Validation of a Molecular Test for Risk-stratification of Patients With High-risk Intestinal Metaplasia (GCEP2 Study)

NCT05782465 | Active Not Recruiting

• 1 other identifier: 2019/00629
• Study Type: observational
• Target: 500
• Locations: 6 countries
• Sites: 8

Brief Summary

This study is carried out to find out if a customized molecular test can identify a subgroup of patients with very-high-risk of developing stomach cancer within patients with intestinal metaplasia (IM). The investigators hypothesise that the incidence of dysplasia and GC cases in the molecular-test-positive group will be significantly higher than that in the molecular-test-negative group. Such a test has the potential to guide clinicians to better manage patients with IM by allowing endoscopic surveillance to be focused on individuals at very-high-risk of developing stomach cancer, at the same time avoiding or reducing endoscopies for those at lower risk.

Conditions

Stomach Neoplasm

Keywords

Gastric Cancer; Stomach Neoplasm; Intestinal Metaplasia

Outcome Measures

Primary Outcomes (1)

• Gastric Cancer

  Number of patients who develop gastric cancer, including high grade dysplasia, carcinoma in-situ and adenocarcinoma

  10 years

Study Arms (1)

Participants with IM of OLGIM Stage 2 to 4

Participants with Intestinal Metaplasia of Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) that is evaluated to be Stage 2 to 4.

Procedure: Blood Collection, processing and analyses; Procedure: Gastroscopy and biopsies collection; Diagnostic Test: Urea Breath Test

Interventions

Blood Collection, processing and analyses PROCEDURE

20ml of blood will be drawn from study participant at the baseline visit for molecular analyses.

Participants with IM of OLGIM Stage 2 to 4

Gastroscopy and biopsies collection PROCEDURE

Study participant will undergo gastroscopy with collection of gastric mucosal biopsies at the baseline visit to ascertain OLGIM status and for molecular analyses. Study participant will undergo surveillance gastroscopy for gastric cancer at years 2 and 4 to assess whether they have reached endpoint.

Participants with IM of OLGIM Stage 2 to 4

Urea Breath Test DIAGNOSTIC_TEST

Study participant will fast for 6 hours or overnight before undergoing the Urea Breath Test (UBT) to test for current H. pylori infection. Breath collection will be performed before ingestion of 13C urea, and at specified time intervals after ingestion.

Participants with IM of OLGIM Stage 2 to 4

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants who have been referred to the participating study sites for gastroscopy for clinical indications, and were detected to have IM of OLGIM Stage 2 to 4 at baseline.

You may qualify if:

• The subject is above 50 years old or turns 50 years old in the year of recruitment
• The subject is below 76 years old in the year of recruitment
• The subject is willing and able to provide signed and dated patient informed consent form indicating that they has been informed of all pertinent aspects of the study

You may not qualify if:

• The subject who has bleeding disorders, such as haemophilia, in whom biopsies are contraindicated.
• The subject with a personal history of high-grade dysplasia or GC.
• The subject with liver cirrhosis.
• The subject with previous total or partial gastrectomy.
• The subject with severe co-morbid illness, such as end-stage renal failure (ESRF), congestive cardiac failure (CCF), severe osteoarthritis (OA), and rheumatoid arthritis (RA) requiring long-term non-steroidal anti-inflammatory drug (NSAID) therapy.
• The subject with other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and in the judgement of the investigator would make the subject unsuitable for entry into the study.
• The subject on regular anti-coagulant prophylaxis such as warfarin must be able to undergo a 5-day washout period before each gastroscopy. The subject on aspirin, ticlopidine and clopidogrel must be able to undergo a one-week washout period before each gastroscopy. The subject's physician or study co-investigator will exercise their clinical judgement to ensure subject's safety.
• The subject is unwilling or unable to provide signed informed consent.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Tan Tock Seng Hospital: collaborator
• Singapore General Hospital: collaborator
• Yonsei University: collaborator
• Stanford University: collaborator
• Chinese University of Hong Kong: collaborator
• Nihon University: collaborator
• National Taiwan University Hospital: collaborator

Study Sites (8)

Stanford University

Stanford, California, 94305, United States

Location

The Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

Nihon University School of Medicine

Tokyo, Japan

Location

Singapore General Hospital

Singapore, Singapore, 169608, Singapore

Location

Tan Tock Seng Hospital, Singapore

Singapore, Singapore, 308433, Singapore

Location

National University Hospital

Singapore, 119074, Singapore

Location

Yonsei University, Republic of Korea

Seoul, South Korea

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (10)

• de Vries AC, Kuipers EJ. Epidemiology of premalignant gastric lesions: implications for the development of screening and surveillance strategies. Helicobacter. 2007 Nov;12 Suppl 2:22-31. doi: 10.1111/j.1523-5378.2007.00562.x.

  PMID: 17991173 BACKGROUND

• Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001 Sep 13;345(11):784-9. doi: 10.1056/NEJMoa001999.

  PMID: 11556297 BACKGROUND

• Yue H, Shan L, Bin L. The significance of OLGA and OLGIM staging systems in the risk assessment of gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2018 Jul;21(4):579-587. doi: 10.1007/s10120-018-0812-3. Epub 2018 Feb 19.

  PMID: 29460004 BACKGROUND

• Huang KK, Ramnarayanan K, Zhu F, Srivastava S, Xu C, Tan ALK, Lee M, Tay S, Das K, Xing M, Fatehullah A, Alkaff SMF, Lim TKH, Lee J, Ho KY, Rozen SG, Teh BT, Barker N, Chia CK, Khor C, Ooi CJ, Fock KM, So J, Lim WC, Ling KL, Ang TL, Wong A, Rao J, Rajnakova A, Lim LG, Yap WM, Teh M, Yeoh KG, Tan P. Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer. Cancer Cell. 2018 Jan 8;33(1):137-150.e5. doi: 10.1016/j.ccell.2017.11.018. Epub 2017 Dec 28.

  PMID: 29290541 BACKGROUND

• Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996 Oct;20(10):1161-81. doi: 10.1097/00000478-199610000-00001.

  PMID: 8827022 BACKGROUND

• Noguchi M. Racial factors cannot explain superior Japanese outcomes in stomach cancer. Arch Surg. 1997 Jan;132(1):99. doi: 10.1001/archsurg.1997.01430250101021. No abstract available.

  PMID: 9006560 BACKGROUND

• Filipe MI, Munoz N, Matko I, Kato I, Pompe-Kirn V, Jutersek A, Teuchmann S, Benz M, Prijon T. Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer. 1994 May 1;57(3):324-9. doi: 10.1002/ijc.2910570306.

  PMID: 8168991 BACKGROUND

• Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010 Jun;71(7):1150-8. doi: 10.1016/j.gie.2009.12.029. Epub 2010 Apr 9.

  PMID: 20381801 BACKGROUND

• Shah KA, Deacon AJ, Dunscombe P, Price AB. Intestinal metaplasia subtyping: evaluation of Gomori's aldehyde fuchsin for routine diagnostic use. Histopathology. 1997 Sep;31(3):277-83. doi: 10.1046/j.1365-2559.1997.2110847.x.

  PMID: 9354900 BACKGROUND

• Lee JWJ, Zhu F, Srivastava S, Tsao SK, Khor C, Ho KY, Fock KM, Lim WC, Ang TL, Chow WC, So JBY, Koh CJ, Chua SJ, Wong ASY, Rao J, Lim LG, Ling KL, Chia CK, Ooi CJ, Rajnakova A, Yap WM, Salto-Tellez M, Ho B, Soong R, Chia KS, Teo YY, Teh M, Yeoh KG. Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP). Gut. 2022 May;71(5):854-863. doi: 10.1136/gutjnl-2021-324057. Epub 2021 May 11.

  PMID: 33975867 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, buffy coat, plasma, tissue

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Gastroscopy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Khay Guan Yeoh, MBBS, MMed

  National University Hospital, Singapore

  STUDY CHAIR

• Jonathan WJ Lee, MBBS, MRCP

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 23, 2023
• Study Start: August 23, 2019
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2033
• Last Updated: April 18, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (3); KR (1); TW (1); US (1); HK (1); JP (1)