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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03222635
Recruitment Status : Recruiting
First Posted : July 19, 2017
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
prof. dr. J.J.G.H.M. Bergman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Submucosal Esophageal Adenocarcinoma Barrett Esophagus High-risk Mucosal Esophageal Adenocarcinoma Procedure: Endoscopic follow-up Not Applicable

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 However, a recent (unpublished) retrospective analysis from our own research group shows that this risk may be higher than previously assumed.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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 141 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Sample size T1b patients = n=141. No sample size will be calculated for the HR T1a patient group, since there is no available data yet to calculate a reliable sample size with. The high risk T1a patient group will be analysed separately from the T1b patient group and included high risk T1a patients will therefore not be counted as true inclusions for the PREFER study's calculated sample size of 141 patients.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Endoscopic Management of Patients With T1bN0M0 Esophageal Adenocarcinoma: a Prospective Multicenter Registry.
Actual Study Start Date : July 25, 2017
Estimated Primary Completion Date : July 25, 2025
Estimated Study Completion Date : July 25, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy

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




Primary Outcome Measures :
  1. 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.

  2. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03222635


Contacts
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Contact: Esther Nieuwenhuis, MD +31645916097 e.a.nieuwenhuis@amsterdamumc.nl
Contact: W. D. Rosmolen, Master +31205663252 w.d.rosmolen@amsterdamumc.nl

Locations
Show Show 18 study locations
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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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)
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Responsible Party: prof. dr. J.J.G.H.M. Bergman, Professor of Gastrointestinal Endoscopy, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03222635    
Other Study ID Numbers: NL6116501817
First Posted: July 19, 2017    Key Record Dates
Last Update Posted: January 14, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by prof. dr. J.J.G.H.M. Bergman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Barrett's esophagus
Submucosal esophageal adenocarcinoma
Endoscopic treatment
Endoscopic follow-up
High-risk mucosal esophageal adenocarcinoma
Additional relevant MeSH terms:
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Adenocarcinoma
Barrett Esophagus
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Precancerous Conditions
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms