Detection of Early Esophageal Cancer by NIR-FME. (ESCEND)

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

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.

Study Overview

• Status: Unknown
• Conditions: Barrett Esophagus
• Intervention / Treatment: Drug: Bevacizumab-IRDye800CW; Diagnostic test: Fluorescence endoscopy

Detailed Description

See brief summary

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Topical administration of bevacizumab-800CW; The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform).

Drug: Bevacizumab-IRDye800CW; Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.; Diagnostic test: Fluorescence 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Helmholtz Zentrum München
• Investigators: Principal Investigator: Vasilis Ntziachristos, Prof. Dr., Helmholtz Zentrum München

Publications and helpful links

General Publications

• Nagengast WB, Hartmans E, Garcia-Allende PB, Peters FTM, Linssen MD, Koch M, Koller M, Tjalma JJJ, Karrenbeld A, Jorritsma-Smit A, Kleibeuker JH, van Dam GM, Ntziachristos V. Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A. Gut. 2019 Jan;68(1):7-10. doi: 10.1136/gutjnl-2017-314953. Epub 2017 Dec 15. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Endoscopy; Fluorescence; Bevacizumab-800CW
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Precancerous Conditions; Esophageal Neoplasms; Barrett Esophagus; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: NL68582.042.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No