is very high (over 100 mmHg diastolic).

I am using birth control if I can have children.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Multiple visits (in-person)

Long-term follow-up

Participants are evaluated for tumor response radiologically

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Definity
• Sonalleve Focused Ultrasound Device

Trial Overview The study tests the combination of an MRI-guided focused ultrasound device called Sonalleve and microbubble therapy using Definity with standard radiotherapy to see if it's safe and improves treatment outcomes in melanoma patients.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 2 Interventions

Malignant Melanoma patients undergoing MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy

Sonalleve Focused Ultrasound Device is already approved in European Union, United States for the following indications:

Approved in European Union as Sonalleve MR-HIFU for:

• Uterine fibroids
• Bone metastasis
• Desmoid tumors

Approved in United States as Sonalleve MR-HIFU for:

• Osteoid osteomas in the extremities

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Terry Fox Research Institute

Collaborator

Trials

11

Recruited

1,600+

Published Research Related to This Trial

High intensity focused ultrasound (HIFU) treatment for local recurrence of prostate cancer after radiotherapy showed a five-year progression-free survival rate of 44%, indicating its potential efficacy in managing this condition.

However, patients experienced significant adverse effects, including a 44% rate of urinary incontinence and a 30% rate of urethral stricture or bladder neck stenosis, highlighting the importance of discussing these risks before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Locally recurrent prostatic adenocarcinoma after exclusive radiotherapy: results of high intensity focused ultrasound]. Poissonnier, L., Murat, FJ., Belot, A., et al.[2010]

High-intensity focused ultrasound (HIFU) shows promise as a salvage therapy for localized prostate cancer recurrence after radiation treatments, with a 5-year biochemical disease-free survival (bDFS) rate of 52% among 22 patients followed for a median of 24 months.

While HIFU has comparable side effects to other salvage treatments, including urethral stricture and urinary incontinence, it remains a viable option for patients with localized recurrence after previous radiation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after external beam radiation, brachytherapy or proton therapy. Uchida, T., Shoji, S., Nakano, M., et al.[2022]

The study involving 17 participants with advanced liver cancer demonstrated that Sonazoid-assisted high-intensity focused ultrasound (HIFU) is safe, with no serious side effects reported, although mild increases in liver enzyme levels and skin edema were observed in some patients.

The treatment showed promising efficacy, with 5.9% of patients achieving complete response immediately after treatment and a median time to disease progression of 11 months, indicating that further research is needed to fully assess the therapeutic benefits of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study. Zhou, H., Li, F., Luo, L., et al.[2023]

In a Phase II/III clinical trial involving 402 patients with localized prostate cancer, high-intensity focused ultrasound (HIFU) demonstrated a high negative biopsy rate of 87.2%, indicating its efficacy as a treatment option.

The study suggests that HIFU is a viable primary treatment for localized prostate cancer, especially in low-risk patients, who showed a 92.1% negative biopsy rate, with a mean follow-up duration of over a year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. Thüroff, S., Chaussy, C., Vallancien, G., et al.[2016]

The study involved 57 patients (35 treated with the prototype Sonablate HIFU1 and 22 with the newer Sonablate-200 HIFU2) and showed significant improvements in International Prostate Symptom Score (IPSS) and quality of life (QOL) scores after treatment, indicating effective symptom relief for benign prostatic hyperplasia.

HIFU2 demonstrated superior clinical outcomes compared to HIFU1, with significant improvements in maximum flow rate and prostatic volume at 12 months post-treatment, while only minor complications were reported, highlighting its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of high-intensity focused ultrasound for treating benign prostatic hyperplasia: preliminary report. Uchida, T., Muramoto, M., Kyunou, H., et al.[2019]

High-intensity focused ultrasound (HIFU) treatment for localized prostate cancer in an Afro-Caribbean population showed promising oncological results, with 73.5% of patients having negative biopsies after treatment.

The procedure demonstrated a low rate of genitourinary side effects, with urinary incontinence occurring in 7.5% and erectile dysfunction in 13.2% of patients, indicating it is a safe option for this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[High-intensity focused ultrasound for locally prostate cancer: An Afro-Caribbean single-center study]. Deleuze, C., Blanchet, P., Gourtaud, G., et al.[2021]

High-intensity focused ultrasound (HIFU) was used to treat 43 patients with localized prostate cancer, but the treatment showed significant rates of oncological failure, with 46% failure in the primary group and 75% using FDA criteria.

Despite being considered a minimally invasive treatment, HIFU resulted in notable complications, including urethral strictures and fistulae, leading the researchers to suspend their program pending further evidence of its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound for localized prostate cancer: initial experience with a 2-year follow-up. Challacombe, BJ., Murphy, DG., Zakri, R., et al.[2019]

Transrectal high-intensity focused ultrasound (HIFU) is a safe and effective treatment for prostate cancer, showing high biochemical disease-free rates of 86%, 81%, and 79% at 1, 2, and 3 years for localized cases.

In advanced prostate cancer patients, HIFU combined with androgen ablation significantly reduced prostate volume and serum PSA levels, with no serious complications reported, highlighting its safety and efficacy as a minimally invasive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transrectal high-intensity focused ultrasound with the Sonablate 500 for the treatment of prostate cancer]. Lu, J., Chen, ZY., Wang, W., et al.[2007]

Focused ultrasound (FUS) combined with radiation therapy (RT) significantly enhances the effectiveness of cancer treatment, showing a 4.6 times greater inhibition of tumor growth in a mouse model compared to RT alone.

The study demonstrated that FUS can improve the radiosensitization of prostate cancer cells, leading to better treatment outcomes, which suggests a promising non-invasive approach for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Developed MRI-Guided Focused Ultrasound System in 7 T Small Animal MRI and Proof-of-Concept in a Prostate Cancer Xenograft Model to Improve Radiation Therapy. Zhang, X., Greiser, S., Roy, U., et al.[2023]

High-intensity focused ultrasound (HIFU) is a promising non-invasive treatment option for various solid tumors, including those in the pancreas, liver, and prostate, showing potential as an alternative to traditional oncologic therapies.

HIFU can be combined with imaging techniques like MRI and ultrasound for real-time monitoring during treatment, enhancing its safety and efficacy while minimizing complications associated with open surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Introduction to High Intensity Focused Ultrasound: Systematic Review on Principles, Devices, and Clinical Applications. Izadifar, Z., Izadifar, Z., Chapman, D., et al.[2020]

High-intensity focused ultrasound (HIFU) is a safe and non-invasive treatment option for advanced pancreatic cancer, as shown in a study of 224 cases with no severe complications reported.

While some patients experienced mild side effects like increased serum amylase levels and gastrointestinal dysfunction, the overall safety profile was positive, indicating that careful preparation and execution are essential for successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer. Wang, K., Zhu, H., Meng, Z., et al.[2022]

Citations

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Sonalleve MR-HIFU (H190003) 2024 PAC Executive ... The Sonalleve MR-HIFU System is designed to non-invasively deliver acoustic energy to targeted anatomy. The system combines a high energy ...

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Focused Ultrasound Radiosensitization for Melanoma These studies suggest that HIFU has been evaluated for safety in various contexts, but specific safety data for melanoma treatment using the devices mentioned ( ...

3. fusfoundation.org fusfoundation.org/the-technology/timeline-of-focused-ultrasound/

Timeline of Focused Ultrasound Profound Medical's Sonalleve system received the CE mark for the treatment of desmoid tumors. World-First for Metastatic Breast Cancer In a first-in-world ...

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FDA Approves Sonalleve MR-HIFU System for Osteoid ... Results showed that there was a statistically significant decrease in pain scores within 4 weeks of treatment, and no pain medication was used ...

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MR-guided high-intensity focused ultrasound for ... MR-HIFU is a unique noninvasive tumour ablation technique because of the combination of focused ultrasound with real-time MR guidance.

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Safety Profile of DEFINITY® for Medical Imaging DEFINITY® is demonstrated to be safe in patients with a high prevalence of cardiopulmonary disease and pulmonary hypertension.

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Advances of Drug-Loaded Microsphere Technology for ... Research indicates that microspheres sized 100–300 μm achieve an optimal tumor necrosis rate of 85–92% in prostate cancer embolization.

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Press Release Details - Lantheus Investor Relations New clinical outcomes data for DEFINITY® Vial for (Perflutren Lipid Microsphere) Injectable Suspension in intensive care unit patients will be presented at the ...

9. diagnosticimaging.com diagnosticimaging.com/view/fda-pediatric-use-ultrasound-enhancing-agent-suboptimal-echocardiogram-cases

FDA Approves Pediatric Use of Ultrasound-Enhancing Agent ... One study demonstrated enhanced detection of wall motion abnormalities in 70 percent of patients and improved determination of ejection fraction ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/021064s025s029lbl.pdf

Definity - accessdata.fda.gov No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not ...