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Prospective Endoscopic Follow-up of Patients With Submucosal and High Risk Mucosal Esophageal Adenocarcinoma (PREFER)

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ClinicalTrials.gov Identifier: NCT03222635
Recruitment Status : Recruiting
First Posted : July 19, 2017
Last Update Posted : April 29, 2024
Sponsor:
Information provided by (Responsible Party):
Jacques J.G.H.M. Bergman, Amsterdam UMC, location VUmc

Study Description
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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 (1-5). 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 retrospective analysis from our own research group shows that this risk may be higher than previously assumed (6). In this nationwide retrospective study, we analyzed 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) and high risk mucosal (T1aN0M0) 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Upon achieving the designated sample size of 141 patients of the original PREFER-trial, the enrolment of further patients diagnosed with T1b N0M0 EAC and treated endoscopically will be continued as a registration cohort (no sample size) within the same study database.

The high-risk T1a group will also continue as a registration cohort, 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Endoscopic Management of Patients With High Risk T1a and T1b N0M0 Esophageal Adenocarcinoma: a Prospective Multicenter Registry.
Actual Study Start Date : July 25, 2017
Estimated Primary Completion Date : July 25, 2028
Estimated Study Completion Date : July 25, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy

Arms and Interventions
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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 (N0M0) will undergo endoscopic follow-up.
 Procedure: Endoscopic follow-up
Endoscopic follow-up by means of regular upper endoscopies and endoscopic ultrasounds


Outcome Measures
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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.


Eligibility Criteria
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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, by an 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.
Contacts and Locations
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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: Vincent Bos, MD +31204445500 v.bos@amsterdamumc.nl

Locations
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Sponsors and Collaborators
Amsterdam UMC
Investigators
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Principal Investigator: J. J. Bergman, MD, PhD Amsterdam UMC
Principal Investigator: R. E. Pouw, MD, PhD Amsterdam UMC
More Information
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Publications:

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Responsible Party: Jacques J.G.H.M. Bergman, Professor of Gastrointestinal Endoscopy, Amsterdam UMC, location VUmc
ClinicalTrials.gov Identifier: NCT03222635    
Other Study ID Numbers: NL6116501817
First Posted: July 19, 2017    Key Record Dates
Last Update Posted: April 29, 2024
Last Verified: April 2024
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 Jacques J.G.H.M. Bergman, Amsterdam UMC, location VUmc:
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