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

Esophageal Adenocarcinoma Clinical Trial

— SLURP  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05745857
• Other study ID #: 16054
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2023
• Est. completion date: December 2024

Study information

• Verified date: February 2023
• Source: University Medical Center Groningen
• Contact: Wouter B Nagengast, Prof. dr.
• Phone: +31(0)503615755
• Email: w.b.nagengast[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Barrett Esophagus
• Barrett Oesophagitis With Dysplasia
• Barrett's Esophagus Without Dysplasia
• Esophageal Adenocarcinoma
• Esophageal Neoplasms
• Esophagitis

Intervention

Drug:
• Avastin
Orally administered
• Erbitux
Orally administered

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

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Heart rate	Beats per minute	Five minutes before and ten minutes after tracer administration
Secondary	Temperature	Degrees Celsius	Five minutes before and ten minutes after tracer administration
Secondary	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
Secondary	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