CEUS to Predict Treatment Response in Breast Cancer

Overseen by Seth Hardy, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Milton S. Hershey Medical Center

Must be taking: ICI therapy

Disqualifiers: Pregnancy, Egg allergy, PEG allergy

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing whether a special type of ultrasound called contrast enhanced ultrasound (CEUS) can show if patients with aggressive breast cancer are responding to treatment faster than traditional scans. The target group is patients with triple negative breast cancer who are receiving a combination of immune therapies. CEUS uses a special dye to make the images clearer, helping doctors see changes in the tumor more quickly.

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

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Lumason in predicting treatment response in breast cancer?

Research shows that contrast-enhanced ultrasound (CEUS), which uses agents like Lumason, can help predict early response to chemotherapy in breast cancer by showing changes in blood flow within tumors. This method has been effective in distinguishing between patients who respond to treatment and those who do not. ^{1 2 3 4 5}

Is the use of sulfur hexafluoride lipid-type A microspheres generally safe in humans?

Research on sulfur hexafluoride-filled microbubbles, used as ultrasound contrast agents, suggests they are generally safe, with studies focusing on their use in imaging and drug delivery. These microbubbles have been evaluated for their effects on liver tumors and thrombi, showing potential for safe use in humans. ^{6 7 8 9 10}

How does CEUS differ from other treatments for breast cancer?

Contrast-enhanced ultrasound (CEUS) is unique because it uses microbubbles to enhance ultrasound images, allowing doctors to see how blood flows through breast cancer tumors in real-time. This method helps predict early responses to chemotherapy, which is different from traditional imaging techniques that may not provide such detailed information about blood flow and tumor response. ^{1 3 11 12 13}

Research Team

Seth Hardy, M.D.

Principal Investigator

Assistant Professor - Department of Radiology, Penn State Health

Eligibility Criteria

This trial is for adults over 18 with Stage I-III Triple Negative Breast Cancer (TNBC) or stage IV TNBC who still have the primary breast tumor. They must be willing to follow study procedures and receive combined Immune Checkpoint Inhibitors therapy as standard care. Pregnant women, those allergic to eggs, or with past reactions to ultrasound contrast agents like PEG can't participate.

Inclusion Criteria

My doctor plans to treat my cancer with combined immune checkpoint inhibitors.

I am willing and able to sign the consent form for this study.

I am willing and able to follow all study rules and visit schedules.

Exclusion Criteria

Other clinical trials are not excluded but participation must be cleared with the other clinical trial PIs

I am not pregnant, allergic to eggs, or have had reactions to ultrasound contrast.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combined chemotherapy and immune checkpoint inhibitors (ICI) for triple negative breast cancer (TNBC)

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lumason (Contrast Agent)

Trial Overview The study is testing if Contrast Enhanced Ultrasound (CEUS), using a contrast agent called Lumason, can predict how well TNBC patients respond to chemotherapy and immune checkpoint inhibitors sooner than current methods like MR or CT scans.

Participant Groups

Group I: Contrast Enhanced Ultrasound (with Lumason) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Dr. Robert Harbaugh

Milton S. Hershey Medical Center

Chief Medical Officer since 2024

MD from Penn State College of Medicine

Don McKenna

Milton S. Hershey Medical Center

Chief Executive Officer since 2024

Master’s in Public Administration and Bachelor of Science in Business Administration and Marketing from Long Island University

Findings from Research

In a study of 19 patients with invasive breast cancer, real-time harmonic contrast-enhanced ultrasound (CEUS) was able to predict early response to neoadjuvant chemotherapy by measuring the time-to-peak (tp) of contrast agent flow, showing significant differences between responders and non-responders.

Responders to chemotherapy exhibited a significantly longer tp at week 5 compared to baseline, indicating that slower intravascular contrast flow in tumors may serve as an effective early response evaluation method, although further research with larger populations is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy. Saracco, A., Szabó, BK., Tánczos, E., et al.[2018]

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]

A study involving 53 patients with various advanced solid tumors established a safe premedication protocol for paclitaxel liposome (Lipusu), which included methylprednisolone and granisetron to minimize side effects.

The recommended premedication regimen effectively reduced toxicity without any treatment-related deaths, highlighting its safety and potential for improving patient comfort during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study on the premedication of paclitaxel liposome in the treatment of solid tumors. Zhang, Q., Huang, XE., Gao, LL.[2015]

A new method for radiolabeling microbubbles allows for effective tracking of their behavior in the body, which is crucial for improving drug delivery using microbubble-enabled focused ultrasound (MB-FUS).

Studies showed that the composition of microbubbles affects their dissolution rates and how well they deliver drugs to tumors, with findings suggesting that microbubble design can significantly enhance treatment efficacy and safety in nanomedicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Pharmacokinetics Reveal Impact of Lipid Composition on Microbubble and Nanoprogeny Shell Fate. Rajora, MA., Dhaliwal, A., Zheng, M., et al.[2023]

Intravenous injection of lipid-coated microbubbles (LCMs) significantly enhances the echogenicity of malignant liver tumors in a study involving 16 rats, demonstrating a clear difference in imaging quality compared to a saline control.

The increased echogenicity, measured by signal-to-noise ratio, lasted for 30 minutes post-injection, and histological analysis confirmed that LCMs selectively accumulated in the tumor tissue, suggesting a potential mechanism for improved imaging of liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of experimental rat liver tumors by contrast-assisted ultrasonography. D'Arrigo, JS., Ho, SY., Simon, RH.[2019]

The study developed new microbubbles using lipids and sulfur hexafluoride (SF6) that significantly enhance the echogenicity of thrombi, improving their visibility during ultrasound imaging.

These targeted microbubbles demonstrated high stability and maintained their characteristics for up to 8 hours, providing a longer diagnostic window compared to traditional nontargeted microbubbles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonging the ultrasound signal enhancement from thrombi using targeted microbubbles based on sulfur-hexafluoride-filled gas. Wang, B., Zang, WJ., Wang, M., et al.[2016]

Covalently linking poly(lactic-co-glycolic acid) nanoparticles to ultrasound-activated microbubbles significantly enhances their delivery to tumors, achieving a 16% delivery rate per gram of tissue, which is 5 to 57 times greater than control methods.

Using this composite-agent formulation to deliver 5-fluorouracil (5FU) resulted in a 67% reduction in tumor volume and improved survival rates in mice with C6 gliomas, indicating a promising approach for treating tumors resistant to traditional intravenous 5FU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-activated agents comprised of 5FU-bearing nanoparticles bonded to microbubbles inhibit solid tumor growth and improve survival. Burke, CW., Alexander, E., Timbie, K., et al.[2021]

In a study of 51 patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy, quantitative parameters from contrast-enhanced ultrasound (CEUS) were found to be strong predictors of pathological complete response (pCR), with a sensitivity of 93.7% and specificity of 80.0%.

CEUS parameters, such as PEAK and TTP%, outperformed tumor diameter measurements in predicting pCR, indicating that CEUS can serve as a more effective functional technique for evaluating tumor response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy. Wan, CF., Liu, XS., Wang, L., et al.[2019]

Microbubble contrast-enhanced ultrasonography (CEUS) is a promising imaging technique for assessing changes in tumor blood vessels after antiangiogenic cancer treatments, offering advantages over traditional imaging methods.

CEUS has shown comparable effectiveness to dynamic contrast-enhanced MRI and PET scans in differentiating between cancerous and normal tissues, and it may enhance cancer diagnosis and treatment response evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonographic assessment of tumor response: from in vivo models to clinical applications. Hwang, M., Niermann, KJ., Lyshchik, A., et al.[2016]

References

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

Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy. [2018]

2. 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]

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

Contrast enhanced ultrasound quantitative parameters for assessing neoadjuvant chemotherapy response in patients with locally advanced breast cancer. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Correlation of contrast-enhanced ultrasound kinetics with prognostic factors in invasive breast cancer. [2021]

5. Pakistan pubmed.ncbi.nlm.nih.gov

Study on breast cancer animal model of tumor-micro vessel variation before and after the chemotherapy by contrast enhanced ultrasound quantitative analysis. [2017]

6. France pubmed.ncbi.nlm.nih.gov

A clinical study on the premedication of paclitaxel liposome in the treatment of solid tumors. [2015]

7. Germany pubmed.ncbi.nlm.nih.gov

Quantitative Pharmacokinetics Reveal Impact of Lipid Composition on Microbubble and Nanoprogeny Shell Fate. [2023]

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

Ultrasound-mediated drug-free theranostics for treatment of prostate cancer. [2023]

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

Detection of experimental rat liver tumors by contrast-assisted ultrasonography. [2019]

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

Prolonging the ultrasound signal enhancement from thrombi using targeted microbubbles based on sulfur-hexafluoride-filled gas. [2016]

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

Ultrasound-activated agents comprised of 5FU-bearing nanoparticles bonded to microbubbles inhibit solid tumor growth and improve survival. [2021]

12. Ireland pubmed.ncbi.nlm.nih.gov

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy. [2019]

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

Sonographic assessment of tumor response: from in vivo models to clinical applications. [2016]