Contrast Enhanced Ultrasound to Evaluate Response to Chemoembolization in Patients With Liver Tumors

2D and 3D Contrast Enhanced Ultrasound of Chemoembolization

This phase II trial evaluates the diagnostic performance of contrast-enhanced ultrasound (CEUS) for assessing treatment response in patients undergoing transarterial chemoembolization (TACE) for liver tumors. TACE is a hepatic artery embolization technique involving the injection of a blocking agent and a chemotherapy agent to treat liver cancers. Currently, contrast enhanced magnetic resonance imaging or computed tomography are used to assess disease response 1-2 months after TACE treatment, but ultrasound may be a less expensive, earlier alternative. CEUS is an imaging procedure that uses high-frequency sound waves to generate images of the body after administering lumason, an imaging agent used to enhance visualization of blood flow on ultrasounds. CEUS is able to be performed during the TACE procedure, making it possible to evaluate treatment response earlier than standard techniques. CEUS may be an effective method to evaluate treatment response more accurately and much earlier than current standard evaluation methods.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Neoplasms
• Intervention / Treatment: Procedure: Contrast-Enhanced Ultrasound; Drug: Sulfur Hexafluoride Lipid Microspheres; Other: Medical Chart Review; Procedure: Transarterial Chemoembolization

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the sensitivity and specificty of CEUS for the evaluation of TACE treatment response in a variety of solid liver tumors (years 1-4).

SECONDARY OBJECTIVES:

I. To determine the ability of CEUS to identify residual tumor vascularity intraoperatively, thereby enabling immediate retreatment when necessary (years 1-4).

II. To explore a variety of advanced imaging approaches to improve on the suboptimal specificity of CEUS for identifying residual viable tumor following TACE (years 1-5).

III. To investigate the ability of CEUS obtained prior to TACE to quantitatively assess tumor vascular morphology and predict response to therapy (years 2-5).

EXPLORATORY OBJECTIVE:

I. Use acquired B-mode in-phase and quadrature (IQ) data for H-scan imaging.

OUTLINE:

Patients receive lumason intravenously (IV) and undergo CEUS 2 weeks prior to TACE, during TACE, 1-2 weeks after TACE, and then 1-2 months after TACE.

After completion of study treatment, patients are followed up at 6 months.

• Study Type: Interventional
• Enrollment (Estimated): 266
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: John Eisenbrey, PhD; Phone Number: 215-503-5188; Email: john.eisenbrey@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Scheduled for TACE therapy of a liver tumor
• Be at least 18 years of age
• Be medically stable
• If a female of child-bearing age, must have a negative pregnancy test
• Have signed informed consent to participate in the study

Exclusion Criteria:

• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable
• Patients with known sensitivities to the components of lumason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic (CEUS); Patients receive lumason IV and undergo CEUS 2 weeks prior to TACE, during TACE, 1-2 weeks after TACE, and then 1-2 months after TACE. Intervention(s)	Procedure: Contrast-Enhanced Ultrasound; Undergo CEUS; Other Names: CEUS; Drug: Sulfur Hexafluoride Lipid Microspheres; Given IV; Other Names: Lumason; SF6 Lipid Microspheres; Sulfur Hexafluoride Lipid-type A Microspheres; Other: Medical Chart Review; Ancillary studies; Other Names: Chart Review; Procedure: Transarterial Chemoembolization; Undergo TACE; Other Names: TACE; Chemoembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence	Will be computed using a reference standard. Variables will be summarized with descriptive statistics, such as means with standard deviations or frequency counts with percentage, across the cohort and within group of interest. Diagnostic accuracy will be compared between hepatocellular carcinoma (HCC) and non-HCC and between all tumor subtypes.	Up to 6 months
Specificity	Will be computed using a reference standard. Variables will be summarized with descriptive statistics, such as means with standard deviations or frequency counts with percentage, across the cohort and within group of interest. Diagnostic accuracy will be compared between HCC and non-HCC and between all tumor subtypes.	Up to 6 months
Positive predictive value	Will be computed using a reference standard. Variables will be summarized with descriptive statistics, such as means with standard deviations or frequency counts with percentage, across the cohort and within group of interest. Diagnostic accuracy will be compared between HCC and non-HCC and between all tumor subtypes.	Up to 6 months
Negative predictive value	Will be computed using a reference standard. Variables will be summarized with descriptive statistics, such as means with standard deviations or frequency counts with percentage, across the cohort and within group of interest. Diagnostic accuracy will be compared between HCC and non-HCC and between all tumor subtypes.	Up to 6 months
False discovery rate	Will be computed using a reference standard. Variables will be summarized with descriptive statistics, such as means with standard deviations or frequency counts with percentage, across the cohort and within group of interest. Diagnostic accuracy will be compared between HCC and non-HCC and between all tumor subtypes.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual tumor vacularity	Will use diagnostic summary statistics and generalized estimating equations (GEE) logistic regression modeling. The bedside (interventional radiologist) versus offline (radiologist) reads will be compared using agreement, kappa statistics, and mixed modeling.	Up to 6 months
Diagnostic performance for each imaging mode	The diagnostic performance for each reader will be quantified from the volumetric contrast enhanced ultrasound exams and post-processed images. Diagnostic performance for each imaging mode will be compared across all readers using the GEE logistic regression approach. Quantitative H-scan data will be compared between complete and incomplete responders using multiple linear regression or GEE regression modeling, depending on how well assumptions hold for the former.	Up to 6 months
Ability of the model to predict binary treatment response	Model performance will be calculated using a leave-one-out cross-validation method to assess the ability of the model to predict binary treatment response. Accuracy, sensitivity and specificity will then be quantified and directly compared between 2 dimensional (D) and 3D datasets.	Up to 6 months

Collaborators and Investigators

• Sponsor: john eisenbrey

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: February 7, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: iRISID-2023-2142

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No