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

Phase 2

Completed

Conditions: Intrahepatic Cholangiocarcinoma

Interventions: Drug: Perflutren Protein-Type A Microspheres
Procedure: Contrast-Enhanced Ultrasound

Registration Number: NCT05328167

Lead Sponsor: Thomas Jefferson University

Brief Summary: 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.

Detailed Description: PRIMARY OBJECTIVE:

I. To determine the ability of quantitative volumetric contrast-enhanced ultrasound (CEUS) to predict non-hepatocellular carcinoma (HCC) tumor 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (perflutren protein-type A microspheres, CEUS)	Perflutren Protein-Type A Microspheres	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.
Diagnostic (perflutren protein-type A microspheres, CEUS)	Contrast-Enhanced Ultrasound	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Tumor Complete Response (CR)	assessed at 3 to 6 months post-TARE	Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Number of Participants With Tumor Partial Response (PR)	assessed at 3 to 6 months post-TARE	Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Number of Participants With Stable Disease	assessed at 3 to 6 months post-TARE	Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.
Number of Participants With Progressive Disease	assessed at 3 to 6 months post-TARE	Assessed by modified RECIST (mRECIST) criteria using contrast-enhanced CT or MRI reviewed by two independent readers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), indicated by a significant increase (at least 20%) in target lesions or the appearance of new target lesions; Stable Disease (SD) means neither the criteria for PR nor for Progressive Disease (PD) have been met.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (1): Sidney Kimmel Cancer Center at Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States
Sidney Kimmel Cancer Center at Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
John Eisenbrey, MD
Contact
215-503-5188
john.eisenbrey@jefferson.edu