Barrett's OesophagusPROBANNCT04155242
The Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia
A study testing Cytosponge test, Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation and Oesophagogastroduodenoscopy in people with Barrett's Oesophagus, run by University of Cambridge at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett's Oesophagus
- What is being tested?
- Cytosponge test, Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation and Oesophagogastroduodenoscopy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2020to 1 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
MRC Cancer Unit
Cambridge, CB2 0XZ
Massimiliano di Pietro, MD, 01223763349, md460@mrc-cu.cam.ac.uk
About this study
Official title: Prospective Study on the Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia
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 .
Read the detailed description
The panel of predetermined molecular biomarkers includes:
- 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
- Methylation markers- assessed by a PCR-based method (Methylight) on Cytosponge samples.
- P53 status.
- TFF3 protein expression.
- Conditions
- Barrett's Oesophagus
- Being tested
- Cytosponge test, Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation, Oesophagogastroduodenoscopy
- Keywords
- Barrett's oesophagus, Radiofrequency ablation, Early Oesophageal Neoplasia
- Medical subject headings
- Barrett Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytosponge testDiagnostic 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 mutationDiagnostic 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).
OesophagogastroduodenoscopyDiagnostic 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 | Role | What they receive |
|---|---|---|
| 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years
Secondary outcomes (4)
Proportion of patients developing true BE recurrence
Number of patients with GOJ IM with different IM score that will develop true BE recurrence during the observation period defined as oesophageal IM or dysplasia.
Measured: 5 years
Biomarker score for BE recurrence
The accuracy of a biomarker panel to predict risk of BE recurrence. The following biomarkers will be assessed:
- P53 status by immunohistochemistry
- TFF3 expression by immunohistochemistry
- IM-SCORE (defined in the Study Description section)
- methylation markers (defined in the Outcome 1 Description section).
Measured: 5 years
Accuracy of Light Blue Crest sign
Diagnostic accuracy of a Light Blue Crest (LBC) sign in NBI for the diagnosis of GOJ IM. During each performed endoscopy, NBI magnification will be used to assess systematically the mucosal pit pattern at the GOJ and to look for the LBC sign. In order to assess the accuracy of LBC, targeted biopsies will be taken from all the areas with LBC.
Measured: 5 years
Safety of Cytosponge
Number of participants with Cytosponge procedure-related serious adverse events defined as an event that:
Results in death Is life-threatening Requires hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability or incapacity Consists of a congenital anomaly or birth defect Is otherwise considered medically significant by the investigator (eg. a further procedure is required for the patient).
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start1 Sep 2020
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Barrett's OesophagusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 147 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nottingham
- Responsible party
- Principal investigator, Massimiliano di Pietro, MD, University of Cambridge
- Investigators
- Massimiliano Di Pietro, MD, Principal investigator, MRC Cancer Unit, Hutchison-MRC Research Hon. Consultant Gastroenterologist, Addenbrooke's Hospital, Cambridge.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04155242
- Sponsor's protocol ID
- ISRCTN12730505
- Acronym
- PROBAN
- Status last verified
- May 2024
- First submitted
- 25 Oct 2019
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study on the Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia
- ClinicalTrials.gov ID
- NCT04155242
- Acronym / sponsor ID
- PROBAN / ISRCTN12730505
- Conditions
- Barrett's Oesophagus
- Keywords
- Barrett's oesophagus, Radiofrequency ablation, Early Oesophageal Neoplasia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 147 participants (estimated)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- University of Nottingham
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 7 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- Methylation markers- assessed by a PCR-based method (Methylight) on Cytosponge samples.
- P53 status.
- TFF3 protein expression.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study group | Experimental | Diagnostic Test: Cytosponge test, Diagnostic Test: Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation, Diagnostic Test: OesophagogastroduodenoscopyAs 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytosponge testThe 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 | Study group |
| Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutationMolecular 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 | Study group |
| 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. | Diagnostic test | Study group |
Primary outcome
Diagnostic accuracy of methylation panel for diffuse IM at the GOJ
Time frame: 5 years
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.
4 secondary outcomes
Proportion of patients developing true BE recurrence
Time frame: 5 years
Biomarker score for BE recurrence
Time frame: 5 years
Accuracy of Light Blue Crest sign
Time frame: 5 years
Safety of Cytosponge
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Individual participant dataSharing planned: No
Related trials for Barrett's Oesophagus
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 4
Efficacy of Potassium-Competitive Acid Blockers in Barrett's Esophagus (PCAB BE Study)
Barrett Esophagus
RecruitingObservational study
"Less-is-more in Barrett-surveillance" Care Evaluation of Barrett's Patients With Low-Risk in Whom Endoscopic Surveillance is Stopped. The BLISS Project.
Barrett Esophagus, Barrett Esophagus Adenocarcinoma
Not yet recruitingObservational study
Lucid BE Biomarkers Study
Barrett's Esophagus, Barrett's Esophagus With Dysplasia
RecruitingObservational study
Impact of RFA on Esophageal Distensibility and Mucosal Impedance
Dysplastic Barrett's Esophagus, Radiofrequency Ablation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Massimiliano Di Pietro, MD principal investigator
MRC Cancer Unit, Hutchison-MRC Research Hon. Consultant Gastroenterologist, Addenbrooke's Hospital, Cambridge.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cytosponge test, Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation and Oesophagogastroduodenoscopy in people with Barrett's Oesophagus, run by University of Cambridge at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Massimiliano Di Pietro, MD (01223763349, md460@mrc-cu.cam.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of methylation panel for diffuse IM at the GOJ (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.