Contrast-Enhanced Ultrasound for Identifying Breast Masses

Recruiting at 1 trial location

Overseen By Janet Jaime

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Southern California

Disqualifiers: Pulmonary hypertension, Pregnant, Neoadjuvant chemotherapy, others

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

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if contrast-enhanced ultrasound (CEUS) can identify whether a breast mass is benign or malignant. The ultrasound uses sound waves and a contrast agent, such as Perflutren Lipid Microspheres or Sulfur Hexafluoride Lipid Microspheres, to produce clearer images. The goal is to assess if this method can reduce the need for more invasive biopsies. Women with newly diagnosed breast masses recommended for biopsy and assigned specific BIRADS categories by standard ultrasound may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to experience this innovative diagnostic approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are undergoing neoadjuvant chemotherapy, you cannot participate in the trial.

What prior data suggests that contrast-enhanced ultrasound is safe for identifying breast masses?

Research has shown that both perflutren and sulfur hexafluoride are generally safe for enhancing ultrasound images. Perflutren improves heart imaging effectively and safely, without the use of radiation.

Sulfur hexafluoride also maintains a strong safety record. Serious reactions are very rare and typically occur within 30 minutes of use. One study found a death rate of only 0.03% for patients using this agent, which is lower than for those not using it.

The FDA has already approved both agents for other uses, supporting their safety. Overall, they are well-tolerated, with few side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of contrast-enhanced ultrasound (CEUS) with Perflutren Lipid Microspheres and Sulfur Hexafluoride Lipid Microspheres for identifying breast masses because this method offers a unique approach to diagnosis. Unlike traditional imaging methods like mammography or MRI, CEUS provides real-time, dynamic imaging of blood flow and tissue perfusion without radiation exposure. The use of these specific contrast agents can potentially enhance the clarity and detail of ultrasound images, making it easier to distinguish between benign and malignant masses. This could lead to faster, more accurate diagnoses and reduce the need for invasive biopsies, which is a significant advancement in breast cancer diagnostics.

What evidence suggests that contrast-enhanced ultrasound is effective for identifying breast masses?

Research has shown that contrast-enhanced ultrasound (CEUS) can help differentiate between non-cancerous and cancerous breast lumps. In this trial, participants will receive a contrast tracer, either Perflutren Lipid Microspheres or Sulfur Hexafluoride Lipid Microspheres, as part of the CEUS scan. Studies have found that CEUS with Perflutren Lipid Microspheres reduces unnecessary biopsies for non-cancerous lumps. Similarly, Sulfur Hexafluoride Lipid Microspheres have aided in better diagnosing, staging, and monitoring breast cancer. Both methods use tiny bubbles to clarify ultrasound images, allowing doctors to see breast lumps in more detail. Overall, evidence suggests these contrast agents could make breast ultrasound exams more accurate and less invasive. ^{2 6 7 8 9}

Who Is on the Research Team?

Bino A Varghese, PhD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for individuals with breast masses that need to be checked if they're benign (not cancer) or malignant (cancer). It's not specified who can't join, but typically those with allergies to the contrast agents used or certain health conditions may be excluded.

Inclusion Criteria

My breast mass is suspicious and needs a biopsy.

I am female.

Exclusion Criteria

I am a woman currently receiving chemotherapy before surgery.

I am allergic to perflutren.

I am a woman under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Imaging

Patients receive a contrast agent intravenously and undergo CEUS scan over 60-90 minutes

1 day

1 visit (in-person)

Analysis

Development and assessment of radiomics-based ML classifier framework and TIC analysis

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after diagnostic imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Perflutren Lipid Microspheres
• Sulfur Hexafluoride Lipid Microspheres

Trial Overview The study is testing whether a special type of ultrasound called CEUS, using Sulfur Hexafluoride and Perflutren Lipid Microspheres as contrast agents, can help tell apart non-cancerous from cancerous breast lumps without needing a biopsy.

How Is the Trial Designed?

Group I: Diagnostic (contrast agent, CEUS) Experimental Treatment 3 Interventions

Patients receive a contrast tracer (Lumason or DEFINITY) IV and then undergo CEUS scan over 60-90 minutes.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 72 women with suspected breast lesions, the use of contrast agents during color Doppler ultrasound significantly improved the ability to differentiate between benign and malignant tumors, with 78.1% of malignant tumors showing a hypervascularity pattern.

The contrast agents enhanced the sensitivity and negative predictive value of ultrasound signals, indicating that they can provide more accurate diagnoses compared to standard ultrasound alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of breast lesions using Doppler with contrast agents. Martínez, AM., Medina, CJ., Bustos, C., et al.[2020]

The use of a new microbubble contrast agent in ultrasound significantly improved the ability to differentiate between cancerous and benign breast masses, with 100% sensitivity and specificity achieved after its administration.

Increased and prolonged Doppler signal enhancement was observed in cancerous lesions compared to benign ones, indicating that the contrast agent enhances the visualization of vascular features associated with tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbubble contrast agent for color Doppler US: effect on breast masses. Work in progress. Kedar, RP., Cosgrove, D., McCready, VR., et al.[2016]

Contrast-enhanced ultrasound (CEUS) using Sonazoid significantly improved the accuracy of diagnosing focal breast lesions compared to unenhanced ultrasound, with an accuracy rate of 87.2% versus 65.5%.

CEUS also demonstrated higher specificity than both unenhanced ultrasound and contrast-enhanced MRI, while maintaining a low incidence of mild adverse reactions (3.3%), indicating it is a safe and effective diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of sonazoid (perflubutane) for contrast-enhanced ultrasound in the differentiation of focal breast lesions: phase 3 multicenter clinical trial. Miyamoto, Y., Ito, T., Takada, E., et al.[2016]

Contrast-enhanced ultrasound (CEUS) demonstrated high sensitivity (88%) and specificity (82%) in distinguishing between benign and malignant breast lesions, based on a systematic review of 51 studies involving 4875 patients.

CEUS also effectively predicted the pathologic response to neoadjuvant chemotherapy in breast cancer patients, with a sensitivity of 89% and specificity of 83%, indicating its potential as a reliable imaging tool in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Contrast-Enhanced Ultrasound in the Diagnosis and Pathologic Response Prediction in Breast Cancer: A Meta-analysis and Systematic Review. Zhou, SC., Le, J., Zhou, J., et al.[2021]

Micro-bubble contrast agents, specifically perflutren lipid microspheres (Definity), were successfully used to visualize the bile duct in a pig model, allowing for clear imaging down to very small ducts (<2 mm).

This technique could enhance real-time imaging of the biliary system, potentially benefiting procedures like living donor liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of a micro-bubble contrast agent to allow visualization of the biliary tree. Roberts, JP., Neill, A., Goldstein, R.[2016]

In a study of 50 patients with locally advanced breast carcinoma, the use of Levovist contrast medium during color-Doppler ultrasound significantly increased the detection of vascular signals in 94% of lesions, indicating enhanced imaging capabilities.

The enhanced sensitivity of color-Doppler ultrasound with Levovist not only improved the assessment of neoplastic tissue but also correlated with postoperative histopathological findings, making it a valuable tool for evaluating the effectiveness of neoadjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Color-doppler using contrast medium in evaluating the response to neoadjuvant treatment in patients with locally advanced breast carcinoma. Vallone, P., D'Angelo, R., Filice, S., et al.[2005]

In a study of 100 patients with invasive breast cancer, perfusion parameters from contrast-enhanced ultrasonography were found to be significantly higher in estrogen receptor-negative tumors compared to positive ones, indicating a potential link between these parameters and tumor biology.

The study demonstrated that variations in peak intensity of Ki-67, a marker of cell proliferation, were strongly correlated with perfusion parameters, suggesting that these imaging techniques could effectively predict high-grade malignancy and inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography. Masumoto, N., Kadoya, T., Amioka, A., et al.[2017]

In a study of 38 breast masses (22 malignant and 16 benign), the use of the contrast agent Levovist with power Doppler ultrasound (PDUS) and color Doppler ultrasound (CDUS) improved the detection of vascular structures, helping to differentiate between malignant and benign lesions.

Malignant lesions exhibited higher vascularity, with significant parameters identified as Vmax > 15 cm/sec and RI > 0.80 for CDUS, and RI > 0.70 for PDUS, indicating that these measurements can aid in reducing unnecessary surgeries by accurately identifying cancerous masses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Contrast enhanced power Doppler and color Doppler ultrasound in breast masses: Efficiency in diagnosis and contributions to differential diagnosis]. Algül, A., Balci, P., Seçil, M., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7735954/

Contrast-Enhanced Ultrasound Imaging of Breast Masses This pilot study evaluated use of contrast-enhanced ultrasound (CEUS) to reduce the number of benign breast masses recommended for biopsy.

2. withpower.com withpower.com/trial/phase-1-breast-neoplasms-10-2020-de7c1

Contrast-Enhanced Ultrasound for Identifying Breast Masses This clinical trial investigates the role of contrast enhanced ultrasound (CEUS) in identifying cystic breast masses as benign or malignant.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/jum.14917

Contrast‐Enhanced Ultrasound Imaging of Breast Masses ... This pilot study evaluated use of contrast-enhanced ultrasound (CEUS) to reduce the number of benign breast masses recommended for biopsy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7710668/

Accuracy of Contrast-Enhanced Ultrasound Compared ... This pilot study compared contrast enhanced ultrasound (US) with contrast-enhanced magnetic resonance imaging (MRI) in assessing the treatment response in ...

5. definityimaging.com definityimaging.com/

DEFINITY® (Perflutren Lipid Microsphere) Diagnostic ... DEFINITY is a diagnostic ultrasound enhancing agent that uses advanced microbubble technology to opacify the left ventricular chamber.

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

Definity - accessdata.fda.gov Perflutren lipid microspheres exhibit lower acoustic impedance than blood and enhance the intrinsic backscatter of blood. These physical acoustic properties of ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/perflutren-lipid-microsphere-intravenous-route/description/drg-20067608

Perflutren lipid microsphere (intravenous route) Unlike x-rays, ultrasound does not involve ionizing radiation. The lipid microspheres sonicated preparation contains very small gas-filled lipid ...

8. openaccessjournals.com openaccessjournals.com/articles/perflutren-lipid-microsphere-injectable-suspension-for-cardiac-ultrasound.pdf

Perflutren lipid microsphere injectable suspension for cardiac ... Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images.

9. drugs.com drugs.com/mtm/perflutren.html

Perflutren Uses, Side Effects & Warnings Perflutren works by changing the way ultrasound waves travel within your heart. This helps the ultrasound portray a sharper image of your heart.