Contrast-Enhanced Ultrasound + Radioembolization for Liver Cancer

Overseen By John Eisenbrey, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Disqualifiers: Pregnancy, Medically unstable, Cardiac issues, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to enhance liver cancer therapy. Researchers aim to determine if a special ultrasound with microbubbles can improve the effectiveness of the main treatment, Yttrium-90 Microsphere Radioembolization, a type of internal radiation. Individuals with a liver cancer tumor smaller than 6 cm, visible on a regular ultrasound, and scheduled for a specific type of radiation treatment may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in liver cancer therapy.

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's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that perflutren protein-type A microspheres, used in contrast-enhanced ultrasound, are generally well-tolerated. These tiny gas bubbles enhance ultrasound images and have been safely used in studies, typically measuring 2.5 to 4.5 micrometers. Some side effects, such as headaches or dizziness, have been reported but are usually mild. Serious reactions are rare. Contrast-enhanced ultrasound is a safe and reliable imaging method, especially for liver conditions.

Research indicates that yttrium-90 microsphere radioembolization is a targeted treatment for liver cancer. This method has been widely used and is considered safe, though some patients may experience mild fatigue or discomfort afterward.

In summary, both parts of the trial treatment have demonstrated safety in other studies. Participants might experience mild side effects, but serious issues are uncommon. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for liver cancer, like surgery and chemotherapy, aim to remove or kill cancer cells directly. However, researchers are excited about the use of contrast-enhanced ultrasound (CEUS) combined with yttrium-90 radioembolization because it offers a more precise way to target tumors. This approach uses tiny radioactive beads to deliver radiation directly to the cancer site, minimizing damage to surrounding healthy tissue. The addition of CEUS helps doctors visualize and monitor the effectiveness of the treatment in real-time, potentially improving outcomes and allowing for more personalized treatment plans.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that tiny bubbles called perflutren protein-type A microspheres, used with a special ultrasound technique, can make tumors more responsive to radiation treatments like radioembolization. In this trial, one group of participants will receive perflutren protein-type A microspheres and undergo contrast-enhanced ultrasound (CEUS) to potentially enhance liver cancer treatment effectiveness. Studies indicate that this ultrasound method helps doctors see liver tumors more clearly, improving targeting accuracy. Early findings suggest that combining these microbubbles with ultrasound might enhance radiation treatments by making tumors easier to locate and treat. ^{1 3 6 7 8}

Who Is on the Research Team?

John Eisenbrey, PhD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for stable adults with untreated liver cancer (HCC) masses under 6 cm, visible on ultrasound. They must consent to the study and women of childbearing age need a negative pregnancy test before each exam. It's not for critically ill patients, those with high bilirubin levels or heart failure, pregnant/nursing women, or anyone allergic to perflutren.

Inclusion Criteria

Have signed informed consent to participate in the study

I am scheduled for a specific liver cancer treatment for a tumor smaller than 6 cm.

Be medically stable

Exclusion Criteria

I have a known heart shunt.

I have severe emphysema, pulmonary vasculitis, or a history of pulmonary embolism.

I have a history of bleeding disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive perflutren protein-type A microspheres intravenously and undergo contrast-enhanced ultrasound, or undergo standard of care yttrium Y-90 radioembolization

2 weeks

Multiple visits for CEUS at 1-6 hours, 7 days, and 14 days post-radioembolization

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 months

Follow-up visits at 1 month and 3-4 months

What Are the Treatments Tested in This Trial?

Interventions

• Dynamic Contrast-Enhanced Ultrasound Imaging
• Perflutren Protein-Type A Microspheres
• Yttrium-90 Microsphere Radioembolization

Trial Overview

The trial tests if using Perflutren Protein-Type A Microspheres with contrast-enhanced ultrasound can improve the effectiveness of Yttrium-90 radioembolization therapy in treating liver cancer by making tumors more sensitive to radiation.

How Is the Trial Designed?

Group I: Group I (perflutren protein-type A microspheres, CEUS) Experimental Treatment 3 Interventions

Patients receive perflutren protein-type A microspheres IV over 10 minutes and undergo CEUS over 60 minutes at 1-6 hours and at approximately 7 and 14 days after yttrium Y-90 radioembolization.

Group II: Group II (standard of care) Active Control 1 Intervention

Patients undergo standard of care yttrium Y-90 radioembolization.

Yttrium-90 Microsphere Radioembolization is already approved in United States, European Union for the following indications:

Approved in United States as Yttrium-90 Microspheres for:

• Hepatocellular carcinoma
• Colorectal cancer liver metastases

Approved in European Union as Yttrium-90 Microspheres for:

• Hepatocellular carcinoma
• Colorectal cancer liver metastases

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Sidney Kimmel Cancer Center at Thomas Jefferson University

Lead Sponsor

Trials

164

Recruited

10,900+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Selective intraarterial radionuclide therapy (SIRT) using Yttrium-90 microspheres is a safe and effective treatment for unresectable hepatic metastases from neuroendocrine tumors, with a high overall response rate of 90% in a study of 10 patients.

The treatment delivered a significant dose of radiation directly to the tumors (mean 99.73 Gy) while minimizing exposure to healthy liver tissue (mean 26.73 Gy) and lungs (mean 4.45 Gy), indicating its targeted approach reduces potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for hepatic neuroendocrine metastases: initial experience at a single center. Arslan, N., Emi, M., Alagöz, E., et al.[2019]

Selective internal radiotherapy (SIRT) using yttrium-90 microspheres can enhance clinical outcomes for patients with inoperable liver cancer by targeting tumors while protecting healthy tissue.

Effective planning for SIRT is crucial to avoid serious side effects like radiation-induced liver disease, and it is recommended to use multiple planning methods to determine the appropriate microsphere activity for each patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Lau, WY., Kennedy, AS., Kim, YH., et al.[2022]

In a study involving 28 patients with unresectable hepatocellular carcinoma (HCC), Y-90 microsphere therapy demonstrated safety and efficacy, with no significant complications observed during or shortly after treatment.

The therapy resulted in a complete response in 7% of patients and a partial response in 36%, indicating that it can effectively target liver tumors while minimizing damage to healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 (Y-90) Resin Microsphere Therapy for Patients with Unresectable Hepatocellular Carcinoma: a Single-Center Experience. İnce, S., Karaman, B., Alagoz, E., et al.[2019]

In a study of 111 patients with unresectable hepatocellular carcinoma (HCC) treated with Y-90 resin microspheres, factors such as early-stage disease and absence of complications like portal vein thrombosis were linked to significantly longer overall survival, with patients in the early-stage group living an average of 27.8 months compared to just 9.2 months for those in advanced stages.

Y-90 resin treatment was generally well-tolerated, with adverse events reported in 23 patients shortly after treatment and 46 patients at 3 months, indicating that while some side effects occurred, the therapy was manageable and could be an effective option for bridging patients to liver transplantation, which further improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study. Mantry, PS., Mehta, A., Madani, B., et al.[2022]

In a study involving 34 patients with unresectable hepatocellular carcinoma (HCC), Yttrium-90 (Y-90) microsphere therapy demonstrated significant efficacy, with 19% achieving complete response and 44% showing partial response after treatment.

The therapy was found to be safe, with no serious side effects reported, and predictors of treatment success included mean tumor dose delivery and the absence of bilobar disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 (Y-90) resin microsphere therapy for patients with unresectable hepatocellular carcinoma. Identification of successful treatment response predictors and patient selection. Arslan, N., Ince, S., Okuyucu, K., et al.[2022]

In a study of 60 patients with liver metastases from colorectal cancer, higher prescribed activity of Yttrium-90 resin microspheres was associated with improved radiographic tumor response at 4-6 months post-treatment, as measured by RECIST criteria.

Overall survival was not significantly linked to the prescribed activity or dose, suggesting that while the treatment may improve tumor response, it does not necessarily extend survival, highlighting the need for better dose calculation models for predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of radiation dose and activity with clinical outcomes in metastatic colorectal cancer after selective internal radiation therapy using yttrium-90 resin microspheres. Badiyan, S., Bhooshan, N., Chuong, MD., et al.[2019]

Citations

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The aim of the present study was to investigate the imaging features observed in pre-operative Sonazoid contrast-enhanced ultrasound (SZ-CEUS)