RFA to Prevent Metachronous Squamous Neoplasia Recurrence After Complete Endoscopic Submucosal Dissection

NCT ID: NCT03183115

Last Updated: 2023-03-03

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

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-18

Study Completion Date

2026-12-30

Brief Summary

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Esophageal cancer is a highly lethal disease, and its incidence is still increasing in the world. Recent advances in image-enhanced techniques such as Lugol chromoendoscopy and narrow band imaging, the number of patients with early esophageal squamous cell neoplasias (ESCNs) detected has markedly increased. Endoscopic submucosal dissection (ESD) enables en bloc resection of the neoplasia, and the resected specimen allows for a pathological assessment to evaluate the curability. However, the patients who received complete ESD for early ESCNs frequently developed metachronous recurrence. The cumulative metachronous recurrence rate at 5 years was 50%, and the mean annual incidence of newly diagnosed metachronous tumors was 10%. Among them, those with "speckled" lugol staining pattern over the esophageal background mucosa have the highest risk and should be seen as a precancerous lesion of ESCCs. This issue is gaining attention in the era of endoscopic treatment, but currently there was no appropriate strategy to prevent the tumor recurrence in these high-risk subjects.

Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality, and recent studies have shown its efficacy and safety for eradicating for flat type early ESCNs. To search a best strategy for the prevention of ESCNs, the investigators thus propose a hypothesis that the preemptive RFA for esophageal "speckled" lugol background mucosa may prevent the metachronous neoplastic recurrence after complete endoscopic resection.

Detailed Description

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Conditions

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Esophageal Squamous Cell Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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RFA group

Balloon type RFA (12J/cm2, 1 application) will be applied for the entire speckled esophageal mucosa at the 3 months after complete ESD.

Oral prednisolone 30mg/day will be prescribed at day 3 after RFA procedure and continue for 28 days to prevent the post-RFA stenosis.

Group Type EXPERIMENTAL

Radiofrequency ablation

Intervention Type PROCEDURE

HALO360 System (Covidien GI Solutions, Sunnyvale, California, USA), which has been approved by the US Food and Drug Administration (FDA) and is approved for use in Europe (CE mark) and Taiwan (Ministry of Health and Welfare). Because the HALO 360 balloon catheter has been phased out since 2019, a new Barrx™ 360 Express catheter was used thereafter.

Endoscopy

Intervention Type DEVICE

The participants will receive meticulous endoscopic examination with Lugol chromoendoscopy and Narrow-band imaging

Lugol's Solution (1.5%)

Intervention Type DRUG

Before the RFA intervention, the participants will received Lugol staining over the esophagus

Control group

No intervention; surveillance endoscopy alone

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Radiofrequency ablation

HALO360 System (Covidien GI Solutions, Sunnyvale, California, USA), which has been approved by the US Food and Drug Administration (FDA) and is approved for use in Europe (CE mark) and Taiwan (Ministry of Health and Welfare). Because the HALO 360 balloon catheter has been phased out since 2019, a new Barrx™ 360 Express catheter was used thereafter.

Intervention Type PROCEDURE

Endoscopy

The participants will receive meticulous endoscopic examination with Lugol chromoendoscopy and Narrow-band imaging

Intervention Type DEVICE

Lugol's Solution (1.5%)

Before the RFA intervention, the participants will received Lugol staining over the esophagus

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Adults with early stage ESCNs (squamous high grade dysplasia, carcinoma in situ, or T1N0M0 SCC) who were treated by endoscopic submucosal dissection.
* Lugol staining showed "speckled" (\>10 small lugol-unstained lesions) pattern of background mucosa.

Exclusion Criteria

* Having a history of incomplete endoscopic treatment, or complications during/after treatment (perforation, stricture).
* Having history of systemic chemotherapy or radiation therapy for esophagus or post esophagectomy.
* Life expectancy \<2 yr.
* Decompensated cirrhosis (Child score B, C).
* Having large esophageal varices.
* Poor performance status (ECOG\>2).
Minimum Eligible Age

20 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role collaborator

E-DA Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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EDA Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Wen-Lun Wang, Ph.D

Role: CONTACT

886-7-6150011 ext. 251346

Ching-Tai Lee, M.D.

Role: CONTACT

886-7-6150011 ext. 251205

Facility Contacts

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Wen-Lun Wang, Ph.D

Role: primary

886-7-6150011 ext. 251346

References

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Lee CT, Chang CY, Lee YC, Tai CM, Wang WL, Tseng PH, Hwang JC, Hwang TZ, Wang CC, Lin JT. Narrow-band imaging with magnifying endoscopy for the screening of esophageal cancer in patients with primary head and neck cancers. Endoscopy. 2010 Aug;42(8):613-9. doi: 10.1055/s-0030-1255514. Epub 2010 Jul 28.

Reference Type RESULT
PMID: 20669074 (View on PubMed)

Lee CT, Chang CY, Tai CM, Wang WL, Tseng CH, Hwang JC, Lin JT. Endoscopic submucosal dissection for early esophageal neoplasia: a single center experience in South Taiwan. J Formos Med Assoc. 2012 Mar;111(3):132-9. doi: 10.1016/j.jfma.2010.12.002. Epub 2012 Feb 8.

Reference Type RESULT
PMID: 22423666 (View on PubMed)

Shimizu Y, Tukagoshi H, Fujita M, Hosokawa M, Kato M, Asaka M. Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection. Gastrointest Endosc. 2001 Aug;54(2):190-4. doi: 10.1067/mge.2001.116877.

Reference Type RESULT
PMID: 11474389 (View on PubMed)

Urabe Y, Hiyama T, Tanaka S, Oka S, Yoshihara M, Arihiro K, Chayama K. Metachronous multiple esophageal squamous cell carcinomas and Lugol-voiding lesions after endoscopic mucosal resection. Endoscopy. 2009 Apr;41(4):304-9. doi: 10.1055/s-0029-1214477. Epub 2009 Apr 1.

Reference Type RESULT
PMID: 19340732 (View on PubMed)

Muto M, Hironaka S, Nakane M, Boku N, Ohtsu A, Yoshida S. Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer. Gastrointest Endosc. 2002 Oct;56(4):517-21. doi: 10.1067/mge.2002.128104.

Reference Type RESULT
PMID: 12297767 (View on PubMed)

Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009 May 28;360(22):2277-88. doi: 10.1056/NEJMoa0808145.

Reference Type RESULT
PMID: 19474425 (View on PubMed)

Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, Sharma VK, Eisen GM, Fennerty MB, Hunter JG, Bronner MP, Goldblum JR, Bennett AE, Mashimo H, Rothstein RI, Gordon SR, Edmundowicz SA, Madanick RD, Peery AF, Muthusamy VR, Chang KJ, Kimmey MB, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Dumot JA, Falk GW, Galanko JA, Jobe BA, Hawes RH, Hoffman BJ, Sharma P, Chak A, Lightdale CJ. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology. 2011 Aug;141(2):460-8. doi: 10.1053/j.gastro.2011.04.061. Epub 2011 May 6.

Reference Type RESULT
PMID: 21679712 (View on PubMed)

Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, Fullarton G, Di Pietro M, Ravi N, Visser M, Offerhaus GJ, Seldenrijk CA, Meijer SL, ten Kate FJ, Tijssen JG, Bergman JJ. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014 Mar 26;311(12):1209-17. doi: 10.1001/jama.2014.2511.

Reference Type RESULT
PMID: 24668102 (View on PubMed)

Bergman JJ, Zhang YM, He S, Weusten B, Xue L, Fleischer DE, Lu N, Dawsey SM, Wang GQ. Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus. Gastrointest Endosc. 2011 Dec;74(6):1181-90. doi: 10.1016/j.gie.2011.05.024. Epub 2011 Aug 15.

Reference Type RESULT
PMID: 21839994 (View on PubMed)

van Vilsteren FG, Alvarez Herrero L, Pouw RE, ten Kate FJ, Visser M, Seldenrijk CA, van Berge Henegouwen MI, Weusten BL, Bergman JJ. Radiofrequency ablation for the endoscopic eradication of esophageal squamous high grade intraepithelial neoplasia and mucosal squamous cell carcinoma. Endoscopy. 2011 Apr;43(4):282-90. doi: 10.1055/s-0030-1256309. Epub 2011 Mar 31.

Reference Type RESULT
PMID: 21455869 (View on PubMed)

Wang WL, Chang IW, Chang CY, Lin JT, Mo LR, Wang HP, Lee CT. Circumferential balloon-based radiofrequency ablation for ultralong and extensive flat esophageal squamous neoplasia. Gastrointest Endosc. 2014 Dec;80(6):1185-9. doi: 10.1016/j.gie.2014.07.025. Epub 2014 Sep 23. No abstract available.

Reference Type RESULT
PMID: 25257127 (View on PubMed)

Wang WL, Chang IW, Chen CC, Chang CY, Mo LR, Lin JT, Wang HP, Lee CT. Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia. Medicine (Baltimore). 2015 Dec;94(49):e2240. doi: 10.1097/MD.0000000000002240.

Reference Type RESULT
PMID: 26656367 (View on PubMed)

He S, Bergman J, Zhang Y, Weusten B, Xue L, Qin X, Dou L, Liu Y, Fleischer D, Lu N, Dawsey SM, Wang GQ. Endoscopic radiofrequency ablation for early esophageal squamous cell neoplasia: report of safety and effectiveness from a large prospective trial. Endoscopy. 2015 May;47(5):398-408. doi: 10.1055/s-0034-1391285. Epub 2015 Feb 10.

Reference Type RESULT
PMID: 25668428 (View on PubMed)

Wang WL, Tsai YN, Hsu MH, Lin JT, Wang HP, Lee CT. Endoscopic background mucosal resurfacing to prevent metachronous recurrence of superficial esophageal squamous cell cancer after curative endoscopic submucosal dissection: randomized pilot study with 5-year follow-up (with video). Gastrointest Endosc. 2025 Jun;101(6):1145-1154. doi: 10.1016/j.gie.2024.11.003. Epub 2024 Nov 8.

Reference Type DERIVED
PMID: 39521094 (View on PubMed)

Other Identifiers

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MOST105-2314-B-650-005

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ED102807

Identifier Type: -

Identifier Source: org_study_id

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