CClinicalTrials.gg
RecruitingNCT03183115Updated Mar 3, 2023

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

An interventional study of Radiofrequency ablation and Endoscopy in Esophageal Squamous Cell Neoplasm, sponsored by E-DA Hospital. Recruiting at 1 site in Taiwan. Open to participants aged 20 Years to 90 Years. Per ClinicalTrials.gov, last updated 2023-03-03.

Sponsored by E-DA Hospital · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
20 Years to 90 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Esophageal Squamous Cell Neoplasm

Keywords

  • Early esophageal squamous cell neoplasm
  • Radiofrequency ablation
  • Endoscopic submucosal dissection
  • Esophageal cancer
  • Recurrence
  • Field cancerization
03

Who can participate

Ages eligible
20 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
100 participants (estimated)

Study arms

  • Experimental
    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.

    Procedure: Radiofrequency ablation · Device: Endoscopy · Drug: Lugol's Solution (1.5%)

  • No intervention
    Control group

    No intervention; surveillance endoscopy alone

Interventions

  • ProcedureRadiofrequency 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.

  • DeviceEndoscopy

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

  • DrugLugol's Solution (1.5%)

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

05

What researchers measure

Primary outcomes

  1. Tumor recurrence

    Metachronous tumor recurrence is defined as a tumor (high-grade dysplasia or squamous cell carcinoma) recurring at a new site after more than 6 months of complete remission status.

    Time frame: From date of randomization until the date of first documented tumor recurrence, assessed up to 100 months

Secondary outcomes

  1. Major adverse events

    including perforation, dysphagia, stenosis, defined as the failure of a standard endoscope (9.8 mm in diameter) to pass through the stenosis, or others resulting in the patients intolerable and discontinued intervention.

    Time frame: From date of intervention until the date of first documented adverse events, assessed up to 12months

06

Study locations

1 of 1 sites recruiting
  • EDA Hospital
    Kaohsiung City, 82445, Taiwan
    Recruiting
07

References and documents

Publications

  • 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. PubMed 20669074 ↗
  • 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. PubMed 22423666 ↗
  • 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. PubMed 11474389 ↗
  • 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. PubMed 19340732 ↗
  • 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. PubMed 12297767 ↗
  • 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. PubMed 19474425 ↗
  • 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. PubMed 21679712 ↗
  • 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. PubMed 24668102 ↗
  • 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. PubMed 21839994 ↗
  • 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. PubMed 21455869 ↗
  • 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. PubMed 25257127 ↗
  • 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. PubMed 26656367 ↗
  • 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. PubMed 25668428 ↗

Individual participant data

Plan to share: Undecided — The initial outcome and the data of adverse events will be shared with other researchers, by mail, when they are available.

08

Registry details

Key details

Study ID
NCT03183115
Lead sponsor
E-DA Hospital
Collaborators
National Taiwan University Hospital
Responsible party
Sponsor
First posted
Jun 9, 2017
Start date
Apr 18, 2016
Primary completion
Oct 30, 2025 (estimated)
Completion
Dec 30, 2026 (estimated)
Last update
Mar 3, 2023

Study contacts

Wen-Lun Wang, Ph.D
Contact
warrengodr@gmail.com
886-7-6150011 ext. 251346
Ching-Tai Lee, M.D.
Contact
fattoo@gmail.com
886-7-6150011 ext. 251205

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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