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
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Feasibility of shortening qFME procedural time by oral administration of bevacizumab-800CW and cetuximab-800CW for the detection of BE neoplasia.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 T
- •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.
Arms & Interventions
Oral bevacizumab-800CW
Dose finding of oral bevacizumab-800CW and extend optimal dose group (n = 5 - 10)
Intervention: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy (Device)
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)
Intervention: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy (Device)
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)
Intervention: Fluorescence endoscopy and multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy (Device)
Oral bevacizumab-800CW
Dose finding of oral bevacizumab-800CW and extend optimal dose group (n = 5 - 10)
Intervention: Avastin (Drug)
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)
Intervention: Erbitux (Drug)
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)
Intervention: Erbitux (Drug)
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)
Intervention: Avastin (Drug)
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)
Intervention: Avastin (Drug)
Outcomes
Primary Outcomes
Feasibility of shortening qFME procedural time by oral administration of bevacizumab-800CW and cetuximab-800CW for the detection of BE neoplasia.
Time Frame: 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
Time Frame: 12 months
Increased lesion detection in % compared to previously gathered amount of invisible lesions with topical tracer administration
Secondary Outcomes
- To (semi)quantify and evaluate the in vivo fluorescent signal of bevacizumab-800CW and cetuximab-800CW(12 months)
- Eventually further specify and objectify the improvement of qFME by standardisation(12 months)
- Collect safety data on oral administration of (combined) bevacizumab-800CW and cetuximab-800CW.(Five minutes before and ten minutes after tracer administration)
- Heart rate(Five minutes before and ten minutes after tracer administration)
- Temperature(Five minutes before and ten minutes after tracer administration)
Investigators
dr. W.B. Nagengast, MD
Prof. Dr.
University Medical Center Groningen