Condition category
Cancer
Date applied
12/06/2017
Date assigned
25/07/2017
Last edited
16/10/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Ms Michele Bianchi

ORCID ID

Contact details

MRC Cancer Centre
Hutchison MRC Research Centre
University of Cambridge
Cambridge
CB2 0XZ
United Kingdom

Type

Scientific

Additional contact

Dr Massimiliano di Pietro

ORCID ID

Contact details

MRC Cancer Centre
Hutchison MRC Research Centre
University of Cambridge
Cambridge
CB2 0XZ
United Kingdom
+44 122 3763994
md460@mrc-cu.cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

33291

Study information

Scientific title

Cross-over randomised study to evaluate the combination of autofluorescence imaging and confocal laser endomicroscopy to diagnose dysplasia in Barrett’s oesophagus

Acronym

Study hypothesis

The aim of this study is to test a combination of enhanced endoscopic imaging (autofluorescence imaging and confocal laser endomicroscopy) in combination to molecular tests on tissue samples to allow diagnosis of dysplasia and early cancer in Barrett’s oesophagus.

Ethics approval

East of England - Cambridgeshire and Hertfordshire Research Ethic Committee, 05/04/2017, ref: 16/EE/0554

Study design

Randomised; Interventional; Design type: Diagnosis, Imaging

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Gastroenterology, Primary sub-specialty: Gastroenterology; UKCRC code/ Disease: Oral and Gastrointestinal/ Other diseases of the digestive system, Cancer/ Malignant neoplasms of digestive organs

Intervention

As part of this study, patients referred with flat Barrett’s oesophagus without evidence of visible lesions receive two endoscopies in a randomised order (standard procedure and experimental procedure).

Standard procedure: This includes a standard endoscopy with multiple random biopsies according to the Seattle protocol (targeted biopsies on visible lesions + 4 biopsies every 2 cm within the Barrett's oesophagus). The endoscopist is only be allowed to use white light high resolution endoscopy.

Experimental procedure: This procedure uses multimodal imaging. The endoscopist uses autofluorescence imaging (AFI) to identify area at risk of dysplasia. These are analysed with Probed-Based Confocal Laser Endomicrosopy (pCLE) to make a real-time optical diagnosis (Barrett’s with or without dysplasia). Two targeted biopsies stored in formalin are then taken for histology and biomarkers from each AFI targeted location. In patients with no AFI positive areas one random location are used for pCLE analysis and molecular biomarkers for every 5cm of maximum extent of the Barrett’s. The biopsies on AFI targeted areas processed for standard histology are used for clinical purpose as well and are part of the final histologic diagnosis and potentially inform treatment as per clinical guidelines.

In addition to histological diagnosis, the biopsies taken during the experimental procedure are tested for a panel of 3 molecular biomarkers.

After the first study procedure, the patient arecheduled for a second endoscopy 8-12 weeks after with the alternative protocol.

With the second procedure the patient completes the study and referred for standard clinical management based on the histopathological result of the biopsies taken during the two study procedures.

Intervention type

Other

Phase

Drug names

Primary outcome measures

The diagnostic accuracy for any grade of dysplasia of pCLE is measured comparing real-time optical diagnosis of dysplasia by pCLE on AFI-positive areas (experimental procedure) with the gold standard histologic diagnosis (overall pathological diagnosis from experimental and standard procedures).

Secondary outcome measures

1. Added value of the use of molecular biomarkers to the optical biopsy for the diagnosis of any grade of dysplasia. This will be measured by testing molecular biomarkers on tissue biopsies. The biomarkers result will be integrated with that of the optical diagnosis and the results will be compared with that of the gold standard histologic diagnosis.
2. Diagnostic accuracy for any grade of dysplasia of a panel of biomarkers performed on AFI-targeted biopsies. This will be measured by testing molecular biomarkers on tissue biopsies and comparing the results with the gold standard histologic diagnosis
3. Time to perform AFI-targeted pCLE vs gold standard (Seattle protocol). This will be measured as time from the beginning to the end of each endoscopic procedure. Standard and experimental procedure time will be compared.
4. Costs to perform AFI-targeted pCLE +/- biomarkers and conventional endoscopic surveillance with Seattle protocol. This will be measured by the costs of a single use of pCLE probe and laboratory costs of molecular biomarkers for the experimental procedure and costs for processing biopsies and costs of pathology time for histologic diagnosis for the standard procedure.
5. Patient-reported experience and outcome measures, including acceptability and anxiety levels. This outcome will be measured using 2 validated questionnaires: a 10-point visual analogue scale (VAS, 0 = worst and 10 = best), filled by participants before and after each procedure and 6-item state-trait anxiety inventory (STAI -6), completed after each procedure.

Overall trial start date

02/05/2017

Overall trial end date

31/12/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Able to read, comprehend, and complete the consent form
2. Aged ≥18
3. Diagnosed with dysplastic or non-dysplastic BO at least 2 cm in length if circumferential (C2) or 3 cm if not circumferential (M3)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 146; UK Sample Size: 146

Participant exclusion criteria

1. Oesophagitis (Los Angeles grade ≥B)
2. Previous oesophagectomy or known oesophageal abnormality (e.g. fistula or severe oesophageal stricture)
3. Previous evidence of oesophageal adenocarcinoma
4. Previous history of endoscopically visible BO-related neoplasia
5. Known allergy to fluorescein
6. Severe or uncontrolled asthma
7. Coagulopathy or anticoagulant/antiplatelet therapy for high risk conditions
8. Active or severe cardiopulmonary disease or decompensated liver disease
9. Pacemaker or other intra-cardiac electric device

Recruitment start date

02/05/2017

Recruitment end date

01/10/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cambridge University Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Nottingham University Hospital
The Queen's Medical Centre Campus Derby Road
Nottingham
NG7 2UH
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Presentation of final results in international conferences of gastroenterology in 2019. Planned publication in a high-impact peer reviewed journal by mid 2020

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from from the Chief Investigator, Dr Massimiliano di Pietro [md460@mrc-cu.cam.ac.uk ]

Intention to publish date

30/06/2020

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

13/10/2017: Cancer Help UK lay summary link added to plain English summary field 11/08/2017: Internal review.