Clinical trial NCT03427346: Neoplastic Barrett Esophagus: Endoscopic Piecemeal vs. En Bloc Resection
Official title: Prospektiv-randomisierter Vergleich Von En-bloc- Versus Piecemeal-Resektion Von Barrett Neoplasien Des Ösophagus Neoplastic Barrett Esophagus: Endoscopic Piecemeal vs. En Bloc Resection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Barrett Esophagus
Barrett Adenocarcinoma
Esophagus Neoplasm
Keywords: Barrett Esophagus
ESD
EMR
Esophagus Neoplasm
endoscopic resection technique
ablation of esophageal mucosa
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2018-02-09
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will compare EMR versus ESD technique (both combined with subsequent ablative therapy) of mucosal resection in Barrett's esophagus with regard to efficacy and risk in a long term setting.

Detailed description: For Barrett's Esophagus neoplasia of at least LGIN up to early adenocarcinoma, the aim is to debulk or completely treat polypoid dysplastic or malignant lesions in Barrett's esophagus. The Endoscopic Mucosal Resection EMR has been established to be a less invasive, safe, and effective nonsurgical therapy. The most commonly employed modalities of EMR include snare resection with and without prior submucosal injection of fluid, and resection using a cap. Since resection of larger areas can only be done piece - by- piece this kind or resection is also called piecemeal resection or piecemeal EMR. Meanwhile, another endoscopic resection has been developed called Endoscopic Submucosal Dissection ESD.It enables complete resection of neoplasms that were impossible to resect en bloc by EMR. After circumferential cutting of the surrounding mucosa of the lesion, fluid is injected into the submucosa to elevate the lesion from the muscle layer, and subsequently the connective tissue beneath the lesion is dissected. As a basic principle on histopathological and oncological terms, the en bloc resection is to be preferred since resection integrity can be evaluated much more securely. However, complexity of this kind of resection technique as well as complication rates can be different and sometimes higher than with EMR. Current approach treating Barrett's esophagus is to eradicate both neoplastic as well as pre neoplastic or non neoplastic Barrett mucosa in order to lower the relapse risk. Current treatment standard is to combine resection of visible neoplastic areas with subsequent thermo-ablation such as RFA or APC, so this approach will also be the basis of the present study. Since RFA has the largest volume of data screened it shall be the preferred method of ablation in this study.In total, data situation ist inconsistent. Short- and Long term of EMR is excellent in centres(Pech et al, Gastroenterology 2014) whereas ESD achieved only suboptimal outcomes in tree minor western studies (Neuhaus et al. Endoscopy 2012, Höbel et al., Surg Endosc 2015, Chevaux et al. Endoscopy 2015). One randomised study published in 2016 (Terheggen et al. Gut 2016) had a higher rate of R0 resections with ESD on 40 patients but no difference in complete remissions in combination with RFA. Although, this study was not empowered sufficientliy, and also showed a higher complication rate on ESD . At present no randomised study data are availale to allow statements about long term developments, so we will set up this current randomised study. We will compare data with regard to efficacy (histological completeness and relapse rates), as well as risks, e.g. perforations and strictures or stenosis by scarring.

Eligibility criteria: Inclusion Criteria:

* patients to be treated for Barrett's esophagus by mucosal resection and following ablative therapy
* Barrett's mucosal extension up to 10 cm maximum.
* patient's ability for compliance to therapy
* signed Informed Consent

Exclusion Criteria:

* any lesion questionable to be resectable by mucosectomy, e.g. bulky lesions ≥10 mm in endoscopy und endosonography, suspected deep submucosal infiltration, ulcers, suspected or by FNA confirmed lymph node infiltration
* Barrett's esophagus \> 10 cm
* lesions that would afford resection of more than 2/3rd of esophagal circumference
* two or more single Barrett's lesions with bulky HGIN or early cancer histology, not to be resectable in one half of esophageal circumference
* planned circumferencial resections
* very serious general illness and metastatic carcinoma
* coagulation disorder or anticoagulants that make biopsies and resections impossible
* American Society of Anesthesiologists (ASA) status \> III
* pregnancy and lactation
* remainders or recurrences after therapeutic history of Barrett's espohagus

Primary outcomes:
measure: Eradication rate of neoplastic Barrett's Esophagus, initial therapy success
timeFrame: 3 months after end of therapy (resection and ablation)
measure: Eradication rate of neoplastic Barrett's Esophagus, initial therapy success
timeFrame: 9 months after end of therapy (resection and ablation)
measure: Eradication rate of neoplastic Barrett's Esophagus
timeFrame: 24 months after end of therapy (resection and ablation)
measure: Eradication rate of neoplastic Barrett's Esophagus
timeFrame: 33 months after end of therapy (resection and ablation)
Secondary outcomes:
measure: Eradication rate of complete Barrett's Esophagus, initial therapy success
timeFrame: 3 months after end of treatment (resection and ablation)
measure: Eradication rate of complete Barrett's Esophagus, initial therapy success
timeFrame: 9 months after end of treatment (resection and ablation)
measure: Eradication rate of complete Barrett's Esophagus, freedom of recurrence
timeFrame: 24 months after end of treatment (resection and ablation)
measure: Eradication rate of complete Barrett's Esophagus, freedom of recurrence
timeFrame: 33 months after end of treatment (resection and ablation)
measure: Recurrence rate of neoplastic Barrett's Esophagus, initial therapy success
timeFrame: 3 months after end of therapy (resection and ablation)
measure: Recurrence rate of neoplastic Barrett's Esophagus, initial therapy success
timeFrame: 9 months after end of therapy (resection and ablation)
measure: freedom of recurrence rate of complete Barrett's Esophagus, initial therapy success
timeFrame: 9 months after end of treatment (resection and ablation)
measure: ESD success of resection
timeFrame: 2 days
measure: EMR success of resection
timeFrame: 9 months after end of treatment (resection and ablation)
measure: Surveillance of Barrett's mucosa after incomplete resections and recurrences
timeFrame: 51 months
measure: conclusions of Tumor Board in case of re resection and outcome if postitive cancer histology
timeFrame: 51 months
measure: Determination of differences in Barrett's esophagus subtypes: size
timeFrame: 3 months
measure: Determination of differences in Barrett's esophagus subtypes: form
timeFrame: 3 months
measure: Determination of differences in Barrett's esophagus subtypes: patterns
timeFrame: 3 months
measure: Determination of differences in Barrett's esophagus subtypes: histologies
timeFrame: 3 months
measure: Intervention time
timeFrame: 18 months
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: Ph D, Director, Head of department
name: Thomas Rösch, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: BARRETT NR. The lower esophagus lined by columnar epithelium. Surgery. 1957 Jun;41(6):881-94. No abstract available.
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citation: Hobel S, Dautel P, Baumbach R, Oldhafer KJ, Stang A, Feyerabend B, Yahagi N, Schrader C, Faiss S. Single center experience of endoscopic submucosal dissection (ESD) in early Barrett's adenocarcinoma. Surg Endosc. 2015 Jun;29(6):1591-7. doi: 10.1007/s00464-014-3847-5. Epub 2014 Oct 8.
citation: Labenz J, Koop H, Tannapfel A, Kiesslich R, Holscher AH. The epidemiology, diagnosis, and treatment of Barrett's carcinoma. Dtsch Arztebl Int. 2015 Mar 27;112(13):224-33; quiz 234. doi: 10.3238/arztebl.2015.0224.
citation: Neuhaus H. Endoscopic mucosal resection and endoscopic submucosal dissection in the West--too many concerns and caveats? Endoscopy. 2010 Oct;42(10):859-61. doi: 10.1055/s-0030-1255724. Epub 2010 Sep 30. No abstract available.
citation: Pech O, May A, Manner H, Behrens A, Pohl J, Weferling M, Hartmann U, Manner N, Huijsmans J, Gossner L, Rabenstein T, Vieth M, Stolte M, Ell C. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology. 2014 Mar;146(3):652-660.e1. doi: 10.1053/j.gastro.2013.11.006. Epub 2013 Nov 20.
citation: Phoa KN, Pouw RE, Bisschops R, Pech O, Ragunath K, Weusten BL, Schumacher B, Rembacken B, Meining A, Messmann H, Schoon EJ, Gossner L, Mannath J, Seldenrijk CA, Visser M, Lerut T, Seewald S, ten Kate FJ, Ell C, Neuhaus H, Bergman JJ. Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II). Gut. 2016 Apr;65(4):555-62. doi: 10.1136/gutjnl-2015-309298. Epub 2015 Mar 2.
citation: Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med. 2014 Aug 28;371(9):836-45. doi: 10.1056/NEJMra1314704. No abstract available.