Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophagitis

Barrett Esophagus

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Esophageal Diseases

Gastrointestinal Diseases

Gastroenteritis

Precancerous Conditions

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Cetuximab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

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

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)

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)

Avastin

Erbitux

Fluorescent endoscope fiber and spectroscopy probe will be inserted through the working channel of the normal clinical therapeutic endoscope

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

Wouter B Nagengast, Prof. dr.

Wouter B Nagengast, Prof.

Wouter B. Nagengast, Prof. dr.

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.

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.

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.

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

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

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

Increased lesion detection in % compared to previously gathered amount of invisible lesions with topical tracer administration

Blood pressure in millimeters of mercury (mmHg)

Correlate and validate fluorescence signals detected in vivo with ex vivo histopathology grade of dysplasia and VEGFA and EGFR expression

Determining optimal pre-set features for gain and exposure times for our fluorescence camera system

University Medical Center Groningen

Prof. Dr.

Symptoms and General Pathology

Recurrence

Pharmaceutical Solutions

Anti-Infective Agents

Itraconazole

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Participants in this arm will receive the capsule form of itraconazole

Participants in this arm will receive the solution form of itraconazole

Patients with high-risk BE will receive two weeks of itraconazole in the capsule form (N=5).

Itraconazole in capsule form

Patients with high-risk BE will receive two weeks of itraconazole in the solution form (N=5).

Itraconazole in solution form

Jill Torneden

Ajay Bansal

Recurrent Barrett's esophagus (BE) that occurs at the rate of 12.4%/year is the Achilles heel of the endoscopic treatment of high-risk BE. Over time, after eradication, BE ultimately recurs in as many as 30-50% of the patients putting them at risk for esophageal adenocarcinoma (EAC), thereby undoing the benefits of an effective initial therapy. Also, recurrences need retreatments that increase costs and complications including strictures and refractory ulcerations. A therapy to prevent recurrent BE does not currently exist. Itraconazole with its ability to inhibit important molecular pathways related to BE development could enhance the long-term effectiveness of endoscopic eradication of high-risk BE, thereby promoting a long-term cure

The primary purpose is to determine the ideal formulation (capsule versus solution) of itraconazole in this short-term pilot study.

Itraconazole to Prevent Recurrent Barrett's Esophagus

Itraconazole Repurposing to Reduce Residual Cancer Risk in Patients With High-risk Barrett's Esophagus After Ablation

The primary endpoint will be the tissue (in esophageal biopsies) and blood concentrations of itraconazole.

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Reduction in Vascular endothelial growth factor (VEGF)/ Vascular endothelial growth factor receptor type 2 (VEGFR2) by IHC

University of Texas, Southwestern Medical Center at Dallas

University of Kansas Medical Center

Metaplasia

Micronutrients

Vitamins

Acetic Acid

Retinol acetate

Vitamin A

Retinol palmitate

Anti-Bacterial Agents

Adjuvants, Immunologic

Immunologic Factors

Protective Agents

Retinol

* Patients with known Barrett's metaplasia under surveillance
* Patients with Barrett's metaplasia who had undergone endoscopic treatment for neoplasia previously and were under surveillance for metachronous neoplasia
* Patients suspected of neoplasia referred for endoscopic mucosal resection or other targeted endoscopic treatment of the lesion

Prospective observational pilot study.

We would examine patients with Barrett's epithelium that is either healthy or has suspected areas of neoplasia. We will apply acetic acid spray to areas of healthy Barrett's metaplasia and time how long it takes for the aceto whitening to disappear. We will repeat this in cases referred with SM invasive cancer, intramucosal cancer, suspected high grade dysplasia and possible low grade dysplasia. We will record how long it takes for the acetowhitening to disappear. We will biopsy these areas to confirm the diagnosis.

We will correlate the histology to the aceto-whitening time to see if there is a correlation between the degree of neoplasia and the aceto-whitening time after acetic acid dye spray.

Acetic acid chromoendoscopy

Gaius Longcroft-Wheaton, MD, MRCP

Pradeep Bhandari, MD, FRCP

Acetic acid chromoendoscopy is an established standard technique used to detect dysplasia within the gastrointestinal tract. Acetic acid spray helps to identify neoplasia by highlighting the surface pattern, highlighting the vascular pattern and by a process known as the aceto-whitening reaction, where tissues take acetic acid and turn white for a brief period and then slowly revert back to a normal colour. The neoplastic surface and vascular pattern are all very well described, and have played a big role in the recognition of early cancer. The aceto-whitening reaction is well described but the differential in timing between neoplastic and non-neoplastic areas is not well understood.

The investigators aim to establish the differential in the timing of the disappearance of the aceto-whitening reaction between healthy tissue, dysplastic tissue, intramucosal cancer and invasive cancer after acetic acid dye spray in the oesophagus and colon. By understanding this better, the investigators may be able to predict with greater accuracy whether a highlighted abnormal area is cancer or high grade dysplasia, or whether it is low grade dysplasia or inflammation, which has significant prognostic implications for the patient.

The investigators hypothesize that the differential in the timing of the disappearance of the aceto-whitening reaction between normal and abnormal tissue could help in the detection of gastrointestinal neoplasia.

This is a prospective pilot study. It is standard practice within our unit to use acetic acid for the detection of neoplasia. No patient would receive any additional intervention that would not normally be performed.

We will record the surface and vascular patterns before and after acetic acid spray. As usual we will then apply acetic acid spray to the Barrett's epithelium and time how long it takes for the aceto whitening to disappear. It is the timing of the disappearance that is the key study intervention. We will biopsy these areas to confirm the diagnosis. Again this is standard practice and no patient will be denied an intervention that is normally performed, and no extra interventions will be performed over and above the standard clinical practice.

We will correlate the histology to the aceto-whitening disappearance time to identify a threshold time which can serve as a cut off between neoplastic and non-neoplastic tissue.

We hypothesise that the aceto-whitening reaction lasts much longer in the normal epithelium of Barrett's oesophagus and colon. This reaction will be much shorter in areas with abnormal pathology like dysplasia or cancer.

Only pathology retained is for NHS purposes only. No separate tissue retained for the study

Aceto-whitening in the Assessment of Gastrointestinal Neoplasia

Acetowhitening Time as a Novel Objective Tool for the Diagnosis of High Risk Neoplasia in Barrett's Oesophagus

To quantify the differential in the timing of the disappearance of the aceto-whitening reaction between metaplastic tissue, dysplastic tissue and invasive cancer after acetic acid dye spray in the oesophagus and colon.

To differentiate high grade displasia and intramucosal cancer from invasive cancer using the aceto-whitening timing

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oral Bevacizumab-800CW and Cetuximab-800CW Administration to Detect Early Esophageal Adenocarcinomas	NCT05745857	Barrett's Esoph... Barrett Oesopha... Esophageal Aden...	Avastin Erbitux Fluorescence en...	18 Years -	University Medical Center Groningen
Itraconazole to Prevent Recurrent Barrett's Esophagus	NCT05609253	Barrett Oesopha...	Itraconazole in... Itraconazole in...	18 Years -	University of Kansas Medical Center
Aceto-whitening in the Assessment of Gastrointestinal Neoplasia	NCT01618643	Barrett Esophag... Barrett Metapla... Barrett Oesopha... Barrett Adenoca...	Acetic acid chr...	18 Years -	Portsmouth Hospitals NHS Trust
Oral Bevacizumab-800CW and Cetuximab-800CW Administration to Detect Early Esophageal Adenocarcinomas	NCT05745857	Barrett's Esoph... Barrett Oesopha... Esophageal Aden...	Avastin Erbitux Fluorescence en...	18 Years -	University Medical Center Groningen
Aceto-whitening in the Assessment of Gastrointestinal Neoplasia	NCT01618643	Barrett Esophag... Barrett Metapla... Barrett Oesopha... Barrett Adenoca...	Acetic acid chr...	18 Years -	Portsmouth Hospitals NHS Trust

Spots Global Cancer Trial Database for barrett oesophagitis with dysplasia