Multitarget Stool FIT-DNA Study for Colorectal Cancer Early Screening in China (CLEAR-C)

Stool KRAS Mutation, BMP3/NDRG4 Methylation and FIT Panel Test for the Detection of Colorectal Advanced Neoplasia in High Risk Chinese Patients

The primary objective is to determine the diagnostic sensitivity and specificity of the newly developed multitarget FIT-DNA Colorectal Cancer (CRC) screening test (ColoClear) for detecting advanced neoplasia (including colorectal cancer and advanced adenomas) in high risk patients, using colonoscopy as the reference method. The secondary objective is to compare the screening performance of the multitarget FIT-DNA test with commercially available FIT (Fecal Immunochemical Test) assay in detecting advanced neoplasia.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Adenoma; Adenomatous Polyps; Advanced Adenoma
• Intervention / Treatment: Diagnostic test: Multitarget stool FIT-DNA test - ColoClear; Diagnostic test: FIT; Procedure: Colonoscopy

Detailed Description

The study will be carried out in 8 tier-3A hospitals throughout China. Patients who are at high risk of developing colorectal cancer and willing to conduct colonoscopy examination will be asked to collect stool sample prior to bowl preparation for multitarget FIT-DNA test and commercially available FIT assay. Colonoscopy and histopathologic examination are used as reference.

• Study Type: Observational
• Enrollment (Actual): 4758

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • The first affiliated hospital of Zhengzhou university
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The First Affiliated Hospital with Nanjing Medical University
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Taiyuan, Shanxi, China
      • Shanxi Provincial People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The Second Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with high risk of developing CRC and patients with confirmed CRC

Description

Inclusion Criteria:

• Willing to provide written consent
• Able to provide stool sample

For high risk CRC screening group:

• Scheduled for colonoscopy voluntarily or by physician prescription
• CRC high risk profile as defined below:
• History of FIT positivity
• Family history of CRC
• Any of two of the following clinical symptoms: chronic constipation/diarrhea, stool with mucous, chronic appendicitis, chronic bilary track diseases, mental stress

For CRC group:

• Confirmed CRC patients
• No prior treatment with chemotherapy, radiotherapy, and prior to any surgical procedures

Exclusion Criteria:

• Unwilling to provide stool samples
• FAP (familial adenomatous polyposis), Crohn's disease, ulcerative colitis
• Prior history of colonoscopy within the past 5 years and removal of lesions
• History of CRC
• other conditions deemed not suited for the study by investigators

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High risk CRC screening group; Prospective enrollment of subjects with pre-defined high risk factors for developing colorectal cancer	Diagnostic test: Multitarget stool FIT-DNA test - ColoClear; Multitarget stool FIT-DNA test; Diagnostic test: FIT; fecal immunochemical test; Procedure: Colonoscopy; diagnostic colonoscopy
CRC group; Retrospective enrollment of subjects with confirmed colorectal cancer	Diagnostic test: Multitarget stool FIT-DNA test - ColoClear; Multitarget stool FIT-DNA test; Diagnostic test: FIT; fecal immunochemical test; Procedure: Colonoscopy; diagnostic colonoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of the ColoClear screening test with comparison to colonoscopy	A diagnostic colonoscopy procedure is the reference method. Lesions will be confirmed as malignant by histopathologic examination. The DNA test includes molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, plus a hemoglobin immunoassay. A logistic-regression algorithm incorporating all the above parameters was deployed to compute a single composite score, with values of 165 or more considered to be positive. The tests were processed independently of colonoscopy procedure.	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the ColoClear screening test with comparison to FIT, with respect to advanced adenoma (AA) and CRC	A diagnostic colonoscopy procedure is the reference method. Lesions will be confirmed as malignant by histopathologic examination. The ColoClear and FIT test were performed on the same stool sample.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: New Horizon Health Technology Co., Ltd; Beijing Mingze Technology Co., Ltd.
• Investigators: Principal Investigator: Kefeng Ding, MD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2018
• Primary Completion (Actual): December 8, 2019
• Study Completion (Actual): September 13, 2020

Study Registration Dates

• First Submitted: February 20, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Neoplasms; Glandular and Epithelial; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colorectal Cancer; Adenoma; Colorectal Neoplasms; Colonic Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Rectal Diseases; Adenomatous Polyps; Advanced adenoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenoma; Adenomatous Polyps
• Other Study ID Numbers: CLEAR-C 2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No