Clinical trial NCT05745857: Oral Bevacizumab-800CW and Cetuximab-800CW Administration to Detect Early Esophageal Adenocarcinomas
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Barrett's Esophagus Without Dysplasia
Barrett Oesophagitis With Dysplasia
Esophageal Adenocarcinoma
Keywords: Fluorescence molecular endoscopy
Spectroscopy
Barrett's esophagus
Esophageal adenocarcinoma
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2023-02-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Arm 1: Oral bevacizumab-800CW If oral administration is feasible the investigators will move on to arm 2, if it does not seem feasible the investigators will move on to arm 3.

Arm 2: Oral cetuximab-800CW The investigators will move on to combined oral bevacizumab-800CW/cetuximab-800CW if oral cetuximab-800CW seems feasible. If it does not seem feasible, they will administer oral bevacizumab-800CW to a control group of non-dysplastic Barrett's esophagus patients.

Arm 3 (only performed if oral administration does not work) Topical administration of bevacizumab-800CW compared to combined topical administration of bevacizumab-800CW/cetuximab-800CW. This group will be expanded if combined administration increases lesion detection. If this is not the case, the investigators will include a control group of non-dysplastic patients with Barrett's esophagus as a control group who will receive topical bevacizumab-800CW.
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility of shortening qFME procedural time by oral administration of bevacizumab-800CW and cetuximab-800CW for the detection of BE neoplasia.
timeFrame: 12 months
measure: Evaluate if the combination of tracers improves lesion detection by the number of invisible lesions detected
timeFrame: 12 months
Secondary outcomes:
measure: Collect safety data on oral administration of (combined) bevacizumab-800CW and cetuximab-800CW.
timeFrame: Five minutes before and ten minutes after tracer administration
measure: Heart rate
timeFrame: Five minutes before and ten minutes after tracer administration
measure: Temperature
timeFrame: Five minutes before and ten minutes after tracer administration
measure: To (semi)quantify and evaluate the in vivo fluorescent signal of bevacizumab-800CW and cetuximab-800CW
timeFrame: 12 months
measure: Eventually further specify and objectify the improvement of qFME by standardisation
timeFrame: 12 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Wouter B. Nagengast, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: