Detection of Early Esophageal Cancer by NIR-FME.

Study Overview
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Brief Summary
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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 Vascular Endothelial Growth Factor (VEGF) is overexpressed in dysplastic and neoplastic areas in BE segments versus normal tissue and has proven to be a valid target for molecular imaging. The University Medical Center Groningen (UMCG) developed a fluorescent tracer by labeling the VEGF-targeting humanized monoclonal antibody bevacizumab, currently used in anti-cancer therapy, with the fluorescent dye IRDye800CW. The phase I study, named VICE, completed within the UMCG, showed that synchronal use of VEGFA-guided near-infrared fluorescence molecular endoscopy (NIR-FME) and high-definition white light endoscopy (HD-WLE), following topical or systemic tracer administration, could be practiced to recognize dysplastic and early EAC lesions in patients with BE. Furthermore, early lesion detection was improved by  33% using the topically applied tracer approach compared with HD-WL/NBI endoscopy. With this phase 2 intervention study the investigators aim to statistically confirm previous pilot (Phase I) clinical data showing that the combination of HD-WLE and FME using labelled bevacizumab improves early EC detection over the current clinical standard.

Detailed Description
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See brief summary

Official Title
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A Prospective Follow-up Intervention Study: Detection of Early Esophageal Cancer by Near-infrared Fluoresence Molecular Endoscopy Using Bevacizumab-800CW

Conditions
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Barrett Esophagus

Intervention / Treatment
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* Drug: Bevacizumab-IRDye800CW
* Diagnostic Test: Fluorescence endoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspicion or diagnosed LGD, HGD or superficial EAC and planned diagnostic and/or therapeutic endoscopy. Age: 18 years or older. Written informed consent. Exclusion Criteria: Patients younger than 18 years old Submucosal and invasive EAC; EAC with TNM-classification other than T1. Radiation therapy for esophageal cancer Immunoglobulin allergy Chemotherapy, immunotherapy or surgery 28 days before administration of the tracer Prior Bevacizumab treatment Non-adjustable hypertension Medical or psychiatric conditions that compromise the patient's ability to give informed consent. Pregnancy or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical administration of bevacizumab-800CW<br>The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform). | Drug: Bevacizumab-IRDye800CW<br>* Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.<br>Diagnostic Test: Fluorescence endoscopy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescence signal in patients with Barrett's Esophagus | Evaluating the performance of FME with topical administration of Bevacizumab-800CW for detection of neoplasia in BE patients compared to HD-WLE to make an estimation of the diagnostic accuracy in terms of sensitivity and specificity in order to make a power size calculation for the Phase III trial. | During the endoscopic procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex vivo fluorescence singals | Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGF expression | 2 years | 
| Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR). | Data collection as a measure of safety and tolerability regarding administration of Bevacizumab-IRDye800CW | Up to 1 week after administration of tracer | 
| Interrogate potential new EC biomarkers | We will perform ex-vivo binding experiments with tracers against GREM1, -SULF1 and -PRKCi on the fresh EMR if available and compare them against the in-vivo WLE/NIR-FME findings. We will analyze the sensitivity and specificity of the novel markers alone or in combination. The targeting moieties will be coupled with different fluorophores allowing for multi-parametric analysis. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluorescence, Endoscopy, Bevacizumab-800CW