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

Sponsor

University Medical Center Groningen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05745857

Collaborator

(none)

Enrollment

Location

Arms

19.1

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Barrett's Esophagus Without Dysplasia Barrett Oesophagitis With Dysplasia Esophageal Adenocarcinoma	Drug: Avastin Drug: Erbitux Device: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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 Drug: Erbitux Orally administered Other Names: Cetuximab 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: 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 Drug: Erbitux Orally administered Other Names: Cetuximab 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

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

Drug: Erbitux

Orally administered

Other Names:

Cetuximab

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: 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

Drug: Erbitux

Orally administered

Other Names:

Cetuximab

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

Outcome Measures

Primary Outcome Measures

Feasibility of shortening qFME procedural time by oral administration of bevacizumab-800CW and cetuximab-800CW for the detection of BE neoplasia. [12 months]
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
Evaluate if the combination of tracers improves lesion detection by the number of invisible lesions detected [12 months]
Increased lesion detection in % compared to previously gathered amount of invisible lesions with topical tracer administration

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.