CEUS to Predict Treatment Response in Breast Cancer

Overseen By Rebecca Jordan, M.A.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Milton S. Hershey Medical Center

Must be taking: ICI therapy

Disqualifiers: Pregnancy, Egg allergy, PEG allergy

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: 8-12 weeks

20 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 quickly indicate the effectiveness of a treatment for triple-negative breast cancer (TNBC). The treatment uses Lumason, a contrast agent, to enhance ultrasound images. The goal is to assess whether CEUS can detect treatment responses earlier than standard scans like MRIs or CTs. Suitable participants are those diagnosed with TNBC who plan to begin a specific combined immunotherapy treatment. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to experience this innovative approach.

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 prior data suggests that contrast enhanced ultrasound is safe for predicting treatment response in breast cancer?

Research shows that Lumason, used in contrast-enhanced ultrasound (CEUS), is generally safe for patients. Studies have found a very low death rate of 0.03% for patients receiving Lumason, which is lower than for those who did not receive it.

Other studies found no harmful effects in animal tests, indicating a positive sign for human safety. Lumason's approval for use in other medical imaging tests further supports confidence in its safety.

Overall, evidence suggests that Lumason is well-tolerated with minimal risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Contrast Enhanced Ultrasound (CEUS) with Lumason for breast cancer because it offers a unique way to predict treatment response. Unlike standard treatments like chemotherapy or surgery, which directly target the cancer itself, this technique focuses on enhancing imaging to assess how well a tumor is responding to treatment. Lumason is a special contrast agent that helps create clearer ultrasound images, allowing doctors to see detailed changes in blood flow within the tumor. This could potentially lead to more personalized treatment plans and faster adjustments in therapy, offering a promising step forward in breast cancer care.

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

Research has shown that contrast-enhanced ultrasound (CEUS) with Lumason, which participants in this trial will receive, can predict the effectiveness of breast cancer treatments early. This method detects changes in cancer tissues sooner than other imaging techniques like MRI or CT scans. CEUS uses a special contrast agent to clarify ultrasound images, aiding in treatment assessment. This is particularly beneficial for patients with triple negative breast cancer (TNBC), where early treatment adjustments are crucial. Although research continues, early findings suggest that CEUS could be a valuable tool for managing and tracking breast cancer treatment progress. ^{6 7 8 9 10}

Who Is on the Research Team?

Seth Hardy, M.D.

Principal Investigator

Assistant Professor - Department of Radiology, Penn State Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lumason

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Contrast-enhanced ultrasound (CEUS) can effectively monitor the efficacy of neoadjuvant chemotherapy in breast cancer, showing significant changes in tumor microcirculation indicators and CEUS parameters after treatment in an animal model.

In particular, CEUS parameters like maximum intensity (IMAX) and time to peak (TTP) correlated with biological indicators such as micro vessel density (MVD) and vascular endothelial growth factor receptors (VEGFR), suggesting that CEUS could serve as an early predictor of chemotherapy effectiveness.

NCBI (Pubmed)

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. Zhou, SC., Le, J., Fan, YW., et al.[2017]

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]

In a study of 75 invasive breast cancers using contrast-enhanced ultrasound (CEUS), significant correlations were found between CEUS kinetic parameters and traditional prognostic factors, such as tumor grade and axillary lymph node status.

Tumors that showed earlier peak enhancement and faster wash-out of the contrast agent were linked to poorer prognostic indicators, suggesting that CEUS could be a valuable tool in assessing breast cancer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of contrast-enhanced ultrasound kinetics with prognostic factors in invasive breast cancer. Szabó, BK., Saracco, A., Tánczos, E., et al.[2021]

PSMA-targeted nanobubbles (NBs) combined with low-frequency therapeutic ultrasound (TUS) significantly increased cancer cell apoptosis in PSMA-expressing tumors, achieving an impressive 78.45% apoptosis rate compared to control groups.

In vivo studies in mice and rabbits showed that this targeted nanobubble therapy (TNT) not only inhibited tumor growth but also improved overall survival by 103%, indicating its potential as an effective treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-mediated drug-free theranostics for treatment of prostate cancer. Perera, RH., Berg, FM., Abenojar, EC., 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]

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]

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]

In a study of 30 patients with locally advanced breast cancer, contrast-enhanced ultrasound (CEUS) showed that changes in quantitative parameters like peak enhancement (PE), time-to-peak (TTP), and mean transit time (MTT) can effectively predict responses to neoadjuvant chemotherapy (NACT).

Responders to NACT exhibited significant changes in CEUS parameters after each treatment cycle, with TTP showing a diagnostic accuracy of 87.2% after the third cycle, suggesting that CEUS could help tailor chemotherapy regimens and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast enhanced ultrasound quantitative parameters for assessing neoadjuvant chemotherapy response in patients with locally advanced breast cancer. Sharma, A., Grover, SB., Mani, C., et al.[2022]

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]

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/early-phase-1-breast-neoplasms-7-2023-571cb

CEUS to Predict 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 ...

3. journals.lww.com journals.lww.com/prsgo/fulltext/2024/07000/randomized_feasibility_study_evaluating_multiple.45.aspx

Randomized Feasibility Study Evaluating Multiple... A small randomized study demonstrates that lymphatic channels can be visualized in the extremities with two additional commercially available microbubbles.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09541

Contrast-Enhanced Ultrasound and Shear Wave ... ARM I: Patients receive sulfur hexafluoride lipid microspheres (Lumason) intradermally on the healthy arm and undergo CEUS imaging over 30 minutes during ...

5. mdpi.com mdpi.com/1422-0067/24/6/5474

Enhancing Targeted Therapy in Breast Cancer by ... In this review, we will discuss the current classification and standard of care for breast cancer, the application of nanomedicine, and ultrasound-responsive ...

6. lumason.com lumason.com/safety/

Safety Patients who received LUMASON UEA had a mortality rate of only 0.03%—lower than in those who didn't receive a UEA. Among patients who received UEAs, ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/203684s009lbl.pdf

Lumason - accessdata.fda.gov No adverse developmental outcomes were observed in animal reproduction studies with administration of sulfur hexafluoride lipid-type A microspheres in pregnant ...

8. lumason.com lumason.com/

LUMASON Home Page - LUMASON LUMASON (sulfur hexafluoride lipid-type A microspheres) for injectable suspension, for intravenous use or intravesical use is an ultrasound contrast agent.

9. mayoclinic.org mayoclinic.org/drugs-supplements/sulfur-hexafluoride-lipid-type-a-microspheres-injection-route-intravenous-route/description/drg-20405988

Sulfur hexafluoride lipid type a microspheres (injection ... Safety and efficacy have been established. Geriatric. Appropriate studies performed to date have not demonstrated geriatric-specific problems ...

10. fda.gov fda.gov/files/drugs/published/60_203684-sulfur-hexafluoride-clinical-prea.pdf

division of medical imaging products administration of Lumason (sulfur hexafluoride lipid-type A microspheres) as an ultrasound ... efficacy and safety data on the use of Lumason ...