Ultrasound and Microbubble Radiation Treatment for Breast Cancer

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

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Antidepressants, Antiarrhythmics, Antipsychotics, others

Disqualifiers: Pregnancy, Metallic implants, Severe cardiovascular, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Varies

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new breast cancer treatment combining radiation therapy with a special ultrasound technique using tiny bubbles, known as MRI-guided ultrasound stimulated microbubble treatment. The goal is to determine if this approach can enhance the effectiveness of radiation treatment. Individuals diagnosed with certain types of breast cancer and planning to receive radiation therapy might be suitable candidates. The study seeks participants who can communicate during the procedure and meet specific health criteria. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

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, you may not be eligible to participate.

What prior data suggests that the MRI-guided ultrasound stimulated microbubble treatment is safe for breast cancer patients?

Research has shown that MRI-guided ultrasound with microbubbles is generally safe. In previous studies, this treatment was tested on breast cancer patients and was well-tolerated, with no major safety issues reported.

One study examined the safety of combining microbubble treatment with radiation and found no severe side effects, suggesting safety when used with radiation therapy.

This trial is in a phase that evaluates both safety and effectiveness, indicating it has already passed initial safety tests in earlier studies. This level of testing helps ensure treatments are usually safe for a broader population. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines MRI-guided ultrasound-stimulated microbubble therapy with traditional radiation therapy to treat breast cancer. Unlike standard treatments, which typically involve surgery, chemotherapy, and radiation, this approach uses microbubbles that are activated by ultrasound to enhance the delivery and effectiveness of radiation therapy directly to the tumor. This targeted method could potentially increase the precision of cancer treatment, reducing damage to surrounding healthy tissues and improving outcomes. The integration of MRI guidance allows for real-time monitoring and adjustment, making the treatment more personalized and potentially more effective.

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

Research has shown that MRI-guided ultrasound with microbubbles can significantly enhance the effects of radiation therapy for breast cancer. In earlier patients, this method increased cancer cell death by 10 to 40 times when combined with standard radiation treatment. Studies have also demonstrated that this approach is safe and effective in early human trials. In this trial, participants will receive MRI-guided ultrasound-stimulated microbubble treatment alongside radiation therapy. These findings suggest that this treatment could be a promising way to enhance the effectiveness of radiation therapy in combating breast cancer. ^{1 2 3 4 5}

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 patients with advanced breast cancer affecting the chest wall. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be required to have a particular stage or type of breast cancer.

Inclusion Criteria

Able to communicate sensation during the procedure

I weigh less than 140 kg.

My target lesion can be reached for a specific ultrasound treatment.

Exclusion Criteria

Metallic or breast implants

Allergy to Definity microbubbles

I haven't had heart disease or unstable blood pressure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

Varies

Multiple visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Visits at 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year

What Are the Treatments Tested in This Trial?

Interventions

• LINAC radiation therapy device
• MRI-guided ultrasound stimulated microbubble treatment

Trial Overview The study tests a new treatment combining MRI-guided ultrasound (using Sonalleve device) with microbubbles (Definity) to boost the effectiveness of standard radiation therapy from a linear accelerator in treating advanced breast cancer.

How Is the Trial Designed?

Group I: Experimental: Treatment Arm Experimental Treatment 2 Interventions

All biopsy confirmed breast cancer patients undergoing MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy

LINAC radiation therapy device is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Linear Accelerator Radiation Therapy Device for:

• Breast cancer
• Chest-wall cancer

Approved in United States as External Beam Radiotherapy for:

• Breast cancer
• Various cancers

Approved in European Union as Linear Accelerator Radiation Therapy Device for:

• Breast cancer
• Various cancers

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

MRI-guided focused ultrasound (MRgFUS) is a noninvasive method that allows precise targeting and ablation of tumors while preserving surrounding healthy tissue, making it a promising alternative to traditional surgical methods and radiation therapy.

Currently approved for treating uterine fibroids, MRgFUS is being tested in clinical trials for various cancers and has the potential to enhance drug delivery and gene therapy by temporarily altering cell membrane permeability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided focused ultrasound surgery. Jolesz, FA.[2022]

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]

Magnetic resonance-guided high frequency focused ultrasound (MRgFUS) is a safe and feasible method for noninvasively treating low-intermediate risk prostate cancer, with acceptable short-term oncologic outcomes observed in a study of eight patients.

After treatment, 60% of target lesions showed no disease on biopsy, and the mean PSA levels decreased significantly from 5.06 ng/ml to 3.4 ng/ml at 6 months, indicating effective disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance guided focused high frequency ultrasound ablation for focal therapy in prostate cancer - phase 1 trial. Ghai, S., Perlis, N., Lindner, U., et al.[2020]

High intensity focused ultrasound (HIFU) is a non-invasive treatment option for various tumors, showing promising safety and feasibility in clinical studies over the past decade.

HIFU may serve as a viable alternative or complement to traditional cancer treatments like surgery and chemotherapy, and future developments could enable it to facilitate targeted drug and gene delivery for localized cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and future applications of high intensity focused ultrasound in cancer. Al-Bataineh, O., Jenne, J., Huber, P.[2022]

In a study of 63 patients with painful bone metastasis, magnetic resonance-guided focused ultrasound (MRgFUS) demonstrated a significantly higher pain relief response rate at 1 week post-treatment (71%) compared to conventional radiation therapy (RT) (26%).

While both MRgFUS and RT were effective overall, MRgFUS provided faster pain palliation, suggesting it could be a promising first-line treatment option for selected patients with bone metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Focused Ultrasound Versus Conventional Radiation Therapy for Painful Bone Metastasis: A Matched-Pair Study. Lee, HL., Kuo, CC., Tsai, JT., et al.[2017]

A new robotic system for Magnetic Resonance guided Focused Ultrasound (MRgFUS) therapy has been developed and shown to be compatible with clinical MRI scanners, ensuring safety during treatment.

The system effectively created targeted lesions in excised tissue, demonstrating its efficacy in delivering precise ultrasound therapy without causing unwanted heating or magnetic interference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic system for top to bottom MRgFUS therapy of multiple cancer types. Antoniou, A., Giannakou, M., Evripidou, N., et al.[2022]

Focused ultrasound surgery (FUS) is a noninvasive treatment that effectively destroys targeted tissues while protecting surrounding areas, making it a safe option for patients.

When combined with magnetic resonance guidance (MRgFUS), this technique allows for real-time monitoring and personalized treatment, showing promising results in conditions like uterine fibroids and potential applications in prostate and liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ExAblate magnetic resonance-guided focused ultrasound system in multiple body applications. Dick, EA., Gedroyc, WM.[2010]

Citations

1. nature.com nature.com/articles/s41598-023-40551-5

Novel MRI-guided focussed ultrasound stimulated ... Here we report the first human trial of using magnetic resonance imaging (MRI) guided FUS-MB treatment in the treatment of breast malignancies.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38758967/

A Phase 1 clinical trial The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04431674

NCT04431674 | Novel MRI-Guided Ultrasound Stimulated ... The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in ...

4. journals.plos.org journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004408

Radiation enhancement using focussed ultrasound-stimulated ... The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0360301623055025

Results from the Prospective Phase I Clinical Trial of MR ... Preclinical in vitro and in vivo studies have demonstrated that tumor cell death can be enhanced 10- to 40-fold when radiotherapy (RT) is combined with ...