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

NCT ID: NCT03222635

Last Updated: 2024-07-24

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

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-25

Study Completion Date

2028-07-25

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Submucosal Esophageal Adenocarcinoma Barrett Esophagus High-risk Mucosal Esophageal Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Endoscopic follow-up

Intervention Type PROCEDURE

Endoscopic follow-up by means of regular upper endoscopies and endoscopic ultrasounds

Interventions

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Endoscopic follow-up

Endoscopic follow-up by means of regular upper endoscopies and endoscopic ultrasounds

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amsterdam UMC

OTHER

Sponsor Role lead

Responsible Party

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Jacques J.G.H.M. Bergman

Professor of Gastrointestinal Endoscopy

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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J. J. Bergman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

R. E. Pouw, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

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Westmead hospital

Sydney, , Australia

Site Status RECRUITING

CUB Hôpital Erasme

Brussels, , Belgium

Site Status RECRUITING

AZ Maria Middelares Ghent

Ghent, , Belgium

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

AZ Delta Roeselare

Roeselare, , Belgium

Site Status RECRUITING

Universitätsklinikum Augsburg

Augsburg, , Germany

Site Status RECRUITING

EVK Duesseldorf

Düsseldorf, , Germany

Site Status RECRUITING

MRI TUM

Münich, , Germany

Site Status ACTIVE_NOT_RECRUITING

Barmherzige Brüder Regensburg

Regensburg, , Germany

Site Status RECRUITING

Amsterdam UMC

Amsterdam, , Netherlands

Site Status RECRUITING

Catharina Hospital

Eindhoven, , Netherlands

Site Status RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

St. Antonius Hospital

Nieuwegein, , Netherlands

Site Status RECRUITING

Radboudumc

Nijmegen, , Netherlands

Site Status RECRUITING

Erasmus MC - University Medical Center

Rotterdam, , Netherlands

Site Status RECRUITING

Haga Medical Center

The Hague, , Netherlands

Site Status RECRUITING

Isala Clinics

Zwolle, , Netherlands

Site Status RECRUITING

Hirslanden private hospital group

Zurich, , Switzerland

Site Status RECRUITING

University College London Hospital

London, , United Kingdom

Site Status RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status RECRUITING

Countries

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Australia Belgium Germany Netherlands Switzerland United Kingdom

Central Contacts

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Vincent Bos, MD

Role: CONTACT

+31204445500

Facility Contacts

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M. Bourke, MD, PhD

Role: primary

Arnaud Lemmers, MD, PhD

Role: primary

P. Dewint, MD, PhD

Role: primary

R. Bisschops, MD, PhD

Role: primary

D. De Wulf, MD, PhD

Role: primary

H. Messmann

Role: primary

Horst Neuhaus

Role: primary

Oliver Pech

Role: primary

V. Bos, MD

Role: primary

E. J. Schoon, MD, PhD

Role: primary

W. B. Nagengast, MD, PhD

Role: primary

B. L. Weusten, MD, PhD

Role: primary

G. J. Bulte, MD, PhD

Role: primary

A. D. Koch, MD, PhD

Role: primary

M. Houben, MD, PhD

Role: primary

B. E. Schenk, MD, PhD

Role: primary

S. Seewald

Role: primary

R. Haidry, MD, PhD

Role: primary

J. Ortiz, MD, PhD

Role: primary

References

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Alvarez Herrero L, Pouw RE, van Vilsteren FG, ten Kate FJ, Visser M, van Berge Henegouwen MI, Weusten BL, Bergman JJ. Risk of lymph node metastasis associated with deeper invasion by early adenocarcinoma of the esophagus and cardia: study based on endoscopic resection specimens. Endoscopy. 2010 Dec;42(12):1030-6. doi: 10.1055/s-0030-1255858. Epub 2010 Oct 19.

Reference Type BACKGROUND
PMID: 20960392 (View on PubMed)

Scholvinck D, Kunzli H, Meijer S, Seldenrijk K, van Berge Henegouwen M, Bergman J, Weusten B. Management of patients with T1b esophageal adenocarcinoma: a retrospective cohort study on patient management and risk of metastatic disease. Surg Endosc. 2016 Sep;30(9):4102-13. doi: 10.1007/s00464-016-5071-y. Epub 2016 Jun 29.

Reference Type BACKGROUND
PMID: 27357927 (View on PubMed)

Manner H, May A, Pech O, Gossner L, Rabenstein T, Gunter E, Vieth M, Stolte M, Ell C. Early Barrett's carcinoma with "low-risk" submucosal invasion: long-term results of endoscopic resection with a curative intent. Am J Gastroenterol. 2008 Oct;103(10):2589-97. doi: 10.1111/j.1572-0241.2008.02083.x. Epub 2008 Sep 10.

Reference Type BACKGROUND
PMID: 18785950 (View on PubMed)

Manner H, Pech O, Heldmann Y, May A, Pohl J, Behrens A, Gossner L, Stolte M, Vieth M, Ell C. Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion. Clin Gastroenterol Hepatol. 2013 Jun;11(6):630-5; quiz e45. doi: 10.1016/j.cgh.2012.12.040. Epub 2013 Jan 26.

Reference Type BACKGROUND
PMID: 23357492 (View on PubMed)

Manner H, Pech O, Heldmann Y, May A, Pauthner M, Lorenz D, Fisseler-Eckhoff A, Stolte M, Vieth M, Ell C. The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns. Surg Endosc. 2015 Jul;29(7):1888-96. doi: 10.1007/s00464-014-3881-3. Epub 2014 Oct 8.

Reference Type BACKGROUND
PMID: 25294553 (View on PubMed)

Nieuwenhuis EA, van Munster SN, Meijer SL, Brosens LAA, Jansen M, Weusten BLAM, Alvarez Herrero L, Alkhalaf A, Schenk E, Schoon EJ, Curvers WL, Koch AD, van de Ven SEM, Verheij EPD, Nagengast WB, Westerhof J, Houben MHMG, Tang T, Bergman JJGHM, Pouw RE; Dutch Barrett Expert Centers. Analysis of metastases rates during follow-up after endoscopic resection of early "high-risk" esophageal adenocarcinoma. Gastrointest Endosc. 2022 Aug;96(2):237-247.e3. doi: 10.1016/j.gie.2022.03.005. Epub 2022 Mar 12.

Reference Type BACKGROUND
PMID: 35288149 (View on PubMed)

Other Identifiers

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NL6116501817

Identifier Type: -

Identifier Source: org_study_id

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