NCT04155242

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

Prospective Study on the Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 147 (estimated)
• Sponsor: University of Cambridge · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 .

Detailed description

The panel of predetermined molecular biomarkers includes: 1. IM-SCORE - a score quantifying the extent of intestinal metaplasia at GOJ, which uses a 4-tier system based on the number of glands and the number of biopsies with features of IM. The score has been developed in a pilot study (manuscript under submission) and will be validated in this study 2. Methylation markers- assessed by a PCR-based method (Methylight) on Cytosponge samples. 3. P53 status. 4. TFF3 protein expression.

Conditions

• Barrett's Oesophagus

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Cytosponge 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.
DIAGNOSTIC_TEST	Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation	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).
DIAGNOSTIC_TEST	Oesophagogastroduodenoscopy	* 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.

Timeline

• Start date: 2020-09-01
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2019-11-07
• Last updated: 2024-05-08

Locations

1 site across 1 country: United Kingdom