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

University Medical Center Groningen (UMCG)

Status and phase: Not yet enrolling; Phase 2

Conditions: Barrett's Esophagus Without Dysplasia; Barrett Oesophagitis With Dysplasia; Esophageal Adenocarcinoma

Treatments: Drug: Avastin; Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy; Drug: Erbitux

Study type: Interventional

Funder types: Other

Identifiers

NCT05745857

16054

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

Oral bevacizumab-800CW

Experimental group

Description:

Dose finding of oral bevacizumab-800CW and extend optimal dose group (n = 5 - 10)

Treatment:

Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy

Drug: Avastin

Oral cetuximab-800CW and combined oral cetuximab-800CW and bevacizumab-800CW

Experimental group

Description:

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)

Treatment:

Drug: Erbitux

Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy

Drug: Avastin

Combined topical tracer administration bevacizumab-800CW and cetuximab-800CW

Experimental group

Description:

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)

Treatment:

Drug: Erbitux

Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy

Drug: Avastin