Contrast-Enhanced Ultrasound for Breast Cancer

Recruiting at 2 trial locations

Overseen By Kibo Nam, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: Kibo Nam

Must be taking: Neoadjuvant chemotherapy

Must not be taking: Endocrine therapy

Disqualifiers: Males, Metastatic disease, Unstable health, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: 1

Duration: Varies with NAC schedule

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a special kind of ultrasound to determine if it can predict chemotherapy effectiveness for certain breast cancer patients. Researchers use a contrast dye called Definity (also known as Perflutren Lipid Microspheres) to enhance ultrasound images. They aim to discover if this enhanced imaging can measure pressure in cancer cells to guide treatment decisions. Women with breast cancer that has spread to nearby tissues and who are about to start chemotherapy might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that contrast-enhanced ultrasound is safe for breast cancer patients?

Research has shown that perflutren lipid microspheres, known as Definity, are generally safe. Definity enhances the clarity of ultrasound images and has FDA approval for other uses, indicating it has passed safety checks for those purposes. Studies using similar technology, such as MRgFUS-MB for breast cancer, reported no major side effects, suggesting the treatment is well-tolerated. Therefore, the safety information appears promising for potential participants in this study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about contrast-enhanced ultrasound (CEUS) with perflutren lipid microspheres for breast cancer because it offers a new way to visualize and track tumors. Unlike standard imaging techniques, like mammography or MRI, CEUS provides real-time, enhanced imaging of blood flow in tumors without the use of ionizing radiation. This could lead to earlier and more accurate assessments of how well a tumor is responding to treatment. Plus, the use of perflutren lipid microspheres makes the procedure minimally invasive, as it only requires a simple intravenous injection. This could make monitoring breast cancer treatment more accessible and comfortable for patients.

What evidence suggests that contrast-enhanced ultrasound is effective for predicting chemotherapy response in breast cancer?

This trial will evaluate the use of contrast-enhanced ultrasound (CEUS) with perflutren lipid microspheres, known as Definity, for breast cancer imaging. Studies have shown that CEUS significantly improves breast cancer imaging, surpassing regular ultrasounds in distinguishing between benign (non-cancerous) and malignant (cancerous) breast lumps. Research suggests that this technology could also enhance imaging of the lymphatic system, potentially leading to better surgical outcomes. Definity uses tiny bubbles to clarify ultrasound images, making it a promising tool for predicting chemotherapy effectiveness by estimating tumor pressure. Participants in this trial will undergo CEUS and receive perflutren lipid microspheres as part of the diagnostic process. ^{3 6 7 8 9}

Who Is on the Research Team?

Kibo Nam, PhD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for adults over 21 with locally advanced breast cancer, scheduled for neoadjuvant chemotherapy, and willing to follow study procedures. It's not for those with other primary cancers, distal metastatic disease, pregnant or nursing women, or individuals with certain heart conditions, recent surgery, unstable cardiopulmonary issues, or allergies to Definity.

Inclusion Criteria

I am scheduled for chemotherapy before surgery.

I am a woman who can have children and my pregnancy test is negative.

Provide signed and dated informed consent form

Exclusion Criteria

I do not have serious heart rhythm problems.

I have severe lung problems like emphysema or blood clots in my lungs.

I do not have severe heart failure that limits my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo unenhanced baseline ultrasound imaging before NAC

1 week

1 visit (in-person)

Treatment

Participants receive neoadjuvant chemotherapy (NAC) and undergo contrast-enhanced ultrasound (CEUS) with perflutren lipid microspheres at multiple time points

Varies with NAC schedule

Multiple visits (in-person) for CEUS and NAC

Follow-up

Participants are monitored for safety and effectiveness after completion of NAC

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Perflutren Lipid Microspheres

Trial Overview The trial tests if contrast-enhanced ultrasounds using Definity can predict chemotherapy response by measuring pressure in the tumor. This phase II/III trial aims to improve imaging techniques during treatment of locally advanced breast cancer.

How Is the Trial Designed?

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

Patients undergo CEUS and receive perflutren lipid microspheres IV over 10-15 minutes before NAC, after 10% of NAC, and after 30% of NAC. Patients also undergo unenhanced baseline ultrasound imaging before NAC, after 10% of NAC, after 30% of NAC, and after 100% of NAC

Who Is Running the Clinical Trial?

Kibo Nam

Lead Sponsor

Trials

1

Recruited

200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 4,786 patients undergoing stress echocardiography, the use of perflutren-based contrast agents like Definity and Optison did not increase the risk of severe adverse events compared to patients who did not receive contrast.

The rates of serious complications, including death within 24 hours and cardiac arrest, were similar between those receiving contrast and those who did not, indicating that the use of these contrast agents is generally safe in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents in stress echocardiography. Gabriel, RS., Smyth, YM., Menon, V., et al.[2015]

In a study involving 1,060 patients, Definity (perflutren lipid microsphere) was found to be well tolerated, with no deaths or serious adverse events reported during or within 30 minutes after administration.

The overall adverse event rate was 10.8%, with a low drug-related adverse event rate of 3.5%, indicating that most adverse events were mild or moderate, making Definity a safe option for patients with suboptimal echocardiograms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. Weiss, RJ., Ahmad, M., Villanueva, F., et al.[2022]

In a study involving 65 breast cancer patients, parametric imaging in contrast-enhanced ultrasound (CEUS) significantly improved the visibility of tumors compared to standard imaging methods, with the best average ranking for parametric images.

The maximal tumor diameter measured by CEUS showed a strong correlation with pathological findings, indicating that CEUS can be a reliable tool for assessing tumor size in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of parametric imaging on contrast-enhanced ultrasound of breast cancer. Noro, A., Nakamura, T., Hirai, T., et al.[2019]

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]

Contrast-enhanced ultrasonography is particularly effective for detecting and characterizing liver lesions, showcasing its utility in clinical settings.

Recent advancements in high-frequency transducers have expanded the application of ultrasound contrast agents to functional studies of organ and tumor perfusion, providing valuable insights into treatment responses in both animal and clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ultrasound contrast media--principles and clinical applications]. Delorme, S., Krix, M., Albrecht, T.[2022]

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]

Molecular ultrasound using VEGFR2-targeted microbubbles (BR55) is effective for imaging very early breast carcinomas, particularly in small lesions (2 mm in diameter), where the binding of microbubbles is highest.

As tumors grow larger, the expression of VEGFR2 decreases, but the imaging technique remains reliable, indicating its potential for detecting and characterizing small breast lesions based on angiogenic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55). Bzyl, J., Palmowski, M., Rix, A., et al.[2022]

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]

Haemodynamic contrast-enhanced ultrasound assessment demonstrated a high diagnostic sensitivity of 97% and specificity of 80% in distinguishing between benign and malignant breast lesions, based on a study of 50 patients.

Key metrics such as area under the curve (AUC) and peak enhancement (PE) were significant indicators of malignancy, suggesting that this ultrasound technique can effectively aid in breast cancer diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contrast-enhanced ultrasound study of benign and malignant breast tissue. Barnard, S., Leen, E., Cooke, T., et al.[2016]

In response to serious safety concerns, including 4 patient deaths and 190 serious reactions, the FDA issued a 'black box' warning for ultrasound contrast agents Definity and Optison, leading to a significant decline in their use in the US.

Recent safety data and discussions from the FDA Cardio-Renal panel indicate ongoing evaluation of these agents, with revised labeling aimed at improving safety protocols for contrast echocardiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound contrast agents: balancing safety versus efficacy. Main, ML., Goldman, JH., Grayburn, PA.[2022]

A 73-year-old patient experienced sudden death shortly after receiving a perflutren contrast agent during an echocardiogram, highlighting potential risks associated with its use in patients with severe heart conditions.

Despite the timing of the death, autopsy results did not establish a direct link between the perflutren agent and the fatal event, suggesting that this case may represent a pseudocomplication rather than a direct adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden death after intravenous administration of a perflutren contrast agent: a case of pseudocomplication? Mahjoub, H., Roméo, P., Leung, TK., et al.[2014]

In the first year of using the second-generation contrast agent Definity in echocardiography, 161 patients showed a significant improvement in endocardial definition scores (p=0.0001), enhancing the clarity of heart imaging.

The use of contrast echocardiography led to the detection of clinically significant conditions that were missed in standard 2D imaging, with a very low adverse event rate of only 0.6%, indicating its safety and efficacy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast echocardiography in Australian clinical practice. Hamilton-Craig, C., Boga, T., West, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04721886

Contrast-Enhanced Ultrasound Scan for the Estimation of ... This clinical trial studies the use of contrast-enhanced ultrasound (CEUS) in estimating tissue pressure in patients with breast cancer. Diagnostic procedures, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24660739/

Efficacy of Sonazoid (Perflubutane) for Contrast-Enhanced ... CEUS using Sonazoid was confirmed to be superior to unenhanced ultrasound for the differential diagnosis (benign vs malignant) of focal breast lesions.

3. f.oaes.cc f.oaes.cc/xmlpdf/a87f04ed-c3f6-4d33-b426-14bce8b36696/par40145_down.pdf?v=50

Contrast-enhanced ultrasound for lymphatic mapping This review suggests that CEUS technology holds significant potential for advancing lymphatic imaging and improving surgical outcomes in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06171607

Contrast Enhanced Ultrasound Medical Imaging for ... This clinical trial investigates the role of contrast enhanced ultrasound (CEUS) in identifying cystic breast masses as benign or malignant. Ultrasound is a ...

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 The DEFINITY RT vial contains components that upon activation and dilution yield perflutren lipid microspheres. The unactivated vial contains a colorless ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5493049/

Ultrasound Molecular Imaging With BR55 in Patients With ... At 13 minutes after MBKDR injection, 23 (96%) of 24 ovarian and breast cancers could be seen on USMI (10 of 10 ovarian cancers and 13 of 14 ...

8. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00650-9/fulltext

Radiation enhancement using focussed ultrasound ... This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0167814024006509

Radiation enhancement using focussed ultrasound ... In our recently completed clinical trial for breast malignancies, we observed no relevant adverse events and noted encouraging tumour responses with MRgFUS-MB ...