Clinical trial NCT03205501: Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Barrett Esophagus
Esophageal Cancer
Dysplasia in Barrett Esophagus
Keywords: BE
EAC
HGD
Esophagus
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Primary outcomes:
measure: Tumor-to-background ratio that allows the in vivo detection of (pre)malignant lesions in patients with Barrett's Esophagus using molecular fluorescence endoscopy.
timeFrame: Day 1
measure: 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.
timeFrame: Up to day 3
Secondary outcomes:
measure: The correlation of fluorescence signals to histopathology from (pre)malignant lesions and surrounding normal esophageal tissue.
timeFrame: Up to 1 year
measure: Identification of fluorescence lesions and correlation with histopathology on subsequent biopsies in the resection surface after endoscopic mucosal resection.
timeFrame: Up to 1 year
measure: 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.
timeFrame: Up to 1 year
measure: Visualization of the localization and distribution patterns of EMI-137 in the esophagus using ex vivo fluorescence microscopy.
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: W.B. Nagengast, MD, PhD, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: G.M. van Dam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: