Contrast-Enhanced Ultrasound Identification of Sentinel Nodes in Esophageal Cancer

This pilot trial studies how well an ultrasound with a contrast agent (perflubutane microbubble [Sonazoid]) works in identifying sentinel lymph nodes in participants with esophageal cancer. Sentinel lymph nodes are lymph nodes to which the cancer is likely to spread from the primary tumor. Diagnostic procedures, such as contrast-enhanced ultrasound, may work better in identifying sentinel lymph nodes and finding out how far the disease has spread.

Study Overview

• Status: Completed
• Conditions: Esophagus
• Intervention / Treatment: Procedure: Contrast-Enhanced Ultrasound; Procedure: Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA); Procedure: Fine-Needle Aspiration; Drug: Sonazoid (Perflubutane)

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the accuracy of contrast-enhanced endoscopic lymphosonography guided fine-needle aspiration (FNA) of sentinel lymph nodes compared with unenhanced endoscopic ultrasonography (EUS) guided FNA in the characterization of esophageal cancer-associated lymph nodes using pathology as the reference standard.

SECONDARY OBJECTIVES:

I. To assess the ability of contrast-enhanced endoscopic lymphosonography guided FNA compared with unenhanced EUS guided FNA in the overall detection of biopsy proven cancer-involved sentinel lymph nodes.

II. To assess the impact of overall tumor staging by contrast-enhanced endoscopic lymphosonography compared with unenhanced EUS.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Early Phase 1

Contacts and Locations

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: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed with esophageal cancer.
• Be scheduled for staging endoscopic ultrasound with the intent for lymph node evaluation.
• Provide signed and dated informed consent form.
• Willing to comply with all study procedures and be available for the duration of the study.
• Be medically stable.
• If a female and pre-menopausal, must have a negative pregnancy test.

Exclusion Criteria:

• Females who are pregnant or nursing.
• Patients with other primary cancers requiring systemic treatment.
• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable.
• Patients with known hypersensitivity or allergy to any component of Sonazoid.
• Patients with cardiac shunts or unstable cardiopulmonary conditions.
• Patients with congenital heart defects.
• Patients with severe emphysema, pulmonary vasculitis, pulmonary hypertension, respiratory distress syndrome, or a history of pulmonary embolism.

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 (EUS, FNA, perflubutane microbubble); Participants undergo standard of care unenhanced endoscopic ultrasound (EUS) and fine needle aspiration (FNA) of identified lymph nodes. Participants then receive perflubutane microbubble peri- or intratumorally and undergo contrast-enhanced EUS followed by FNA of identified lymph nodes.

Procedure: Contrast-Enhanced Ultrasound; Undergo CEUS; Procedure: Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA); Undergo EUS-FNA; Procedure: Fine-Needle Aspiration; Undergo FNA; Drug: Sonazoid (Perflubutane); Sonazoid (ultrasound contrast agent) will be injected in 0.25 mL increments at 12, 3, 6, and 9 o'clock positions around the tumor using a 19 - 22 gauge needle system under EUS guidance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy rate of traditional endoscopic ultrasonography (EUS) with suspicious node biopsy and lymphosonography for sentinel node identification	The number and locations of the nodes identified by the two imaging approaches (contrast-enhanced ultrasound [CEUS] and unenhanced EUS) will be compared using McNemar's test for correlated proportions as well as using a one-sided t-test with a Wilcoxon non-parametric adjustment (normal distribution will be tested) with pathology as the reference standard for sentinel lymph node detection and considering exact binomial p-values less than 0.05 to be significant. The findings of lymphosonography will be correlated to pathological findings (including degree of metastatic involvement) to determine sensitivity and specificity and the rate of cancerous nodes identified by CEUS relative to those of unenhanced EUS using a clustered conditional logistic regression analysis of correlated proportions (equivalent to a clustered McNemar's test).	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of nodes identified	The number and locations of the nodes identified by the two imaging approaches (CEUS and unenhanced EUS) will be compared using McNemar's test for correlated proportions as well as using a one-sided t-test with a Wilcoxon non-parametric adjustment (normal distribution will be tested) with pathology as the reference standard for sentinel lymph node detection and considering exact binomial p-values less than 0.05 to be significant. The findings of lymphosonography will be correlated to pathological findings (including degree of metastatic involvement) to determine sensitivity and specificity and the rate of cancerous nodes identified by CEUS relative to those of unenhanced EUS using a clustered conditional logistic regression analysis of correlated proportions (equivalent to a clustered McNemar's test).	Up to 2 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ji-Bin Liu, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2018
• Primary Completion (Actual): August 25, 2022
• Study Completion (Actual): August 25, 2022

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (Actual): July 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: 18F.235; R21CA218946 (U.S. NIH Grant/Contract); JT 12449 (Other Identifier: JeffTrial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No