Detection of Early Esophageal Cancer by NIR-FME.

Phase 2

• Conditions: Barrett Esophagus
• Interventions: Drug: Bevacizumab-IRDye800CW; Diagnostic Test: Fluorescence endoscopy

• Registration Number: NCT03877601
• Lead Sponsor: University Medical Center Groningen

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-02-27
• Study First Submitted QC: 2019-03-14
• Study First Posted: 2019-03-15
• Study Start: 2019-07-29
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-04
• Primary Completion: 2021-09-01
• Study Completion: 2021-10-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Topical administration of bevacizumab-800CW	Bevacizumab-IRDye800CW	The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform).
Topical administration of bevacizumab-800CW	Fluorescence endoscopy	The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands