Ultrasound-Enhanced Radiation Therapy for Breast Cancer

Overseen By Gregory Czarnota, MD, Ph D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

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)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new breast cancer treatment using MRI-guided ultrasound and microbubbles to enhance radiation therapy effects. The goal is to determine if this approach can improve radiation treatment effectiveness for certain breast cancer types. It targets individuals with confirmed breast cancer, from early to advanced stages, who are scheduled for radiation therapy. Participants must be able to undergo MRI scans and tolerate radiation treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 (a heart rhythm condition), you may not be eligible to participate.

What prior data suggests that this MRI-guided ultrasound stimulated microbubble treatment is safe for humans?

Earlier studies have shown promising safety results for MRI-guided ultrasound with microbubbles. One study focused on breast cancer and found that patients tolerated it well, with no serious side effects directly linked to the treatment. This suggests that combining ultrasound and microbubbles with radiation might safely enhance the effects of cancer therapy. As this is an early-stage trial, safety remains the main concern, and researchers closely monitor for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for breast cancer because it introduces a novel technique that could enhance the effectiveness of radiation therapy. Unlike standard treatments, which typically include surgery, chemotherapy, and radiation alone, this approach uses ultrasound to activate microbubbles that help target and amplify the impact of radiation on cancer cells. This method promises to improve precision and potentially reduce damage to surrounding healthy tissue, offering a more targeted and potentially safer treatment option for patients.

What evidence suggests that MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment could be effective for breast cancer?

Studies have shown that MRI-guided ultrasound with tiny bubbles can enhance the effectiveness of radiation therapy for tumors. In this trial, all participants will receive the MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment combined with Radiation Therapy. Research indicates that this combination can increase tumor cell destruction by 10 to 40 times compared to radiation alone. Early human trials demonstrated that this treatment is safe and effective for targeting breast cancer. Focused ultrasound and tiny bubbles amplify the effects of radiation, potentially leading to better patient outcomes. These findings offer hope that this new approach could improve treatment for those with breast cancer. ^{1 2 4 6 7}

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 individuals with chest-wall or locally advanced breast cancer. Specific eligibility details are not provided, but typically participants must meet certain health criteria and have a type of cancer that the study targets.

Inclusion Criteria

My kidney function is normal or nearly normal.

Weight < 140 kg

My breast cancer is at an early or locally advanced stage (IIA-IIIC) or stage IV.

Exclusion Criteria

Presence of metallic or breast implants

Unable to have a contrast-enhanced MRI scan

I have had anthracycline or taxane chemotherapy in the last 5 days.

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 combined with LINAC-based radiation therapy

Duration not specified

Multiple visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment

Trial Overview The study tests if MRI-guided ultrasound stimulated microbubbles can boost the effectiveness of radiation therapy in treating breast cancer. Participants will receive this novel treatment alongside standard external beam radiotherapy from a LINAC device.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 2 Interventions

All biopsy confirmed breast cancer patients undergoing MRI-Ultrasound Stimulated Microbubble Radiation Treatment plus Radiation Therapy.

MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment is already approved in Canada for the following indications:

Approved in Canada as MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for:

• Locally Advanced Breast Cancer
• Chest-Wall Tumors

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

In a study involving mice with breast cancer tumors, ultrasound-stimulated microbubbles combined with radiation treatment showed significant additive effects, leading to increased tumor cell death and vascular disruption.

The treatment resulted in delayed tumor growth and enhanced anti-tumor effects, suggesting that ultrasound-driven microbubbles could serve as a novel targeted therapy to improve the efficacy of radiation in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast tumor response to ultrasound mediated excitation of microbubbles and radiation therapy in vivo. Lai, P., Tarapacki, C., Tran, WT., et al.[2020]

Magnetic resonance-guided focused ultrasound (MRgFUS) therapy for uterine fibroids has a relatively low incidence of serious complications, with major adverse events occurring in only 0.41% of cases across 43 studies analyzed.

The most common adverse events reported include pain, skin burns, urinary tract infections, and sciatic neuropraxia, with an overall adverse event occurrence rate of 24.67%, indicating that while MRgFUS is generally safe, some side effects do occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives. Kociuba, J., Łoziński, T., Zgliczyńska, M., et al.[2023]

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]

The combination of ultrasound-stimulated microbubbles (USMB) with radiation therapy (XRT) significantly increased cell death in breast cancer tumors, showing a strong efficacy in enhancing treatment outcomes (p = 0.0006).

This combined treatment also led to reduced tumor vascularization and increased tumor hypoxia, indicating a mechanism by which USMB enhances the effectiveness of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of Breast Cancer Xenograft Model. Sharma, D., Hussein, F., Law, N., et al.[2022]

Focused ultrasound (FUS) can enhance the effects of radiation therapy (RT) by allowing targeted delivery of ultrasound energy to cancer cells, potentially reducing the required radiation doses and minimizing damage to surrounding healthy tissue.

Recent studies show that using ultrasound-stimulated microbubbles can further improve RT by acting as a radioenhancer or delivery system for radiosensitizing agents, leading to increased cell death and better tumor control in preclinical models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound and Ultrasound Stimulated Microbubbles in Radiotherapy Enhancement for Cancer Treatment. Leong, KX., Sharma, D., Czarnota, GJ.[2023]

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]

Low-intensity MR-guided focused ultrasound combined with microbubbles shows promise for safely delivering drugs to the central nervous system by temporarily opening the blood-brain barrier, which is crucial for treating brain cancers.

Preclinical studies have demonstrated the safety and preliminary efficacy of this method in animal models, suggesting it could be a noninvasive and repeatable approach for targeting drug delivery in neuro-oncology patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. Meng, Y., Suppiah, S., Surendrakumar, S., et al.[2020]

In a phase 1 trial involving 8 patients with breast cancer, the combination of MRI-guided focused ultrasound (FUS) with microbubble (MB) treatment and fractionated radiotherapy (RT) resulted in a complete response in all evaluable patients after at least 3 months, indicating strong potential for radiosensitization.

The treatment was found to be safe, with only mild acute toxicities observed (grade 2 dermatitis in 1 site and grade 1 in 8 sites), all of which resolved by 3 months, and no late effects or significant toxicity related to either RT or FUS-MB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel MRI-guided focussed ultrasound stimulated microbubble radiation enhancement treatment for breast cancer. Dasgupta, A., Saifuddin, M., McNabb, E., et al.[2023]

Using ultrasound contrast agent microbubbles with MRI-guided focused ultrasound (MRgFUS) allows for effective mild hyperthermia (42°C) with reduced power levels, demonstrating accurate temperature control in both muscle and tumors.

The combination of microbubbles and MRgFUS significantly increased drug uptake of liposomal doxorubicin in muscle tissue compared to conventional heating, indicating a potential for improved drug delivery, although this effect was not observed in tumor tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbubble-assisted MRI-guided focused ultrasound for hyperthermia at reduced power levels. Santos, MA., Wu, SK., Li, Z., et al.[2019]

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]

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]

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]

Citations

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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 ...

2. 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.

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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 ...

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A Novel Strategy to Enhance Radiotherapy Efficacy 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 focused- ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04431674

NCT04431674 | Novel MRI-Guided Ultrasound Stimulated ... The primary aim of this research is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment and radiation in patients with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06633601

MRI-Guided Ultrasound Stimulated Microbubbles ... In this study, locally advanced breast cancer (LABC) and breast/chest wall tumours not managed by surgery, patients will receive MRI-guided ...