Prospective Endoscopic Follow-up of Patients With Submucosal Esophageal Adenocarcinoma (The PREFER Trial)

January 12, 2021 updated by: prof. dr. J.J.G.H.M. Bergman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Endoscopic Management of Patients With T1bN0M0 Esophageal Adenocarcinoma: a Prospective Multicenter Registry.

Aim of this prospective multicenter study is to evaluate the safety of an endoscopic follow-up strategy in patients treated with endoscopic resection (ER) for submucosal or high-risk mucosal esophageal adenocarcinoma (T1bN0M0 or HR T1aN0M0 EAC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Traditionally, the risk of lymph node metastasis associated with submucosal EAC was considered too high to offer patients endoscopic follow-up. Only in elderly patients with comorbidity, more often an endoscopic protocol is selected. However, the risk of lymph node metastasis associated with submucosal EAC is mainly based on surgical series. Recently a number of studies, which included patients treated endoscopically, were published indicating that the risk of lymph node metastasis may be much lower than generally assumed.Therefore, a less invasive and organ preserving approach may not only be an option in the frail and elderly, but for all patients with submucosal EAC's.

Yet, no data exists on the risk of lymph node metastasis in high risk T1a EAC. The risk is assumed to be lower than for EACs invading into the submucosal layer. However, a recent (unpublished) retrospective analysis from our own research group shows that this risk may be higher than previously assumed. In this nationwide retrospective study, we analysed lymph node metastasis rates and EAC related mortality rates concerning patients with high risk T1a, low risk T1b or high risk T1b EAC who received endoscopic treatment. The study was performed in 9 Barrett Expert Centers in the Netherlands (2008-2019). 120 patients were included in the analysis, and results showed the highest lymph node metastasis risk in the high risk T1a patient group Aim of this multicenter study is to prospectively evaluate the safety of endoscopic follow-up in patients treated by endoscopic resection for submucosal (T1bN0M0) EAC.

High-resolution upper endoscopy with white-light endoscopy and narrow-band imaging supplemented with an EUS are performed every three months during the first two years after ER. After 1 year, a CT-thorax/abdomen will be performed to check for distant metastasis. During the third and fourth year of follow-up, EUS and upper endoscopy are performed every six months. From the fifth year on, EUS and upper endoscopy are performed annually.

Study Type

Interventional

Enrollment (Anticipated)

141

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Sydney, Australia
        • Recruiting
        • Westmead Hospital
        • Contact:
          • M. Bourke, MD, PhD
  • Belgium
      • Leuven, Belgium
        • Recruiting
        • Uz Gasthuisberg
        • Contact:
          • R. Bisschops, MD, PhD
        • Principal Investigator:
          • R. Bisschops, MD, PhD
  • France
      • Nantes, France
        • Recruiting
        • CHU Nantes
        • Contact:
          • Emmanuel Coron
  • Germany
      • Augsburg, Germany
      • Duesseldorf, Germany
        • Recruiting
        • EVK Duesseldorf
        • Contact:
          • Horst Neuhaus
      • Münich, Germany
        • Recruiting
        • MRI TUM
        • Contact:
          • Christoph Schlag
      • Regensburg, Germany
        • Recruiting
        • Barmherzige Brüder Regensburg
        • Contact:
          • Oliver Pech
  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Academic Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • J. J. Bergman, MD, PhD
        • Principal Investigator:
          • R. E. Pouw, MD, PhD
      • Amsterdam, Netherlands
      • Eindhoven, Netherlands
        • Recruiting
        • Catharina hospital
        • Contact:
          • E. J. Schoon, MD, PhD
        • Principal Investigator:
          • E. J. Schoon, MD, PhD
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen
        • Contact:
          • W. B. Nagengast, MD, PhD
        • Principal Investigator:
          • W. B. Nagengast, MD, PhD
      • Nieuwegein, Netherlands
        • Recruiting
        • St. Antonius Hospital
        • Contact:
          • B. L. Weusten, MD, PhD
        • Principal Investigator:
          • B. L. Weusten, MD, PhD
      • Nijmegen, Netherlands
        • Recruiting
        • Radboudumc
        • Contact:
          • P. Siersema, MD, PhD
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus MC - University Medical Center
        • Contact:
          • A. D. Koch, MD, PhD
        • Principal Investigator:
          • A. D. Koch, MD, PhD
      • The Hague, Netherlands
        • Recruiting
        • Haga Medical Center
        • Contact:
          • M. Houben, MD, PhD
        • Principal Investigator:
          • M. Houben, MD, PhD
      • Zwolle, Netherlands
        • Recruiting
        • Isala Clinics
        • Contact:
          • B. E. Schenk, MD, PhD
        • Principal Investigator:
          • B. E. Schenk, MD, PhD
  • Switzerland
      • Zürich, Switzerland
        • Recruiting
        • Hirslanden private hospital group
        • Contact:
          • S. Seewald
  • United Kingdom
      • London, United Kingdom
        • Not yet recruiting
        • University College London Hospital
        • Contact:
          • R. Haidry, MD, PhD
        • Principal Investigator:
          • R. Haidry, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with submucosal or high-risk mucosal EAC diagnosed in an ER specimen, revised by a panel of expert gastrointestinal (GI) pathologists.
  • Signed informed consent.

Exclusion Criteria:

  • Prior history of high-risk mucosal or ≥T1sm.
  • Synchronous esophageal squamous cell carcinoma.
  • Suspicion on lymph node metastasis or distant metastasis on EUS, ultrasound of the neck or CT-thorax-abdomen performed six weeks after ER during baseline measurement.
  • Tumor-positive deep resection margin (R1) in ER specimen.
  • Patients unable to give signed informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Endoscopic follow-up
Patients treated with endoscopic resection (ER) for a submucosal or high-risk mucosal esophageal adenocarcinoma without lymphnode- or distant metastases (T1bN0M0 EAC) will undergo endoscopic follow-up.
Procedure: Endoscopic follow-up
Endoscopic follow-up by means of regular upper endoscopies and endoscopic ultrasounds

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year disease-specific mortality/survival (descriptive statistics in SPSS, percentages, survival analysis)
Time Frame: 5 years
Disease specific mortality is decribed as mortality directly linked to the esophageal adenocarcinoma (i.e., metastasized EAC, metastasized disease with a simultaneously primary cancer present and it cannot be ruled out (based on histology) that the metastases are related to the other primary cancer, death due to complications of the endoscopic procedure, death due to complications after surgery or CRT, no clear cause of death in patients who have metastases or untreated local recurrence). If patients are diagnosed with distant metastases, and subsequently die of a non-tumor related cause, patients will still be documented as tumor-related death. Will be measured in number of patients and percentages. Survival analysis using Kaplan Meier will be performed.
5 years
Overall survival (descriptive statistics in SPSS, percentages, survival analysis)
Time Frame: 5 years
Overall survival of study population (tumor-related + non-tumor-related deaths). Measured in numbers and percentages, survival analysis (KM).
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lymph node metastasis, confirmed by cytology and/or histology (descriptive statistics in SPSS, number of patients (%))
Time Frame: 5 years
Confirmed by cytology and/or histology by performing FNA during EUS or biopsies.
5 years
Local recurrence eligible for endoscopic therapy (descriptive statistics in SPSS, number of patients (%))
Time Frame: 5 years
In case a local recurrence is found during FU endoscopy, histopathology have to show if it is recurrent cancer.
5 years
Local recurrence requiring surgical therapy (descriptive statistics in SPSS, number of patients (%))
Time Frame: 5 years
In case a local cancer recurrence is not amendable for endoscopic re-treatment, for example due to extensive disease or fibrosis, a patient will be referred for surgery if possible.
5 years
Distant metastasis, histologically proven (descriptive statistics in SPSS, number of patients (%))
Time Frame: 5 years
Primary tumor of distant metastasis should be histopathologically evalueted by taking biopsies.
5 years
Quality of life during follow-up endoscopies (questionnaires)
Time Frame: 5 years
Quality of life is assessed by using questionnaires on set time points during the whole study.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

  • Principal Investigator: J. J. Bergman, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • Principal Investigator: R. E. Pouw, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2017

Primary Completion (Anticipated)

July 25, 2025

Study Completion (Anticipated)

July 25, 2025

Study Registration Dates

First Submitted

July 17, 2017

First Submitted That Met QC Criteria

July 18, 2017

First Posted (Actual)

July 19, 2017

Study Record Updates

Last Update Posted (Actual)

January 14, 2021

Last Update Submitted That Met QC Criteria

January 12, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL6116501817

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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