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

Primary Purpose

Barrett Esophagus, Esophageal Cancer, Dysplasia in Barrett Esophagus

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
IV-administation of EMI-137
Molecular Fluorescence Endoscopy platform
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Barrett Esophagus focused on measuring BE, EAC, HGD, Esophagus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Medical Center Groningen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IV-tracer EMI-137

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

The correlation of fluorescence signals to histopathology from (pre)malignant lesions and surrounding normal esophageal tissue.
Identification of fluorescence lesions and correlation with histopathology on subsequent biopsies in the resection surface after endoscopic mucosal resection.
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.
Visualization of the localization and distribution patterns of EMI-137 in the esophagus using ex vivo fluorescence microscopy.

Full Information

First Posted
June 29, 2017
Last Updated
November 4, 2020
Sponsor
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT03205501
Brief Title
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions
Acronym
EAGLE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
February 9, 2017 (Actual)
Primary Completion Date
March 25, 2019 (Actual)
Study Completion Date
September 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
See brief summary.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Barrett Esophagus, Esophageal Cancer, Dysplasia in Barrett Esophagus
Keywords
BE, EAC, HGD, Esophagus

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV-tracer EMI-137
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IV-administation of EMI-137
Other Intervention Name(s)
Tracer administation
Intervention Description
Intravenous administration of 0.13 mg/kg of the fluorescent tracer EMI-137 approximately 2.5 hours prior to the endoscopy procedure.
Intervention Type
Device
Intervention Name(s)
Molecular Fluorescence Endoscopy platform
Other Intervention Name(s)
Fluorescence Endoscopy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tumor-to-background ratio that allows the in vivo detection of (pre)malignant lesions in patients with Barrett's Esophagus using molecular fluorescence endoscopy.
Description
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.
Time Frame
Day 1
Title
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.
Time Frame
Up to day 3
Secondary Outcome Measure Information:
Title
The correlation of fluorescence signals to histopathology from (pre)malignant lesions and surrounding normal esophageal tissue.
Time Frame
Up to 1 year
Title
Identification of fluorescence lesions and correlation with histopathology on subsequent biopsies in the resection surface after endoscopic mucosal resection.
Time Frame
Up to 1 year
Title
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.
Time Frame
Up to 1 year
Title
Visualization of the localization and distribution patterns of EMI-137 in the esophagus using ex vivo fluorescence microscopy.
Time Frame
Up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
W.B. Nagengast, MD, PhD, PharmD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
G.M. van Dam, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713GZ
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions

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