Comparison of Diagnostic Sensitivity Between ctDNA Methylation and CEA in Colorectal Cancer

NCT ID: NCT05558436

Last Updated: 2024-05-10

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

ACTIVE_NOT_RECRUITING

Total Enrollment

662 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-01

Study Completion Date

2024-12-31

Brief Summary

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This is a prospective diagnostic study. This study is to compare the performance between circulating tumor DNA (ctDNA) methylation and carcinoembryonic antigen (CEA) in detecting colorectal tumor. Firstly, based on the identification of differential ctDNA methylation biomarkers, the diagnostic model is established and the diagnostic performance was compared with that of CEA. Secondly, the stage stratification model was established preliminarily based on differential ctDNA methylation biomarkers and the performance was also compared with that of CEA.

Detailed Description

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Colorectal cancer (CRC) is the third most common cancer worldwide, the second deadliest cancer. It is reported that patients prefer non-invasive methods rather than invasive methods for the detection of CRC. Carcinoembryonic antigen (CEA) is commonly employed in clinical practice for early detection of CRC, but it is limited for its low sensitivity, which is around 30%-40%. DNA methylation is a commonly used biomarker for non-invasive tumor detection in plasma. We aim to develop and validate a ctDNA methylation-based blood test for CRC diagnosis based on genome-wide methylation detection. There are two steps in the study. Firstly, this prospective study aims to identify colorectal tumor differential circulating tumor DNA (ctDNA) methylation biomarkers, establish the diagnostic model. Secondly, we performed a preliminary study to stratify early-stage and advanced-stage disease based on the differential biomarkers.

Conditions

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Colorectal Tumor

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Case group

Patients with colorectal cancer and advanced adenoma.

Genome-wide methylation profiling

Intervention Type DIAGNOSTIC_TEST

Detection for colorectal tumor-specific ctDNA methylation biomarkers

Control group

Healthy participants and patients with benign colorectal disease.

Genome-wide methylation profiling

Intervention Type DIAGNOSTIC_TEST

Detection for colorectal tumor-specific ctDNA methylation biomarkers

Interventions

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Genome-wide methylation profiling

Detection for colorectal tumor-specific ctDNA methylation biomarkers

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

Case group

* Patients must have histologically confirmed colorectal cancer or advanced adenoma.
* Patients need to receive surgical resection or endoscopic resection.
* Patients have a performance status of ≤1 on the ECOG Performance Scale.
* Written informed consent must be obtained.

Control group

* Written informed consent must be obtained.
* Individuals must receive colonoscopy.

Exclusion Criteria

* Patients received tumor treatment prior to the drawn of blood sample, including surgical resection, neoadjuvant chemoradiotherapy and targeted therapy.
* Patients received antibiotics regularly.
* Patients received blood transfusion two weeks before the drawn of blood sample.
* Patients with indications of emergency surgery, including bleeding, obstruction and perforation.
* Patients who are positive for Human Immunodeficiency Virus (HIV).
* Patients with abnormal liver and kidney function.
* Patients with the history of other malignancies, inflammatory bowel disease and Lynch syndrome.
* Patients who are pregnant or breastfeeding.
* Alcoholic or drug abusers.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jun Yan, M.D., Ph.D.

Role: STUDY_CHAIR

Nanfang Hospital, Southern Medical University

Locations

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Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

Site Status

Countries

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China

References

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Reference Type BACKGROUND
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Adler A, Geiger S, Keil A, Bias H, Schatz P, deVos T, Dhein J, Zimmermann M, Tauber R, Wiedenmann B. Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany. BMC Gastroenterol. 2014 Oct 17;14:183. doi: 10.1186/1471-230X-14-183.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Kanwal R, Gupta K, Gupta S. Cancer epigenetics: an introduction. Methods Mol Biol. 2015;1238:3-25. doi: 10.1007/978-1-4939-1804-1_1.

Reference Type BACKGROUND
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Shen SY, Singhania R, Fehringer G, Chakravarthy A, Roehrl MHA, Chadwick D, Zuzarte PC, Borgida A, Wang TT, Li T, Kis O, Zhao Z, Spreafico A, Medina TDS, Wang Y, Roulois D, Ettayebi I, Chen Z, Chow S, Murphy T, Arruda A, O'Kane GM, Liu J, Mansour M, McPherson JD, O'Brien C, Leighl N, Bedard PL, Fleshner N, Liu G, Minden MD, Gallinger S, Goldenberg A, Pugh TJ, Hoffman MM, Bratman SV, Hung RJ, De Carvalho DD. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature. 2018 Nov;563(7732):579-583. doi: 10.1038/s41586-018-0703-0. Epub 2018 Nov 14.

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Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, Fu X, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu JK, Hao X, Zhang K. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. 2017 Nov;16(11):1155-1161. doi: 10.1038/nmat4997. Epub 2017 Oct 9.

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Xie H, Mahoney DW, Foote PH, Burger KN, Doering KA, Taylor WR, Then SS, Cao X, McGlinch M, Berger CK, Wu TT, Hubbard JM, Allawi HT, Kaiser MW, Lidgard GP, Ahlquist DA, Kisiel JB. Novel Methylated DNA Markers in the Surveillance of Colorectal Cancer Recurrence. Clin Cancer Res. 2021 Jan 1;27(1):141-149. doi: 10.1158/1078-0432.CCR-20-2589. Epub 2020 Oct 7.

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Cai G, Cai M, Feng Z, Liu R, Liang L, Zhou P; ColonAiQ Group; Zhu B, Mo S, Wang H, Lan X, Cai S, Xu Y, Wang R, Dai W, Han L, Xiang W, Wang B, Guo W, Zhang L, Zhou C, Luo B, Li Y, Nie Y, Ma C, Su Z. A Multilocus Blood-Based Assay Targeting Circulating Tumor DNA Methylation Enables Early Detection and Early Relapse Prediction of Colorectal Cancer. Gastroenterology. 2021 Dec;161(6):2053-2056.e2. doi: 10.1053/j.gastro.2021.08.054. Epub 2021 Sep 4. No abstract available.

Reference Type BACKGROUND
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Liang N, Li B, Jia Z, Wang C, Wu P, Zheng T, Wang Y, Qiu F, Wu Y, Su J, Xu J, Xu F, Chu H, Fang S, Yang X, Wu C, Cao Z, Cao L, Bing Z, Liu H, Li L, Huang C, Qin Y, Cui Y, Han-Zhang H, Xiang J, Liu H, Guo X, Li S, Zhao H, Zhang Z. Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning. Nat Biomed Eng. 2021 Jun;5(6):586-599. doi: 10.1038/s41551-021-00746-5. Epub 2021 Jun 15.

Reference Type BACKGROUND
PMID: 34131323 (View on PubMed)

Other Identifiers

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NFEC-2022-245

Identifier Type: -

Identifier Source: org_study_id

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