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?

The objective of this study is to demonstrate the efficacy and response of novel Magnetic Resonance Imaging (MRI)-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device.

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.

Is the ultrasound and microbubble radiation treatment generally safe for humans?

MRI-guided focused ultrasound (MRgFUS) is a noninvasive treatment that has been used safely for conditions like uterine fibroids and bone metastases, with the ability to target and treat tissue without harming nearby healthy areas. It is considered relatively painless and can be done on an outpatient basis, showing promise in treating various cancers. ^{1 2 3 4 5}

What makes the ultrasound and microbubble radiation treatment for breast cancer unique compared to other treatments?

This treatment combines MRI-guided focused ultrasound (a noninvasive method using sound waves to target and destroy tumor tissue) with microbubbles to enhance the effects of radiation therapy, offering precise targeting and real-time monitoring, which may improve treatment accuracy and reduce damage to healthy tissue. ^{1 3 5 6 7}

What data supports the effectiveness of the treatment Ultrasound and Microbubble Radiation Treatment for Breast Cancer?

Research shows that MRI-guided focused ultrasound (MRgFUS) has been effective in treating various tumors, including breast cancer, by precisely targeting and destroying tumor tissue without harming nearby healthy tissue. This method has been successfully used for uterine fibroids and bone metastases, indicating its potential for breast cancer treatment. ^{1 2 3 5 6}

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

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]

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]

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Robotic system for top to bottom MRgFUS therapy of multiple cancer types. [2022]

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

Magnetic Resonance-Guided Focused Ultrasound Versus Conventional Radiation Therapy for Painful Bone Metastasis: A Matched-Pair Study. [2017]

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

ExAblate magnetic resonance-guided focused ultrasound system in multiple body applications. [2010]

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

MRI-guided focused ultrasound surgery. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[Magnetic resonance tomography guided focussed ultrasound surgery (MRgFUS) in tumor therapy--a new noninvasive therapy option]. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Magnetic resonance guided focused high frequency ultrasound ablation for focal therapy in prostate cancer - phase 1 trial. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical and future applications of high intensity focused ultrasound in cancer. [2022]