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

Trial Summary

What is the purpose of this trial?

This phase II trial evaluates the diagnostic performance of contrast-enhanced ultrasound (CEUS) for assessing treatment response in patients undergoing transarterial chemoembolization (TACE) for liver tumors. TACE is a hepatic artery embolization technique involving the injection of a blocking agent and a chemotherapy agent to treat liver cancers. Currently, contrast enhanced magnetic resonance imaging or computed tomography are used to assess disease response 1-2 months after TACE treatment, but ultrasound may be a less expensive, earlier alternative. CEUS is an imaging procedure that uses high-frequency sound waves to generate images of the body after administering Lumason, an imaging agent used to enhance visualization of blood flow on ultrasounds. CEUS is able to be performed during the TACE procedure, making it possible to evaluate treatment response earlier than standard techniques. CEUS may be an effective method to evaluate treatment response more accurately and much earlier than current standard evaluation methods.

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 data supports the effectiveness of the treatment Sulfur Hexafluoride Lipid Microspheres, Lumason, and Transarterial Chemoembolization (TACE) for liver cancer?

Research shows that using contrast-enhanced ultrasound (CEUS) to guide transarterial chemoembolization (TACE) can help evaluate and improve treatment response in patients with liver cancer. This suggests that CEUS, when combined with TACE, may be effective in treating liver cancer. ^{1 2 3 4 5}

Is contrast-enhanced ultrasound for liver cancer safe?

Transarterial chemoembolization (TACE), a related procedure, is generally considered safe but can have complications like liver abscess, liver failure, and acute cholecystitis (inflammation of the gallbladder). These complications are rare but important to be aware of when considering similar treatments. ^{6 7 8 9 10}

How is the treatment Transarterial Chemoembolization (TACE) for liver cancer different from other treatments?

Transarterial Chemoembolization (TACE) is unique because it delivers chemotherapy directly to the liver tumor through the blood vessels, blocking the tumor's blood supply and trapping the drug inside the tumor. This targeted approach can be more effective and less harmful to the rest of the body compared to traditional chemotherapy, which circulates throughout the entire body. ^{3 5 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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 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]

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 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 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]

References

1. Cyprus 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. [2020]

2. Cyprus 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. [2020]

3. Germany 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. [2020]

4. Turkey pubmed.ncbi.nlm.nih.gov

Evaluation of CT vascularization patterns for survival prognosis in patients with hepatocellular carcinoma treated by conventional TACE. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Utility of Contrast-Enhanced Ultrasound for Early Therapeutic Evaluation of Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization. [2020]

6. Greece pubmed.ncbi.nlm.nih.gov

Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver. [2010]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

An Unusual Complication of Transarterial Chemoembolization of Hepatocellular Carcinoma; Pseudoaneurysm: A Case Report. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

Complications of transarterial chemoembolization (TACE) in the treatment of liver tumors. [2021]

9. England 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. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Acute pancreatitis as a complication of trans-arterial chemoembolization of hepatocellular cancer-case report and review of literature. [2020]

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

Contrast-Enhanced Ultrasound in Residual Tumor of Hepatocellular Carcinoma following Transarterial Chemoembolization: Is It Helpful for Tumor Response? [2022]

12. England 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. [2016]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study. [2018]