Contrast-Enhanced Ultrasound for Liver Cancer

Overseen By John Eisenbrey, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: john eisenbrey

Disqualifiers: Medically unstable, Terminally ill, others

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: During TACE procedure

266 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special ultrasound using a contrast agent can quickly and accurately assess the effectiveness of a liver cancer treatment called transarterial chemoembolization (TACE). TACE targets liver tumors with a combination of a blocking agent and chemotherapy. The trial will compare this ultrasound method to standard imaging tests like MRI or CT scans, which are typically performed later. Individuals scheduled for TACE for a liver tumor and who are medically stable might be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to potentially groundbreaking advancements in liver cancer treatment.

Will I have to stop taking my current medications?

The trial information 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 assessing liver cancer treatment response?

Research has shown that using Lumason, a special type of contrast agent, in liver ultrasound scans is generally safe. Studies have found that the death rate for patients who received Lumason is very low, at just 0.03%, which is even lower than for those who did not use these contrast agents.

However, some reports have noted serious side effects, such as heart and lung issues, when using these agents. Although rare, these serious reactions can occur during or immediately after the injection. While most people tolerate the treatment well, a small risk of serious side effects exists. Participants should discuss these risks with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using contrast-enhanced ultrasound (CEUS) for liver cancer because it offers a new way to improve the precision of existing treatments. Unlike standard imaging methods, CEUS provides real-time, detailed images by using a contrast agent called Lumason. This helps doctors better visualize the liver and assess the effectiveness of transarterial chemoembolization (TACE), a common treatment for liver cancer. By improving the accuracy of TACE, CEUS could lead to better treatment outcomes and potentially fewer side effects for patients.

What evidence suggests that contrast-enhanced ultrasound is effective for assessing treatment response in liver cancer?

Research has shown that contrast-enhanced ultrasound (CEUS) with Lumason, a special dye, holds promise for liver imaging. Studies have found that CEUS produces clear images of blood flow in the liver, crucial for diagnosing liver diseases. In this trial, participants will receive Lumason and undergo CEUS at various stages, including during treatments like transarterial chemoembolization (TACE). This approach enables doctors to assess treatment effectiveness sooner than traditional imaging methods. Overall, CEUS may provide a faster and more cost-effective way to monitor liver cancer treatment. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with liver tumors who are undergoing a treatment called transarterial chemoembolization (TACE). Participants should be eligible for TACE and able to undergo contrast-enhanced ultrasound (CEUS) imaging. The study aims to include those who can provide informed consent and have no conditions that would interfere with CEUS.

Inclusion Criteria

Have signed informed consent to participate in the study

Be medically stable

I am scheduled for a specific liver tumor treatment.

Exclusion Criteria

Patients with known sensitivities to the components of lumason

Patients who are medically unstable, seriously or terminally ill, or have an unpredictable clinical course

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Imaging

Participants receive Lumason IV and undergo CEUS 2 weeks prior to TACE

2 weeks

1 visit (in-person)

Treatment

Participants undergo CEUS during TACE procedure

During TACE procedure

1 visit (in-person)

Post-Treatment Imaging

Participants undergo CEUS 1-2 weeks after TACE

1-2 weeks

1 visit (in-person)

Follow-up Imaging

Participants undergo CEUS 1-2 months after TACE

1-2 months

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Sulfur Hexafluoride Lipid Microspheres
• Transarterial Chemoembolization

Trial Overview The trial is testing the use of contrast-enhanced ultrasound (CEUS) during TACE procedures in liver tumor patients. It compares CEUS's ability to assess treatment response earlier against standard methods like MRI or CT scans, which are done later.

How Is the Trial Designed?

Group I: Diagnostic (CEUS) Experimental Treatment 4 Interventions

Patients receive lumason IV and undergo CEUS 2 weeks prior to TACE, during TACE, 1-2 weeks after TACE, and then 1-2 months after TACE. Intervention(s)

Transarterial Chemoembolization is already approved in United States, China, European Union for the following indications:

Approved in United States as TACE for:

• Non-small cell lung cancer
• Lung metastases

Approved in China as TACE for:

• Unresectable lung cancer
• Advanced lung cancer

Approved in European Union as TACE for:

• Non-small cell lung cancer
• Lung metastases

Who Is Running the Clinical Trial?

john eisenbrey

Lead Sponsor

Trials

2

Recruited

480+

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 89 hepatocellular carcinoma (HCC) cases, contrast-enhanced ultrasound (CEUS) was found to be as accurate as contrast-enhanced computed tomography (CECT) for evaluating treatment response to transcatheter arterial chemoembolization (TACE) just 1 to 2 days after the procedure.

CEUS demonstrated noninferiority to CECT, with both methods showing an accuracy rate of 83.1%, allowing for early assessment of treatment effectiveness and timely planning for subsequent treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of Contrast-Enhanced Ultrasound for Early Therapeutic Evaluation of Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization. Watanabe, Y., Ogawa, M., Kumagawa, M., et al.[2020]

In a study of 20 patients with hepatocellular carcinoma (HCC), both contrast-enhanced ultrasound (CEUS) and volume perfusion computed tomography (VPCT) effectively assessed early responses to transarterial chemoembolization (TACE), showing comparable results in all cases.

A significant reduction in hepatic perfusion parameters (like HPI, ALP, BV, and BF) was observed in responders one day after TACE, indicating that these measurements can help predict treatment success, with specific cutoff values identified for assessing response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of volume perfusion computed tomography and contrast-enhanced ultrasound for assessment of therapeutic effect of transarterial chemoembolization in patients with hepatocellular carcinoma: a preliminary report. Kaufmann, S., Schulze, M., Spira, D., et al.[2016]

In a study of 330 TACE procedures performed on 170 patients, the overall complication rate was 9.1%, with a significant prevalence of complications in diabetic patients (13.3%) and those with biliary stents (25%).

The findings suggest that diabetes and biliary stents are risk factors for complications after TACE, while the use of new drug-eluting microspheres did not increase complication risk, indicating their safety in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver. Poggi, G., Pozzi, E., Riccardi, A., et al.[2010]

In a study of 12 patients undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), contrast-enhanced ultrasonography (CEUS) was found to detect residual viable HCC earlier than multidetector computed tomography (MDCT), with all patients showing positive CEUS results also confirming HCC viability on MRI.

CEUS demonstrated near-perfect agreement with MRI results (κ=1.00), while MDCT showed only substantial agreement (κ=0.67), indicating that CEUS could serve as a valuable early diagnostic tool for assessing treatment response and guiding further interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study. Cho, YZ., Park, SY., Choi, EH., et al.[2018]

Transarterial chemoembolization (TACE) is a generally safe treatment for unresectable hepatocellular carcinoma (HCC), but it can lead to serious complications, including the rare occurrence of a hepatic artery pseudoaneurysm, as seen in a case involving a 55-year-old male patient.

In this case, the pseudoaneurysm was successfully treated with coil embolization, suggesting that while TACE can have complications, they can often be managed effectively when they arise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Unusual Complication of Transarterial Chemoembolization of Hepatocellular Carcinoma; Pseudoaneurysm: A Case Report. Atay, M., Ozdemir, H.[2022]

Transarterial chemoembolization (TACE) is a generally safe and effective treatment for liver tumors, with a low incidence of major complications, including acute cholecystitis and acute pancreatitis, observed in a study of 196 patients over four years.

The study identified concomitant cardiovascular disease as a significant risk factor for complications following TACE, highlighting the importance of patient assessment before the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of transarterial chemoembolization (TACE) in the treatment of liver tumors. Marcacuzco Quinto, A., Nutu, OA., San Román Manso, R., et al.[2021]

In a study of 73 patients with hepatocellular carcinoma (HCC), those who underwent transarterial chemoembolization (TACE) showed a significantly prolonged washout time of residual tumors on contrast-enhanced ultrasonography (CEUS) compared to untreated HCC nodules, indicating a potential difference in tumor behavior post-treatment.

The study identified various enhancement patterns in the arterial phase of post-TACE residual tumors, suggesting that analyzing washout time and enhancement characteristics can provide valuable insights for guiding further treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced Ultrasound in Residual Tumor of Hepatocellular Carcinoma following Transarterial Chemoembolization: Is It Helpful for Tumor Response? Jiang, T., Zhao, Q., Huang, M., et al.[2022]

In a study of 160 patients with advanced hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) guided by contrast-enhanced ultrasound (CEUS) resulted in fewer repeat procedures and lower serum levels of vascular endothelial growth factor (VEGF), indicating better control of tumor angiogenesis compared to traditional DSA-guided TACE.

Patients receiving CEUS-guided TACE had a higher disease control rate and better overall prognosis, suggesting that this method is effective in managing tumor progression in HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of endostar combined with transcatheter arterial chemoembolization and analysis of vascular endothelial factor and C-reactive protein levels in patients with advanced hepatocellular carcinoma under contrast enhanced ultrasound. Wang, Y., Xuan, Z., Zheng, X., et al.[2020]

In a study of 160 patients with advanced hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) guided by contrast-enhanced ultrasound (CEUS) resulted in fewer repeat procedures and lower serum levels of vascular endothelial growth factor (VEGF), indicating better control of tumor angiogenesis compared to traditional DSA-guided TACE.

Patients receiving CEUS-guided TACE had a higher disease control rate and better overall prognosis, suggesting that this method is effective in managing tumor progression in HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of endostar combined with transcatheter arterial chemoembolization and analysis of vascular endothelial factor and C-reactive protein levels in patients with advanced hepatocellular carcinoma under contrast enhanced ultrasound. Wang, Y., Xuan, Z., Zheng, X., et al.[2020]

In a study of 59 patients with intermediate stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE), the vascularization pattern of the largest tumor lesion was found to significantly impact overall survival, with patients having homogeneously vascularized lesions surviving a median of 1091 days compared to 508 days for those with heterogeneous vascularization.

The findings suggest that assessing the vascularization patterns before TACE could serve as a valuable prognostic tool, potentially aiding in treatment planning and patient stratification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of CT vascularization patterns for survival prognosis in patients with hepatocellular carcinoma treated by conventional TACE. Hasdemir, DB., Dávila, LA., Schweitzer, N., et al.[2018]

In a study of 876 patients with hepatocellular cancer (HCC) undergoing liver transplantation, transarterial chemoembolization (TACE) did not increase the risk of postoperative hepatic artery complications compared to those who did not receive TACE.

The analysis of intraoperative interventions also showed no significant difference in the need for hepatic artery interventions between patients who underwent TACE and those who did not, indicating that TACE is a safe option before liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transarterial chemoembolization of hepatocellular carcinoma before liver transplantation and risk of post-transplant vascular complications: a multicentre observational cohort and propensity score-matched analysis. Sneiders, D., Boteon, APCS., Lerut, J., et al.[2021]

Transarterial chemoembolization (TACE) is a common treatment for hepatocellular carcinoma (HCC), but it can lead to rare complications, including acute pancreatitis.

This case highlights the importance of recognizing acute pancreatitis as a potential adverse effect of TACE, emphasizing the need for careful monitoring during and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute pancreatitis as a complication of trans-arterial chemoembolization of hepatocellular cancer-case report and review of literature. Krishnamurthy, P., Brown, M., Agrawal, S., et al.[2020]

Contrast-enhanced ultrasound (CEUS) demonstrated significantly higher sensitivity (95.9%) and accuracy (96.2%) in detecting residual tumors after transcatheter arterial chemoembolization (TACE) compared to contrast-enhanced computed tomography (CECT), which had sensitivities of 76.2% and accuracy of 77.7%.

CEUS identified fewer complete responses in target and nontarget lesions compared to CECT, suggesting that while CEUS is superior for detecting residual tumors, CECT may still be more effective in assessing overall treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography in evaluating the treatment response to transcatheter arterial chemoembolization of hepatocellular carcinoma using modified RECIST. Liu, M., Lin, MX., Lu, MD., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03407001

Contrast Enhanced Ultrasound With Lumason in Detecting ... PRIMARY OBJECTIVES: I. Determine the accuracy of contrast enhanced ultrasound (CEUS) utilizing contrast agent sulfur hexafluoride lipid-type A microspheres ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5886815/

CONTRAST-ENHANCED ULTRASOUND OF THE LIVER Currently, there are two purely intravascular ultrasound contrast agents with proven track record in liver imaging available for clinical use in the USA.

3. medsci.org medsci.org/v22p1092.htm

Research Progress on Contrast-Enhanced Ultrasound ... This review summarizes the current applications and recent advancements in CEUS-assisted diagnosis and treatment of liver-related diseases

4. prevention.cancer.gov prevention.cancer.gov/clinical-trials/clinical-trials-search/nct03407001

Contrast Enhanced Ultrasound With Lumason in Detecting ... This early phase I trial studies how well contrast enhanced ultrasound with sulfur hexafluoride lipid microspheres (Lumason) works in detecting liver cancer ...

5. withpower.com withpower.com/trial/phase-2-liver-neoplasms-1-2024-537ee

Contrast-Enhanced Ultrasound for Liver Cancer This phase II trial evaluates the diagnostic performance of contrast-enhanced ultrasound (CEUS) for assessing treatment response in patients undergoing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03407001

Contrast Enhanced Ultrasound With Lumason in Detecting ... This early phase I trial studies how well contrast enhanced ultrasound with sulfur hexafluoride lipid microspheres (Lumason) works in detecting liver cancer in ...

7. 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.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2014/203684Orig1s000MedR.pdf

203684Orig1s000 - accessdata.fda.gov In all studies, the ability to delineate the cardiac borders was improved with sulfur hexafluoride lipid microspheres. A 2 ml dose was.

9. asecho.org asecho.org/wp-content/uploads/2019/07/2018-LUMASON-Formulary-Kit-APPROVED.pdf

LUMASON FORMULARY KIT Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following the injection of ultrasound contrast agents, including ...