Barrett Esophagus
Conditions
Keywords
Fluorescence, Endoscopy, Bevacizumab-800CW
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 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
See brief summary
Interventions
Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.
DIAGNOSTIC_TESTFluorescence endoscopy
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.
Sponsors
Helmholtz Zentrum München
University Medical Center Groningen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluorescence signal in patients with Barrett's Esophagus | During the endoscopic procedure | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ex vivo fluorescence singals | 2 years | Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGF expression |
| Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR). | Up to 1 week after administration of tracer | Data collection as a measure of safety and tolerability regarding administration of Bevacizumab-IRDye800CW |
| Interrogate potential new EC biomarkers | 2 years | 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. |
Countries
Netherlands
Contacts
Primary ContactW.B. Nagengast, MD, PhD, PharmD
Backup ContactR.Y. Gabriels, MSc, MD
Outcome results
None listed