Contrast-Enhanced Ultrasound for Bile Duct Cancer

Overseen By John Eisenbrey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Disqualifiers: Pregnancy, Cerebral hemorrhage, Hypersensitivity, 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: 2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether contrast-enhanced ultrasound can predict the response of bile duct cancer to targeted radiotherapy (radioembolization treatment). Contrast-enhanced ultrasound uses gas microbubbles that may provide enhancement on ultrasound. It is also possible to pop these microbubbles using ultrasound imaging. Tumors that experience popping of these microbubbles may be easier to kill with radiotherapies. Therefore, this trial may also help doctors see if ultrasound-triggered microbubble popping can improve bile duct cancer response to radiotherapy. Another purpose of this trial is to test if the pressure inside the tumor estimated through ultrasound can be used to predict the tumor response to radiotherapy.

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.

What data supports the effectiveness of the treatment Perflutren Protein-Type A Microspheres, Optison, Perflutren Protein-Type A Microspheres, Radioembolization Treatment, Selective Internal Radiotherapy (SIRT), Y-90 Treatment, Radioembolization using Yttrium-90 (90Y)–labeled microspheres for bile duct cancer?

Research shows that Selective Internal Radiotherapy (SIRT) with Yttrium-90 (Y-90) microspheres has been effective in treating various liver cancers, including intrahepatic cholangiocarcinoma (a type of bile duct cancer), by delivering targeted radiation to tumors while sparing healthy liver tissue. ^{1 2 3 4 5}

Is Yttrium-90 treatment generally safe for humans?

Yttrium-90 (Y-90) treatment, also known as Selective Internal Radiation Therapy (SIRT) or radioembolization, has been used safely in treating various liver cancers. While it delivers high doses of radiation to tumors, it minimizes exposure to healthy liver tissue, though there can be complications like unintended radiation to nearby areas such as the gallbladder. ^{1 3 4 5 6}

How is the Radioembolization Treatment for bile duct cancer different from other treatments?

Radioembolization Treatment, also known as Selective Internal Radiotherapy (SIRT), is unique because it delivers high doses of radiation directly to the tumor in the liver using tiny radioactive beads (Yttrium-90 microspheres), minimizing exposure to healthy liver tissue. This targeted approach is different from traditional treatments that may affect more of the surrounding healthy tissue. ^{1 2 3 5 7}

Eligibility Criteria

This trial is for adults with untreated intrahepatic cholangiocarcinoma (bile duct cancer) that's larger than 1 cm but small enough to be seen in a 3D ultrasound. Participants must be medically stable and not pregnant if female of child-bearing age. Exclusions include recent cerebral hemorrhage, pregnancy, high bilirubin levels, allergy to perflutren or albumin, congenital heart defects, severe lung conditions.

Inclusion Criteria

I am of childbearing age and have a negative pregnancy test before each ultrasound.

I am 18 years old or older.

Have signed Informed Consent to participate in the study

Exclusion Criteria

I have had a recent brain bleed.

I was born with a heart defect.

Patients with known hypersensitivity to perflutren

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Assessment

Patients receive perflutren protein-type A microspheres IV and undergo ultrasound 1 month before TARE

1 month

1 visit (in-person)

Treatment

Patients undergo transarterial radioembolization (TARE) and receive ultrasound assessments at 1-4 hours, 1 week, and 2 weeks post-TARE

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments up to 6 months post-TARE

6 months

Multiple visits (in-person)

Treatment Details

Interventions

• Perflutren Protein-Type A Microspheres
• Radioembolization Treatment

Trial Overview The study tests if contrast-enhanced ultrasound can predict how well bile duct cancer responds to radioembolization treatment. It involves using gas microbubbles in the ultrasound which may pop and potentially make tumors more susceptible to radiotherapy. The trial also examines whether tumor pressure measured by ultrasound predicts treatment response.

Participant Groups

Group I: Diagnostic (perflutren protein-type A microspheres, CEUS) Experimental Treatment 2 Interventions

Patients receive perflutren protein-type A microspheres IV over 10 minutes and undergo ultrasound at 1 month before TARE, 1-4 hours, 1 week, and 2 weeks post-TARE.

Radioembolization Treatment is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Radioembolization for:

• Unresectable intrahepatic cholangiocarcinoma
• Locally advanced intrahepatic cholangiocarcinoma

Approved in United States as Radioembolization for:

• Unresectable intrahepatic cholangiocarcinoma
• Locally advanced intrahepatic cholangiocarcinoma
• Metastatic liver disease

Approved in Canada as Radioembolization for:

• Unresectable intrahepatic cholangiocarcinoma
• Locally advanced intrahepatic cholangiocarcinoma

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Findings from Research

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]

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]

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]

In a study of 17 patients with unresectable and metastatic intrahepatic cholangiocarcinoma (ICC) treated with Yttrium-90 (Y-90), the five-year overall survival rate was 26.8%, with a median survival of 33.6 months, indicating promising efficacy.

The treatment was found to be safe, with no 90-day mortality reported and only two complications noted, suggesting that Y-90 could be a viable option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma? Shaker, TM., Chung, C., Varma, MK., et al.[2019]

Selective internal radiotherapy (SIRT) using yttrium-90 (Y90) is effective for treating unresectable liver tumors, but it can unintentionally irradiate the gallbladder, leading to complications.

In a study of 295 patients, strategies like occluding the cystic artery or altering catheter positions significantly reduced the risk of gallbladder irradiation, with only one case of cholecystitis observed, which was successfully treated without the need for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiotherapy (SIRT) of hepatic tumors: how to deal with the cystic artery. Theysohn, JM., Müller, S., Schlaak, JF., et al.[2016]

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]

References

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

Yttrium-90 (Y-90) Resin Microsphere Therapy for Patients with Unresectable Hepatocellular Carcinoma: a Single-Center Experience. [2019]

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

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. [2022]

3. Serbia 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. [2019]

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

Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma? [2019]

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

Selective internal radiotherapy (SIRT) of hepatic tumors: how to deal with the cystic artery. [2016]

6. China pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study. [2022]

7. Italy 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. [2022]