The Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia

NCT04155242 | Recruiting DMC

• 1 other identifier: ISRCTN12730505
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective cohort study aims to assess the utility of a panel of molecular biomarkers for predicting the risk of relapse of Barrett's Oesophagus after endoscopic treatment of early oesophageal neoplasia with RadioFrequency Ablation (RFA). Patients who received endoscopic treatment of early oesophageal neoplasia with RFA and achieved endoscopic remission will be recruited. During the surveillance visits patients will receive a Cytosponge test followed by an endoscopy with Narrow Band Imaging (NBI) magnification and biopsies. Patients will receive an endoscopy every 6 months and Cytosponge every 12 months for at least 2 years. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples. After 2 years of intensive endoscopic follow up, patients will be prospectively tracked for up to 3 years. The investigators will also evaluate:

• The risk of progression to dysplasia or oesophageal intestinal metaplasia (IM) in patients with IM at the GOJ post RFA in the absence of retreatment
• the diagnostic accuracy of NBI for IM/dysplasia at the GOJ .

Conditions

Barrett's Oesophagus

Keywords

Barrett's oesophagus; Radiofrequency ablation; Early Oesophageal Neoplasia

Outcome Measures

Primary Outcomes (1)

• Diagnostic accuracy of methylation panel for diffuse IM at the GOJ

  Diagnostic accuracy of a panel of methylation markers (ZNF345, ZNF569 and TFPI2 loci) for diffuse IM at the GOJ assessed by Methylight on DNA extracted from GOJ biopsies (separately random and targeted biopsies) and Cytosponge samples.

  5 years

Secondary Outcomes (4)

• Proportion of patients developing true BE recurrence

  5 years

• Biomarker score for BE recurrence

  5 years

• Accuracy of Light Blue Crest sign

  5 years

• Safety of Cytosponge

  5 years

Study Arms (1)

Study group

EXPERIMENTAL

As part of the post RFA treatment follow up patients will receive a Cytosponge test followed by an endoscopy with NBI magnification and biopsies. Four endoscopies will be performed during 2 years of active follow up together with up to 2 Cytosponge procedures. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples obtained during the examinations will be assessed. Patients will be then followed up for up to 3 years with standard endoscopy to assess for relapse of Barrett's oesophagus/IM/dysplasia.

Diagnostic Test: Cytosponge test; Diagnostic Test: Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation; Diagnostic Test: Oesophagogastroduodenoscopy

Interventions

Cytosponge test DIAGNOSTIC_TEST

The Cytosponge will be administered by the study nurse prior to the participant having the endoscopy, usually as part of the same visit to hospital. The capsule along with the string is swallowed by drinking a small glass of water. The participant is asked to hold the Cytosponge in situ for 5 minutes. The sponge contained within expands and is then drawn back by the research nurse up the oesophagus by the attached string, collecting cells as it moves upwards. This device received a letter of no objection by the MHRA for use in the BEST pilot trial (LRQ 0939857) but it is not CE marked. Cytosponge and research endoscopic biopsies will be couriered to the Fitzgerald laboratory, at the MRC Cancer Cell Unit on a regular basis. The specimens will be processed in conjunction with the Cambridge University Hospitals' NHS Foundation Trust tissue bank which is accredited to GLP standards.

Study group

Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation DIAGNOSTIC_TEST

Molecular analysis of the specimen obtained by Cytosponge or endoscopic biopsies - TFF3 protein expression, methylation panel, p53 mutation. Endoscopic biopsies will be assessed for the presence of IM (according to the IM-score).

Study group

Oesophagogastroduodenoscopy DIAGNOSTIC_TEST

* Endoscopy will be carried out with white light and NBI with optical magnification or near focus to inspect oesophagus and GOJ. * NBI magnification will be used to assess systematically the mucosal pit pattern at the GOJ and to look for light blue crest (LBC) sign. * Targeted biopsies will be taken from either areas with LBC or irregular pit pattern on NBI, followed by random biopsies as per clinical standard. A maximum of 6 biopsies will be taken at the GOJ (maximum 4 targeted and 4 random.. During the first 2 post RFA follow up, at discretion of the endoscopists, neo-suqamous biopsies can be taken in line with local policies. * Argon plasma coagulation ablation is allowed in a single island up to 5mm or up to 3 islands \<3mm within the study endoscopy as long as this does not represent an obstacle to GOJ biopsies.

Study group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previous RFA for dysplastic BE or following EMR for BE-related neoplasia
• No definite endoscopic evidence of BE defined as at least 1cm tongue of columnar oesophagus or oesophageal BE islands larger than 5mm.
• No histological evidence of oesophageal IM including buried BE at first post RFA follow up. GOJ IM is allowed
• No evidence of suspicious lesions with dysplasia at the GOJ.

You may not qualify if:

• Evidence of BE requiring additional RFA
• Anticoagulant or antiplatelet therapy for high risk conditions, whereby discontinuation of the treatment is not recommended.
• Individuals with a diagnosis of an oro-pharynx, oesophageal or gastro-oesophageal tumour (T2 staging and above), or symptoms of dysphagia,
• Oesophageal varices, stricture or requiring dilatation of the oesophagus
• Individuals who have had a myocardial infarction or any cardiac event less than six months ago
• Patients whose primary previous ablative treatment was different from RFA, such as Photodynamic therapy (PDT), APC or Cryotherapy
• Participants who are unable to provide informed consent.
• Participants under age 18.
• Endoscopy is generally avoided in pregnant women and therefore it is unlikely that any pregnant women will be included although pregnancy would not be an absolute contraindication. Pregnancy/ pregnancy test will not be recorded as part of the trial.

Sponsors & Collaborators

• University of Cambridge: lead
• University of Nottingham: collaborator

Study Sites (1)

MRC Cancer Unit

Cambridge, CB2 0XZ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Barrett Esophagus

Interventions

Endoscopy, Digestive System

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Massimiliano Di Pietro, MD

  MRC Cancer Unit, Hutchison-MRC Research Hon. Consultant Gastroenterologist, Addenbrooke's Hospital, Cambridge.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimiliano Di Pietro, MD

CONTACT

01223763349; md460@mrc-cu.cam.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Massimiliano di Pietro, Senior Clinical Investigator Scientist, MRC Cancer Unit, Hutchison-MRC Research Hon. Consultant Gastroenterologist, Addenbrooke's Hospital, Cambridge.

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: November 7, 2019
• Study Start: September 1, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)