A Study on a Blood-based Dual-target Test for CRC Detection

Colorectal Cancer Clinical Trial

Official title:

Validation of a ctDNA Methylation-based Dual-target Test for the Detection of Colorectal Cancer: a Multicenter Clinical Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05508503
• Other study ID #: 2020CRC-cfDNA
• Status: Completed
• Start date: October 21, 2022
• Est. completion date: August 11, 2023

Study information

• Verified date: February 2024
• Source: Changhai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To evaluate the effectiveness and accuracy of the ctDNA dual-target test kit in a large case-control cohort for the detection of colorectal cancer and advanced adenomas.

Description:

Usually, colorectal cancers (CRCs) diagnosed in their early stages are curable, especially precancerous lesions (adenomas, polyps) that can be removed during a colonoscopy.However, due to low patient compliance and limited resources, colonoscopy is not feasible for screening the average-risk population. gFOBT/FIT are limited by their low sensitivity and high false-positive rate. Compared to colonoscopy and stool DNA tests, blood-based methylation tests showed greater patient compliance and convenience. Hypermethylated NTMT1 and MAP3K14-AS1 were found in multiple cohorts of CRC samples in our previous study. In this study, we aimed to evaluate the effectiveness and accuracy of the ctDNA dual-target(NTMT1 and MAP3K14-AS1) test kit in 5 tertiary hospitals around china for the detection of colorectal cancer and advanced adenomas. Fecal immunochemical test (FIT) will also privided to participants in the study. Sanger sequencing would be performed to evalute the accuracy of the dual-target methylation detection test kit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1378
• Est. completion date: August 11, 2023
• Est. primary completion date: August 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Inclusion Criteria for CRC group(=30%) 1)Patients with colorectal cancer 2)Follow-up sample subjects: Subjects who underwent resection of colorectal cancer lesions.

2. Inclusion Criteria for Control group(=70%) Health volunteer, or subject with other diseases or physiological conditions other than colorectal cancer, including but not limited to gastritis, gastric cancer, esophagitis, rheumatoid arthritis, prostate cancer, microbes (inflammation patients), gastrointestinal bleeding, drugs (typical digestive tract medication) Population), neuroendocrine cancer, squamous cell carcinoma (squamous squamous cell carcinoma, esophageal squamous cell carcinoma);

Exclusion Criteria:

1. Patients who had undergone radical resection of bowel cancer (except for postoperative follow-up) and those who had received anti-tumor therapy such as radiotherapy/chemotherapy;

2. Colorectal cancer or colorectal adenoma with other malignancies;

3. Postoperative follow-up patients of colorectal cance with distant metastasis;

4. The sample size collected did not meet the detection requirements;

5. Other patients who are considered unsuitable for this study (such as pregnancy, high blood pressure, heart disease, etc., who are not suitable for colonoscopy due to physical condition).

Related Conditions & MeSH terms

• Adenoma
• Colorectal Adenoma
• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Diagnostic Test:
• Test of methylated NTMT1 and MAP3K14-AS1
A dual-target test kit to detect methylated NTMT1 and MAP3K14-AS1 in blood samples.
• FIT
Fecal immunochemical test(optional)

Locations

Country	Name	City	State
China	Changhai Hospital	Shanghai	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
Changhai Hospital	Henan Provincial People's Hospital, Qilu Hospital of Shandong University, The Second Hospital of Hebei Medical University, Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

References & Publications (5)

Cao Y, Zhao G, Yuan M, Liu X, Ma Y, Cao Y, Miao B, Zhao S, Li D, Xiong S, Zheng M, Fei S. KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer. Front Oncol. 2021 Jan 29;10:621295. doi: 10.3389/fonc.2020.621295. eCollection 2020. — View Citation

Chen H, Li N, Ren J, Feng X, Lyu Z, Wei L, Li X, Guo L, Zheng Z, Zou S, Zhang Y, Li J, Zhang K, Chen W, Dai M, He J; group of Cancer Screening Program in Urban China (CanSPUC). Participation and yield of a population-based colorectal cancer screening prog — View Citation

Oster B, Thorsen K, Lamy P, Wojdacz TK, Hansen LL, Birkenkamp-Demtroder K, Sorensen KD, Laurberg S, Orntoft TF, Andersen CL. Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas. Int J Cancer. 2011 Dec 15;129(12):2855-66. doi: 10.1002/ijc.25951. Epub 2011 Apr 1. — View Citation

Scholer LV, Reinert T, Orntoft MW, Kassentoft CG, Arnadottir SS, Vang S, Nordentoft I, Knudsen M, Lamy P, Andreasen D, Mortensen FV, Knudsen AR, Stribolt K, Sivesgaard K, Mouritzen P, Nielsen HJ, Laurberg S, Orntoft TF, Andersen CL. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. doi: 10.1158/1078-0432.CCR-17-0510. Epub 2017 Jun 9. — View Citation

Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev. 2016 Sep;35(3):347-76. doi: 10.1007/s10555-016-9629-x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity	Sensitivity (for CRC and\or advanced precancerous neoplasm) of this blood-based methylation dual-target test. A diagnostic colonoscopy procedure is the reference method. Lesions will be confirmed as malignant or precancerous by histopathologic examination. Other clinically acceptable diagnostic criteria for non-intestinal diseases.	Through study completion, an average of 1 year.
Primary	Specificity	Specificity (for CRC and\or advanced precancerous neoplasm) of this blood-based methylation dual-target test. A diagnostic colonoscopy procedure is the reference method. Lesions will be confirmed as malignant or precancerous by histopathologic examination. Other clinically acceptable diagnostic criteria for non-intestinal diseases.	Through study completion, an average of 1 year.
Primary	Accuracy	Accuracy of the kit for methylation detection. Validation of the methylation status of MTNT1 and MAP3K14-AS1 by Sanger sequencing.	Through study completion, an average of 1 year.
Secondary	Combined sensitivity	Sensitivity when combined the blood-based methylation dual-target test with FIT	Through study completion, an average of 1 year.
Secondary	Combined specificity	Specificity when combined the blood-based methylation dual-target test with FIT	Through study completion, an average of 1 year.