Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions

NCT03205501 | Completed Phase 1 DMC

• 1 other identifier: NL59628.042.16
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Barrett Esophagus; Esophageal Cancer; Dysplasia in Barrett Esophagus

Keywords

BE; EAC; HGD; Esophagus

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (1)

IV-tracer EMI-137

EXPERIMENTAL

* 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; Device: Molecular Fluorescence Endoscopy platform

Interventions

IV-administation of EMI-137 DRUG

Intravenous administration of 0.13 mg/kg of the fluorescent tracer EMI-137 approximately 2.5 hours prior to the endoscopy procedure.

Also known as: Tracer administation

IV-tracer EMI-137

Molecular Fluorescence Endoscopy platform DEVICE

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.

Also known as: Fluorescence Endoscopy

IV-tracer EMI-137

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

MeSH Terms

Conditions

Barrett Esophagus; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms

Study Officials

• W.B. Nagengast, MD, PhD, PharmD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• G.M. van Dam, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: July 2, 2017
• Study Start: February 9, 2017
• Primary Completion: March 25, 2019
• Study Completion: September 1, 2019
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)