Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions (EAGLE)

Molecular Fluorescence Endoscopy for the Detection of (Pre)Malignant Lesions in Barrett's Esophagus Using a Fluorescent Tracer 'EMI-137' Targeting c-Met: a Single-center Feasibility and Safety Study

To improve detection of esophageal (pre)malignant lesions during surveillance endoscopy of patients at risk of developing malignancies, for example in Barrett's Esophagus (BE), there is a need for better endoscopic visualization and the ability for targeted biopsies. Optical molecular imaging of neoplasia associated biomarkers could form a promising technique to accommodate this need. It is known that the biomarker c-Met is overexpressed in dysplastic and neoplastic areas in BE segments versus normal tissue and has proven to be a valid target for molecular imaging.

Edinburgh Molecular Imaging Ltd (EMI) has developed a fluorescent tracer specifically targeting c-Met by labeling a small peptide to a fluorescent fluorophore: 'EMI-137'. The investigators hypothesize that when EMI-137 is administered intravenously, it accumulates in c-Met expressing high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), enabling (early) cancer visualization using a newly developed fluorescent fiber-bundle. This hypothesis will be tested in the current pilot intervention study.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer; Barrett Esophagus; Dysplasia in Barrett Esophagus
• Intervention / Treatment: Drug: IV-administation of EMI-137; Device: Molecular Fluorescence Endoscopy platform

Detailed Description

See brief summary.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years, eligible for a diagnostic and/or therapeutic endoscopy;
• At least a suspicion of low grade dysplasia (LGD) based on a prior endoscopy;
• World Health Organization (WHO) performance score of 0-2;
• Written informed consent;
• Mentally competent person that is able and willing to comply with study procedures;

• For female subjects who are of childbearing potential, are premenopausal with intact reproductive organs or are less than 2 years post-menopausal:

  • A negative serum pregnancy test prior to receiving the tracer;
  • Willing to ensure that she or her partner uses effective contraception during the trial and for 3 months thereafter.

Exclusion Criteria:

• Pregnancy or breast feeding;
• Advanced stage EAC patient not suitable for endoscopic resection;
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent;
• Concurrent anticancer therapy (chemotherapy, radiotherapy, vaccines, immunotherapy) delivered within the last three months prior to the start of the treatment
• The subject has been included previously in this study or has been injected with another investigational medicinal product within the past six months.
• History of myocardial infarction (MI), Transient Ischemic Attack (TIA), CerebroVascular Accident (CVA), pulmonary embolism, uncontrolled congestive heart failure (CHF), significant liver disease, unstable angina within 6 months prior to enrollment.
• The subject had any significant change in their regular prescription or non-prescription medication between 14 days and 1 day prior to Investigational Medicinal Product (IMP) administration. Occasional use of analgesics, such as non-steroid anti-inflammatory drugs and/or paracetamol, was permitted at the discretion of the investigator. Use of hormonal contraceptives is permitted.

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: IV-tracer EMI-137; IV-administration of EMI-137: all patients will receive 0.13 mg/kg of the fluorescent tracer EMI-137 intravenously.; Molecular Fluorescence Endoscopy: approximately 2,5 hours after tracer administration, Molecular Fluorescence Endoscopy will be performed with additional measurements of fluorescence signals.

Drug: IV-administation of EMI-137; Intravenous administration of 0.13 mg/kg of the fluorescent tracer EMI-137 approximately 2.5 hours prior to the endoscopy procedure.; Other Names: Tracer administation; Device: Molecular Fluorescence Endoscopy platform; A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working-channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the endoscopic resection, during the same endoscopy procedure.; Other Names: Fluorescence Endoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor-to-background ratio that allows the in vivo detection of (pre)malignant lesions in patients with Barrett's Esophagus using molecular fluorescence endoscopy.	Calculation of the in vivo tumor-to-background ratio (> 1.5) based on fluorescence intensities in (pre)malignant lesions compared to surrounding healthy esophageal tissue.	Day 1
Safety: the number of participants with symptoms or changes in vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to administration of EMI-137.		Up to day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
The correlation of fluorescence signals to histopathology from (pre)malignant lesions and surrounding normal esophageal tissue.	Up to 1 year
Identification of fluorescence lesions and correlation with histopathology on subsequent biopsies in the resection surface after endoscopic mucosal resection.	Up to 1 year
Quantification of fluorescence signals in vivo and ex vivo of (pre)malignant lesions and normal esophageal tissue using multi-diameter single-fiber reflectance single-fiber fluorescence (MDSFR-SFF) spectroscopy.	Up to 1 year
Visualization of the localization and distribution patterns of EMI-137 in the esophagus using ex vivo fluorescence microscopy.	Up to 1 year

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: G.M. van Dam, MD, PhD, University Medical Center Groningen; Principal Investigator: W.B. Nagengast, MD, PhD, PharmD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2017
• Primary Completion (Actual): March 25, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Esophagus; BE; EAC; HGD
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Barrett Esophagus
• Other Study ID Numbers: NL59628.042.16

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