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

Phase 2
Recruiting
Conditions
Liver Neoplasms
Interventions
Drug: Sulfur Hexafluoride Lipid Microspheres
Procedure: Contrast-Enhanced Ultrasound
Procedure: Transarterial Chemoembolization
Other: Medical Chart Review
Registration Number
NCT06261814
Lead Sponsor
john eisenbrey
Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the sensitivity and specificity 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 sulfur hexafluoride lipid microspheres (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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
266
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Diagnostic (CEUS)Contrast-Enhanced UltrasoundPatients 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)
Diagnostic (CEUS)Sulfur Hexafluoride Lipid MicrospheresPatients 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)
Diagnostic (CEUS)Transarterial ChemoembolizationPatients 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)
Diagnostic (CEUS)Medical Chart ReviewPatients 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)
Primary Outcome Measures
NameTimeMethod
RecurrenceUp to 6 months
SensitivityUp to 6 months

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.

SpecificityUp to 6 months

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.

Positive predictive valueUp to 6 months

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.

Negative predictive valueUp to 6 months

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.

False discovery rateUp to 6 months

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.

Secondary Outcome Measures
NameTimeMethod
Ability of the model to predict binary treatment responseUp to 6 months

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.

Residual tumor vacularityUp to 6 months

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.

Diagnostic performance for each imaging modeUp to 6 months

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.

Trial Locations

Locations (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

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Philadelphia, Pennsylvania, United States

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