Oral Bevacizumab-800CW and Cetuximab-800CW Administration to Detect Early Esophageal Adenocarcinomas (SLURP)

A Phase 2 Intervention Study: Detection of Early Esophageal Neoplastic Lesions by Quantified Fluorescence Molecular Endoscopy Using Oral and Topical Administration of Bevacizumab-800CW and Cetuximab-800CW

Previous studies have confirmed the great potential of quantitative fluorescence molecular endoscopy (qFME) when looking at additional lesion detection initially missed by high-definition white light endoscopy (HD-WLE) for surveillance of Barrett's esophagus.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Adenocarcinoma; Barrett's Esophagus Without Dysplasia; Barrett Oesophagitis With Dysplasia
• Intervention / Treatment: Drug: Avastin; Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy; Drug: Erbitux

Detailed Description

However, the investigators hypothesized, that additional lesions can potentially be identified by simultaneous use of two targeted tracers because of variable expression of vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR )within oesophageal adenocarcinoma (EAC). Until now, solely intravenous and topical administration of the tracers has been investigated. However, optimization of tracer administration and shortened incubation is necessary for clinical translation and implementation of this new technique from Barrett's esophagus (BE) expert centers to regional non-expert centers. BE surveillance procedures normally takes up to 15 minutes at regional hospitals, of which most of the procedural time is needed to take biopsies according to the Seattle protocol. Introducing qFME into these hospitals would elongate the procedure time with at least 10 - 15 minutes. This would increase healthcare costs and put increased pressure on BE healthcare. Ideally, the gastroenterologist can immediately start with the qFME procedure without any incubation time while maintaining the best target-to-background ratios (TBR) possible. Oral administration by drinking the tracer prior to the procedure would eliminate incubation time and its consequences. Quantified qFME with oral tracer administration and targeted biopsies could potentially replace the time-consuming, high miss rate Seattle protocol, improve lesion detection and decrease global healthcare costs associated with BE.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wouter B Nagengast, Prof. dr.; Phone Number: +31(0)503615755; Email: w.b.nagengast@umcg.nl

Study Locations

• Netherlands
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands, 9713 GZ
      • Recruiting
      • University Medical Center Groningen
      • Contact: Wouter B Nagengast, Prof.; Phone Number: +31(0)503615755; Email: w.b.nagengast@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BE patients without dysplasia and with suspected/diagnosed low-grade dysplasia (LGD), high-grade dysplasia (HGD) or superficial EAC and planned diagnostic and/or therapeutic endoscopy
• Written informed consent is obtained

Exclusion Criteria:

• Patients under the age of eighteen.
• Submucosal and invasive EAC, also defined as EAC with tumor, node and metastasis (TNM)-classification other than T1.
• Previous radiation therapy for esophageal cancer
• Known immunoglobulin allergy
• Previous chemotherapy, immunotherapy or related surgery
• Prior bevacizumab or cetuximab treatment
• 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: Prevention
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral bevacizumab-800CW; Dose finding of oral bevacizumab-800CW and extend optimal dose group (n = 5 - 10)	Drug: Avastin; Orally administered; Other Names: Bevacizumab; Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy; Fluorescent endoscope fiber and spectroscopy probe will be inserted through the working channel of the normal clinical therapeutic endoscope
Experimental: Oral cetuximab-800CW and combined oral cetuximab-800CW and bevacizumab-800CW; Dose finding of oral cetuximab-800CW in first five patients and combined oral bevacizumab-800CW and cetuximab-800CW if the investigators see good results with cetuximab-800CW. If not, they will add a control group of non-dysplastic BE patients and administer oral bevacizumab-800CW. (n = 15)	Drug: Avastin; Orally administered; Other Names: Bevacizumab; Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy; Fluorescent endoscope fiber and spectroscopy probe will be inserted through the working channel of the normal clinical therapeutic endoscope; Drug: Erbitux; Orally administered; Other Names: Cetuximab
Experimental: Combined topical tracer administration bevacizumab-800CW and cetuximab-800CW; This arm will only be part of the study when oral administration is not feasible or safe. Compare single topical tracer administration of bevacizumab-800CW with combined topical tracer administration of bevacizumab-800CW and cetuximab-800CW. Extend combined group when lesion detection is increased or add control group with non-dysplastic BE patients if not. (n = 20)	Drug: Avastin; Orally administered; Other Names: Bevacizumab; Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy; Fluorescent endoscope fiber and spectroscopy probe will be inserted through the working channel of the normal clinical therapeutic endoscope; Drug: Erbitux; Orally administered; Other Names: Cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of shortening qFME procedural time by oral administration of bevacizumab-800CW and cetuximab-800CW for the detection of BE neoplasia.	Evaluating the performance of qFME with oral administration of bevacizumab-800CW and cetuximab-800CW for detection of neoplasia in BE patients compared to HD-WLE. This comparison will be based on target-to-background rations calculated from the in vivo fluorescence images and quantified by MDSFR/SFF spectroscopy measurements	12 months
Evaluate if the combination of tracers improves lesion detection by the number of invisible lesions detected	Increased lesion detection in % compared to previously gathered amount of invisible lesions with topical tracer administration	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collect safety data on oral administration of (combined) bevacizumab-800CW and cetuximab-800CW.	Blood pressure in millimeters of mercury (mmHg)	Five minutes before and ten minutes after tracer administration
Heart rate	Beats per minute	Five minutes before and ten minutes after tracer administration
Temperature	Degrees Celsius	Five minutes before and ten minutes after tracer administration
To (semi)quantify and evaluate the in vivo fluorescent signal of bevacizumab-800CW and cetuximab-800CW	Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGFA and EGFR expression	12 months
Eventually further specify and objectify the improvement of qFME by standardisation	Determining optimal pre-set features for gain and exposure times for our fluorescence camera system	12 months

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Wouter B. Nagengast, Prof. dr., University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 2, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): February 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Esophageal adenocarcinoma; Spectroscopy; Barrett's esophagus; Fluorescence molecular endoscopy
• Additional Relevant MeSH Terms: Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Barrett Esophagus; Adenocarcinoma Of Esophagus; Amino Acids, Peptides, and Proteins; Proteins; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chemistry Techniques, Analytical; Bevacizumab; Cetuximab; Spectrum Analysis
• Other Study ID Numbers: 16054

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
• product manufactured in and exported from the U.S.: No