Contrast-Enhanced Ultrasound for Breast Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Kibo Nam, PhD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

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

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This phase II/III trial studies if contrast-enhanced ultrasounds using a contrast dye, perflutren lipid microspheres (Definity), can predict the response to chemotherapy by estimating the pressure in the cancer in patients with breast cancer that has spread to nearby tissues and lymph nodes (locally advanced). The efficacy of cancer therapy is affected by the pressure in the cancer. Definity is a contrast dye used to create better images during ultrasounds. The purpose of this trial is to determine if a special kind of ultrasound, called contrast-enhanced ultrasound, an experimental imaging test, can detect pressures in cancer to determine the response to neoadjuvant chemotherapy in patients with breast cancer.

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 data supports the effectiveness of the treatment Perflutren Lipid Microspheres, Definity, Definity RT for breast cancer?

The research does not provide direct evidence for the effectiveness of Perflutren Lipid Microspheres, Definity, or Definity RT in treating breast cancer, but it does highlight the use of similar contrast agents like perflubutane in enhancing ultrasound imaging to differentiate between benign and malignant breast lesions. ^{1 2 3 4 5}

Is contrast-enhanced ultrasound using Definity safe for humans?

Definity, a contrast agent used in ultrasound, has been associated with some serious heart and lung reactions, including a few deaths, but these are rare. Most studies show that severe adverse reactions are uncommon, and the use of Definity does not significantly increase the risk of severe events compared to not using it. ^{6 7 8 9 10}

How is contrast-enhanced ultrasound different from other breast cancer treatments?

Contrast-enhanced ultrasound (CEUS) for breast cancer is unique because it uses a special contrast agent, like perflubutane, to improve the imaging of breast tissue, helping to differentiate between benign and malignant lesions. Unlike traditional treatments, CEUS is primarily a diagnostic tool that enhances ultrasound images to assess tumor characteristics and predict responses to therapies, rather than directly treating the cancer itself. ^{1 2 4 11 12}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Perflutren Lipid Microspheres (Contrast Agent)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic Rochester, MN

Thomas Jefferson University Hospital Philadelphia, PA

UT Southwestern/Simmons Cancer Center-Dallas Dallas, TX

Who Is Running the Clinical Trial?

Kibo Nam Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. United States 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. [2016] The objective of our study was to compare the efficacy of contrast-enhanced ultrasound (CEUS) using the ultrasound contrast agent Sonazoid (perflubutane) with unenhanced ultrasound and supplementary contrast-enhanced MRI in the differential diagnosis (benign vs malignant) of focal breast lesions. The safety of Sonazoid was also assessed in this study.

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography. [2017] Whether the contrast effects of perflubutane on contrast-enhanced ultrasonography can predict the malignancy grade of breast cancer is unknown. We analyzed associations between perfusion parameters created from time-intensity curves based on enhancement intensity and temporal changes in contrast-enhanced ultrasonography and clinicopathologic factors in 100 consecutive patients with invasive breast cancer. Values of perfusion parameters were significantly greater in estrogen receptor-negative than -positive tumors (peak intensity, p = 0.0002; ascending slope, p = 0.006; area under the curve, p = 0.0006). Variations in the peak intensity of Ki-67 were significantly correlated in all tumors (r = 0.54, p

3. Japan pubmed.ncbi.nlm.nih.gov

Impact of parametric imaging on contrast-enhanced ultrasound of breast cancer. [2019] To prospectively evaluate the usefulness of contrast-enhanced ultrasound (CEUS) using parametric imaging for breast cancer in a multicenter study.

4. United States 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. [2021] To determine the overall performance of contrast-enhanced ultrasound (CEUS) in differentiating between benign and malignant breast lesions and in predicting the pathologic response to neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC).

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

The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55). [2022] Tumour xenografts of well-discernible sizes can be examined well by molecular ultrasound. Here, we investigated whether very early breast carcinomas express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging with targeted microbubbles.

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

Safety of ultrasound contrast agents in stress echocardiography. [2015] Definity and Optison are perflutren-based ultrasound contrast agents used in echocardiography. United States Food and Drug Administration warnings regarding serious cardiopulmonary reactions and death after Definity administration highlighted the limited safety data in patients who undergo contrast stress echocardiography. From 1998 and 2007, 2,022 patients underwent dobutamine stress echocardiography and 2,764 underwent exercise stress echocardiography with contrast at the Cleveland Clinic. The echocardiographic database, patient records, and the Social Security Death Index were reviewed for the timing and cause of death, severe adverse events, arrhythmias, and symptoms. Complication rates for contrast dobutamine stress echocardiography and exercise stress echocardiography were compared with those in a control group of 5,012 patients matched for test year and type who did not receive contrast. Ninety-five percent of studies were performed in outpatients. There were no differences in the rates of severe adverse events (0.19% vs 0.17%, p = 0.7), death within 24 hours (0% vs 0.04%, p = 0.1), cardiac arrest (0.04% vs 0.04%, p = 0.96), and sustained ventricular tachycardia (0.2% vs 0.1%, p = 0.32) between patients receiving and not receiving intravenous contrast, respectively. In conclusion, severe adverse reactions to intravenous contrast agents during stress echocardiography are uncommon. Contrast use does not add to the baseline risk for severe adverse events in patients who undergo stress echocardiography.

7. England pubmed.ncbi.nlm.nih.gov

Ultrasound contrast agents: balancing safety versus efficacy. [2022] In October, 2007, the FDA issued a new 'black box' warning, several new disease state contraindications and a mandated 30-min post-procedure monitoring period for the ultrasound contrast agents Definity (perflutren lipid microsphere injectable suspension, Lantheus Medical Imaging, North Billerica, MA, USA) and Optison (perflutren protein type A microspheres for injectable suspension, GE Healthcare, Buckinghamshire, UK). These labeling changes were largely secondary to reports of 4 patient deaths, and approximately 190 other 'serious cardiopulmonary reactions' that were temporally related but not clearly causally attributable to Definity administration. Contrast agent use in the US plummeted in the immediate aftermath of this FDA action, with many hospitals, physician offices and outpatient imaging centers suspending contrast echocardiography altogether. This review will focus on the immediate response from the international physician community, new contrast agent safety data published within the past year, results of a special meeting of the FDA Cardio-Renal panel devoted to contrast agent safety in June 2008, recently issued revised product labeling for both agents and future prospects for contrast echocardiography.

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

Sudden death after intravenous administration of a perflutren contrast agent: a case of pseudocomplication? [2014] Perflutren cardiac ultrasound agents improve diagnostic accuracy in patients whose imaging is technically difficult. This report describes a case of sudden death approximately 5 minutes after the intravenous administration of 0.5 mL of perflutren contrast agent (Definity) during transthoracic echocardiography with suboptimal baseline images performed 10 days after coronary artery bypass graft surgery because of hypotension and tachycardia in a 73-year-old patient with severe left ventricular systolic dysfunction. Autopsy did not reveal a clear direct relationship between perflutren and death. This is the first reported case of death related temporally to an echocardiographic contrast agent occurring in Canada and could represent a case of pseudocomplication.

9. Australia pubmed.ncbi.nlm.nih.gov

Contrast echocardiography in Australian clinical practice. [2022] The second-generation contrast agent Definity (a perflutren microsphere) became available in Australia in mid-2007. We describe the introduction of contrast echocardiography into a high-volume quaternary teaching hospital, performing over 16,000 echocardiograms per year. Workflow protocols were developed for patient selection, contrast administration, and image acquisition and analysis.

10. United States 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. [2022] Definity (perflutren lipid microsphere) is an ultrasound contrast agent approved for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. This prospective, open-label, nonrandomized, multicenter, phase 4 surveillance registry study was conducted at 15 clinical sites in the United States and was designed to assess the risk for adverse cardiopulmonary events occurring during or within the initial 30 min after Definity administration in routine clinical practice.

11. South Africa pubmed.ncbi.nlm.nih.gov

A contrast-enhanced ultrasound study of benign and malignant breast tissue. [2016] To determine the diagnostic value of haemodynamic contrast-enhanced ultrasound assessment in benign and malignant breast tissue, using histological examination as the reference standard.

12. Germany pubmed.ncbi.nlm.nih.gov

[Ultrasound contrast media--principles and clinical applications]. [2022] This article reviews the technical basics and the application of contrast-enhanced ultrasonography. Ultrasound contrast agents have been evaluated in various organs and have proven to be particularly useful in the detection and characterization of liver lesions. Experiences in small parts (such as breast, or lymph nodes) are so far limited, because only since recently are the technical prerequisites available for contrast-enhanced ultrasound high-frequency transducers. Ultrasound contrast media can be used for functional studies, e. g., of organ or tumor perfusion. Mathematical models were primarily developed for measuring myocardial perfusion and have recently been adapted for studying tumors. In animal experiments as well as in clinical applications, quantitative parameters of tumor perfusion have been evaluated as surrogate parameters for response to radiotherapy, chemotherapy, or treatment with anti-angiogenic agents.