Contrast-Enhanced Ultrasound for the Prediction of Bile Duct Cancer Response to Radioembolization Treatment

Study Overview
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Brief Summary
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This clinical 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.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the ability of quantitative volumetric contrast-enhanced ultrasound (CEUS) to predict intrahepatic cholangiocarcinoma (ICC) response to transarterial radioembolization (TARE) prior to therapy. SECONDARY OBJECTIVES: I. To characterize the safety and preliminary efficacy of using localized ultrasound contrast agent (UCA) inertial cavitation to improve ICC response to radioembolization. II. To determine if CEUS estimated tumor perfusion and residual vascularity 7-14 days post treatment can predict ICC response to radioembolization. III. To evaluate tumoral response using the patient's 1 month magnetic resonance imaging (MRI) (obtained clinically) and determine the accuracy of MR or computed tomography (CT) tumor evaluation at this earlier time point. EXPLORATORY OBJECTIVE: I. To examine the utility of subharmonic aided pressure estimation (SHAPE) to noninvasively monitor tumoral interstitial fluid pressure (IFP) and provide an early biomarker of radiotherapy response. OUTLINE: Patients receive perflutren protein-type A microspheres intravenously (IV) over 10 minutes and undergo ultrasound at 1 month before TARE, 1-4 hours, 1 week, and 2 weeks post-TARE. After completion of study, patients are followed for 1 year.

Official Title
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Contrast-Enhanced Ultrasound for Diagnosis and Therapy of Cholangiocarcinoma

Conditions
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Intrahepatic Cholangiocarcinoma

Intervention / Treatment
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* Drug: Perflutren Protein-Type A Microspheres
* Procedure: Contrast-Enhanced Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be scheduled for sub-lobar radioembolization therapy of a previously untreated intrahepatic cholangiocarcinoma greater than 1 cm but small enough to be fully visualized in the ultrasound three-dimensional (3D) volume (approximately 6 cm maximum diameter, but depth dependent) Be at least 18 years of age Be medically stable If a female of child-bearing age, have a negative pregnancy test prior to each ultrasound exam Have signed Informed Consent to participate in the study Exclusion Criteria: Females who are pregnant or nursing Patients with recent cerebral hemorrhage Patients with known sensitivities to albumin, blood, or blood products Patients with known hypersensitivity to perflutren Patients with known congenital heart defects Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli Patients with bilirubin levels > 2 mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (perflutren protein-type A microspheres, CEUS)<br>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. | Drug: Perflutren Protein-Type A Microspheres<br>* Given IV<br>* Other names: Optison;Procedure: Contrast-Enhanced Ultrasound<br>* Undergo CEUS<br>* Other names: CEUS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor complete response (CR) and partial response (PR) | Testing for the effect of radioembolization on tumor response will be conducted using non-parametric Mann-Whitney U-tests of the differences in Response Evaluation Criteria in Solid Tumors (mRECIST) distributions between historical controls and enrolled patients. | Up to 6 months post-transarterial radioembolization (TARE) |