The Implication of Plasma ctDNA Methylation Haplotypes in Detecting Colorectal Cancer and Adenomas

The Implication of Plasma Circulating Tumor DNA Methylation Haplotypes in Detecting Colorectal Cancer and Adenomas: a Multicenter, Cohort Study

This is a multicenter, clinical study. This study is to evaluate the sensitivity of plasma ctDNA methylation haplotypes in detecting colorectal cancer, adenoma and the specificity in healthy individuals.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Adenoma
• Intervention / Treatment: Diagnostic test: Next-generation sequencing (NGS)

Detailed Description

Colorectal cancer (CRC) is the third most common cancer worldwide, the second deadliest cancer in the United States. DNA methylation is a commonly used biomarker for non-invasive CRC detection in plasma. The low sensitivity of blood-based tests is due to several limitations of detecting ctDNA in early-stage cancer. We developed and validated a high-throughput methylation-based blood test highly sensitive for colorectal cancer and precancerous lesions. This previously established colorectal tumor-specific plasma ctDNA methylation markers (diagnostic model established by next-generation sequencing of gene loci methylation) had a high sensitivity in CRC patients and a high specificity in healthy individuals in a large retrospective sample study. This prospective, multicenter, clinical study is to further evaluate the sensitivity of plasma ctDNA methylation haplotypes in detecting colorectal cancer, adenoma and the specificity in healthy individuals.

• Study Type: Observational
• Enrollment (Actual): 1138

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy individuals and patients with stage I-IV colorectal cancer or adenomas must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent.

Description

Inclusion Criteria:

Healthy Individuals:

• Written informed consent must be obtained from healthy individuals to comply with the requirements of the study.
• Healthy individuals who received colonoscopy.

Patients with Colorectal Cancer or Adenomas:

• Male or female ≥ 18 years of age on the day of signing informed consent.
• Patients need to receive surgical resection or endoscopic resection.
• Patients must have histologically confirmed stage I-IV colorectal cancer or adenomas
• Patients must have a performance status of ≤1 on the ECOG Performance Scale.
• Written informed consent must be obtained from patient or patient's legal representative and ability for patient to comply with the requirements of the study.

Exclusion Criteria:

• Patients received adjuvant treatment prior to the surgical resection.
• Patients received blood transfusion two weeks before or during the surgical resection.
• Patients with unresected advanced colorectal adenoma.
• Patients who are positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C.
• Patients who are pregnant.
• Patients who are alcoholic or drug abusers.
• Patients with a history or current evidence of any condition or abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy individuals	Diagnostic test: Next-generation sequencing (NGS); NGS test for colorectal tumor-specific plasma ctDNA methylation markers prior to endoscopy
Patients with Colorectal cancer; Stage I-IV colorectal cancer patients	Diagnostic test: Next-generation sequencing (NGS); NGS test for colorectal tumor-specific plasma ctDNA methylation markers prior to endoscopy
Patients with Colorectal Adenomas	Diagnostic test: Next-generation sequencing (NGS); NGS test for colorectal tumor-specific plasma ctDNA methylation markers prior to endoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	The sensitivity of plasma ctDNA methylation haplotypes in detecting colorectal cancer and adenoma	2 years
Specificity	The specificity of plasma ctDNA methylation haplotypes in healthy individuals	2 years

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Southern Medical University, China

Publications and helpful links

General Publications

• Mo S, Dai W, Wang H, Lan X, Ma C, Su Z, Xiang W, Han L, Luo W, Zhang L, Wang R, Zhang Y, Zhang W, Yang L, Lu R, Guo L, Zheng Y, Huang M, Xu Y, Liang L, Cai S, Cai G. Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: A multicentre cohort study. EClinicalMedicine. 2022 Nov 3;55:101717. doi: 10.1016/j.eclinm.2022.101717. eCollection 2023 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2010
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (Actual): November 9, 2018

Study Record Updates

• Last Update Posted (Actual): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 9, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Adenomas; ctDNA Methylation Haplotypes
• 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
• Other Study ID Numbers: FDCRCA-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No