Clinical trial NCT04155242: The Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia
Official title: Prospective Study on the Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Barrett's Oesophagus
Keywords: Barrett's oesophagus
Radiofrequency ablation
Early Oesophageal Neoplasia
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: University of Nottingham
First posted: 2019-11-07
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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 .

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.

Eligibility criteria: Inclusion Criteria

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

Exclusion criteria

1. Evidence of BE requiring additional RFA
2. Anticoagulant or antiplatelet therapy for high risk conditions, whereby discontinuation of the treatment is not recommended.
3. Individuals with a diagnosis of an oro-pharynx, oesophageal or gastro-oesophageal tumour (T2 staging and above), or symptoms of dysphagia,
4. Oesophageal varices, stricture or requiring dilatation of the oesophagus
5. Individuals who have had a myocardial infarction or any cardiac event less than six months ago
6. Patients whose primary previous ablative treatment was different from RFA, such as Photodynamic therapy (PDT), APC or Cryotherapy
7. Participants who are unable to provide informed consent.
8. Participants under age 18.
9. 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.

Primary outcomes:
measure: Diagnostic accuracy of methylation panel for diffuse IM at the GOJ
timeFrame: 5 years
Secondary outcomes:
measure: Proportion of patients developing true BE recurrence
timeFrame: 5 years
measure: Biomarker score for BE recurrence
timeFrame: 5 years
measure: Accuracy of Light Blue Crest sign
timeFrame: 5 years
measure: Safety of Cytosponge
timeFrame: 5 years
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: MRC Cancer Unit
Study officials:
affiliation: MRC Cancer Unit, Hutchison-MRC Research Hon. Consultant Gastroenterologist, Addenbrooke's Hospital, Cambridge.
name: Massimiliano Di Pietro, MD
role: PRINCIPAL_INVESTIGATOR
References: