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

NCT ID: NCT04155242

Last Updated: 2024-05-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

147 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-01

Study Completion Date

2024-12-01

Brief Summary

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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

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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

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Barrett's Oesophagus

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Study group

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.

Group Type EXPERIMENTAL

Cytosponge test

Intervention Type 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.

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

Intervention Type 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).

Oesophagogastroduodenoscopy

Intervention Type 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.

Interventions

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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.

Intervention Type 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).

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Nottingham

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role lead

Responsible Party

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Massimiliano di Pietro, MD

Dr Massimiliano di Pietro, Senior Clinical Investigator Scientist, MRC Cancer Unit, Hutchison-MRC Research Hon. Consultant Gastroenterologist, Addenbrooke's Hospital, Cambridge.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Massimiliano Di Pietro, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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MRC Cancer Unit

Cambridge, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Massimiliano Di Pietro, MD

Role: CONTACT

01223763349

Facility Contacts

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Massimiliano di Pietro, MD

Role: primary

01223763349

Other Identifiers

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ISRCTN12730505

Identifier Type: -

Identifier Source: org_study_id

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