Detection of Early Esophageal Cancer by NIR-FME.

NCT03877601 | Unknown Phase 2 DMC

• 1 other identifier: NL68582.042.18
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Barrett Esophagus

Keywords

Fluorescence; Endoscopy; Bevacizumab-800CW

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Ex vivo fluorescence singals

  2 years

• 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

• Interrogate potential new EC biomarkers

  2 years

Study Arms (1)

Topical administration of bevacizumab-800CW

EXPERIMENTAL

The tracer will be topically administered 5 minutes prior to the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform).

Drug: Bevacizumab-IRDye800CW; Diagnostic Test: Fluorescence endoscopy

Interventions

Bevacizumab-IRDye800CW DRUG

Topical administration of Bevacizumab-IRDye800CW during the endoscopic procedure.

Topical administration of bevacizumab-800CW

Fluorescence endoscopy DIAGNOSTIC_TEST

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.

Topical administration of bevacizumab-800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Suspicion or diagnosed LGD, HGD or superficial EAC and planned diagnostic and/or therapeutic endoscopy.
• Age: 18 years or older.
• Written informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Helmholtz Zentrum München: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 29247063 BACKGROUND

MeSH Terms

Conditions

Barrett Esophagus

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• W.B. Nagengast, MD, PhD, PharmD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Vasilis Ntziachristos, Prof. Dr.

  Helmholtz Zentrum München

  PRINCIPAL INVESTIGATOR

Central Study Contacts

W.B. Nagengast, MD, PhD, PharmD

CONTACT

+31503612620; w.b.nagengast@umcg.nl

R.Y. Gabriels, MSc, MD

CONTACT

+31615691998; r.y.gabriels@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: February 27, 2019
• First Posted: March 15, 2019
• Study Start: July 29, 2019
• Primary Completion: September 1, 2021
• Study Completion: October 1, 2021
• Last Updated: November 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)