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

Trial Summary

What is the purpose of this trial?

The objective of this study is to examine the safety profile and therapeutic efficacy of MRI-guided focused ultrasound microbubble therapy and radiotherapy in humans.

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 data supports the idea that Focused Ultrasound Radiosensitization for Melanoma is an effective treatment?

The available research shows that high-intensity focused ultrasound (HIFU) has been studied primarily for prostate cancer, not melanoma. These studies indicate that HIFU can be effective for treating prostate cancer, especially in cases where the cancer has returned after other treatments. However, there is no specific data provided here about its effectiveness for melanoma, so we cannot conclude its effectiveness for melanoma based on this information. ^{1 2 3 4 5}

What safety data exists for focused ultrasound radiosensitization in melanoma treatment?

The provided research does not directly address the safety of focused ultrasound radiosensitization specifically for melanoma. However, it includes safety evaluations of high-intensity focused ultrasound (HIFU) in other conditions such as prostate cancer, pancreatic cancer, benign prostatic hyperplasia, and advanced liver malignant lesions. These studies suggest that HIFU has been evaluated for safety in various contexts, but specific safety data for melanoma treatment using the devices mentioned (Definity, Perflutren Lipid Microsphere, Sonalleve Focused Ultrasound Device, Sonalleve MR-HIFU, Philips Sonalleve MR-HIFU) is not provided in the research listed. ^{4 6 7 8 9}

Is the treatment Sonalleve Focused Ultrasound Device a promising treatment for melanoma?

Yes, the Sonalleve Focused Ultrasound Device is a promising treatment because focused ultrasound can target and destroy tumor cells without surgery. It can also enhance the effects of radiation therapy, making it a powerful tool in cancer treatment. ^{3 4 5 10 11}

Research Team

Gregory J Czarnota, PhD, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Locally recurrent prostatic adenocarcinoma after exclusive radiotherapy: results of high intensity focused ultrasound]. [2010]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound for localized prostate cancer: initial experience with a 2-year follow-up. [2019]

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

High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. [2016]

5. China pubmed.ncbi.nlm.nih.gov

[Transrectal high-intensity focused ultrasound with the Sonablate 500 for the treatment of prostate cancer]. [2007]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer. [2022]

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

Clinical outcome of high-intensity focused ultrasound for treating benign prostatic hyperplasia: preliminary report. [2019]

8. England 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. [2023]

9. France pubmed.ncbi.nlm.nih.gov

[High-intensity focused ultrasound for locally prostate cancer: An Afro-Caribbean single-center study]. [2021]

10. Switzerland 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. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

An Introduction to High Intensity Focused Ultrasound: Systematic Review on Principles, Devices, and Clinical Applications. [2020]