Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions

Phase 1

Completed

Conditions: Barrett Esophagus
Dysplasia in Barrett Esophagus
Esophageal Cancer

Interventions: Drug: IV-administation of EMI-137
Device: Molecular Fluorescence Endoscopy platform

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
IV-tracer EMI-137	IV-administation of 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.
IV-tracer EMI-137	Molecular Fluorescence Endoscopy platform	* 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.

Primary Outcome Measures

Name	Time	Method
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
Tumor-to-background ratio that allows the in vivo detection of (pre)malignant lesions in patients with Barrett's Esophagus using molecular fluorescence endoscopy.	Day 1	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.

Secondary Outcome Measures

Name	Time	Method
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
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
Visualization of the localization and distribution patterns of EMI-137 in the esophagus using ex vivo fluorescence microscopy.	Up to 1 year

Locations (1): University Medical Center Groningen
🇳🇱
Groningen, Netherlands