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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special type of ultrasound, using tiny gas bubbles, can predict how well bile duct cancer responds to a specific radiotherapy called Radioembolization Treatment (also known as Selective Internal Radiotherapy or Y-90 Treatment). When these bubbles pop, they might enhance the cancer's responsiveness to treatment. The trial will also assess whether measuring tumor pressure with ultrasound can provide insights into treatment success. Individuals who have not yet received treatment for bile duct cancer and are scheduled for this specific type of radiotherapy might be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in cancer care.

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 prior data suggests that contrast-enhanced ultrasound is safe for predicting bile duct cancer response to radiotherapy?

Research has shown that perflutren protein-type A microspheres are usually safe, but some risks exist. In previous studies, some individuals experienced serious allergic reactions, including shock and heart or lung problems. Although rare, these events can be serious.

Perflutren microspheres are often used in heart imaging, indicating they are already approved for other uses and have undergone safety testing. However, when considering participation in a clinical trial, it's important to weigh these risks. Those with concerns should consult a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using contrast-enhanced ultrasound (CEUS) for bile duct cancer because it offers a non-invasive way to visualize tumors in real time. Unlike traditional imaging methods, CEUS uses perflutren protein-type A microspheres, which enhance ultrasound images, allowing doctors to monitor treatment effects more closely and adjust as needed. This approach could make it easier to see how well radioembolization treatment, a procedure that delivers radiation directly to tumors, is working, potentially leading to more personalized and effective care for patients.

What evidence suggests that contrast-enhanced ultrasound is effective for predicting bile duct cancer response to radiotherapy?

Research has shown that contrast-enhanced ultrasound might help predict how well bile duct cancer responds to radiotherapy. In this trial, participants will receive perflutren protein-type A microspheres, tiny bubbles that clarify ultrasound images, enabling doctors to see tumors more clearly. Early studies suggest that when these bubbles burst, they might increase tumor sensitivity to treatments like radiotherapy. Researchers are exploring whether this method can enhance the success of radioembolization, a targeted form of radiotherapy. Although still under investigation, this technique could potentially lead to better outcomes for bile duct cancer patients. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Have signed Informed Consent to participate in the study

Be medically stable

Exclusion Criteria

I have had a recent brain bleed.

I was born with a heart defect.

Patients with known hypersensitivity to perflutren

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05328167?term=HUMAN%20ALBUMIN%20MICROSPHERES%20AND%20PERFLUTREN&viewType=Table&rank=2

Contrast-Enhanced Ultrasound for the Prediction of Bile ... This phase II trial tests whether contrast-enhanced ultrasound can predict the response of bile duct cancer to targeted radiotherapy (radioembolization ...

2. withpower.com withpower.com/trial/phase-2-intrahepatic-cholangiocarcinoma-11-2021-d58fe

Contrast-Enhanced Ultrasound for Bile Duct Cancer This phase II trial tests whether contrast-enhanced ultrasound can predict the response of bile duct cancer to targeted radiotherapy (radioembolization ...

3. trialx.com trialx.com/clinical-trials/listings/250372/contrast-enhanced-ultrasound-for-the-prediction-of-bile-duct-cancer-response-to-radioembolization-treatment/?&geo_lat=40.0&geo_lng=-75.276&radius=10&place=Wynnewood&user_country=United%20States

Contrast-Enhanced Ultrasound for the Prediction of Bile Duct ... This phase II trial tests whether contrast-enhanced ultrasound can predict the response of bile duct cancer to targeted radiotherapy (radioembolization ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-01036

Perflutren Protein-Type A Microspheres and Contrast ... This phase II trial studies how well perflutren protein-type A microspheres and contrast-enhanced ultrasound work in improving response to radioembolization ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4676450/

Update on the safety and efficacy of commercial ultrasound ... Optison consists of microspheres of protein-type A microspheres that contain perflutren. ... Clinical usefulness of contrast-enhanced three-dimensional ultrasound ...

6. gehealthcare.com gehealthcare.com/-/media/gehc/us/files/products/contrast-media/optison/optison-important-safety-information-9-2021.pdf?rev=-1&srsltid=AfmBOoqWhgzDtgg9ZbOg5UKt3K36JN1I1_VLcfHrjvMCC9wz6DHJQ7Fq

OPTISON Serious anaphylactic reactions have been observed during or shortly following perflutren-containing microsphere administration, including shock, ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/020899s015lbl.pdf

OPTISON™ (Perflutren Protein-Type A Microspheres ... Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration. Most ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/perflutren-protein-type-a-microsphere-intravenous-route/description/drg-20061498

Perflutren protein type a microsphere (intravenous route) Perflutren protein type A microsphere injection is used during an echocardiogram to help diagnose or find problems in the heart.

9. rxlist.com rxlist.com/optison-drug.htm

Optison (Perflutren Protein-Type A Microspheres) The safety of OPTISON was evaluated in 279 adult patients ... There are no data on the presence of perflutren protein-type A microspheres ...