A Stool DNA-based SDC2 Methylation Test for the Early Detection of Colorectal Cancer

Study Overview
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Brief Summary
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The primary objective of this clinical trial is to determine the sensitivity and specificity of the EarlyTect® CRC test for detecting CRC, using colonoscopy as the reference method. The secondary objective is to compare the clinical performance of EarlyTect® CRC test with a commercially available Fecal Immunochemical Test (FIT), with respect to CRC. By histopathological examination, lesions identified during colonoscopy will be confirmed as malignant or precancerous by histological examination.

Detailed Description
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A multicenter, single-blind, prospective clinical trial is being conducted to evaluate the clinical performance of EarlyTect® CRC test. Subjects who are at high-risk (Asia Pacific Colorectal Screening Score ≥4.0) of developing CRC who are eligible for inclusion criteria will be asked to collect a stool sample and EarlyTect® CRC and FIT tests will be performed. For confirmation of the diagnosis and tumor staging, representative histopathology slides obtained from curative surgery and representative histopathology slides from tissue biopsied or excised during colonoscopy may be retrieved and examined by the central pathology laboratory. Methylation status of SDC2 in stool DNA is measured by a highly accurate and sensitive real time PCR that employs Linear Target Enrichment (LTE) and quantitative Methylation-Specific PCR (qMSP)(LTE-qMSP).

Official Title
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A Multicenter, Single-blind, Prospective Clinical Trial to Evaluate the Clinical Performance of EarlyTect® CRC Test for the Early Detection of Colorectal Cancer in the Stool DNA From High-risk Group

Conditions
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Colorectal Cancer, Advanced Colorectal Neoplasm, Advanced Adenomas, Non-neoplastic Polyps, Non-advanced Adenomas

Intervention / Treatment
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* Device: EarlyTect® CRC test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects enrolled into the study must meet the following criteria: Individuals who agree to voluntarily sign an informed consent prior to the initiation of screening Adults aged ≥ 40 years Subjects who are at high-risk (Asia Pacific Colorectal Screening (APCS) Score: 4.0 7.0) of developing CRC Subjects who are able and willing to undergo colonoscopy screening within 12 months of consent among individuals who reserved a visit in the division of gastroenterology or health check-up. Exclusion Criteria: Subjects will be excluded from enrolling into the study if any of the following criteria are met: Individuals who do not agree to voluntarily sign an informed consent prior to the initiation of screening Adults aged < 40 years Subjects who are not at high-risk (APCS Score ≤ 3.0) of developing CRC Subjects who will not undergo colonoscopy screening within 12 months of consent Subjects who have had a positive FIT or fecal occult blood test within the previous 2 weeks Colorectal cancer patients who did not underwent curative treatment Subjects who have had a prior history of colorectal resection Subjects who have had overt rectal bleeding or melena within the previous 2 weeks Subjects who have a family history or a prior history of hereditary CRC or colorectal neoplasm: Lynch syndrome (HNPCC), familial adenomatous polyposis, MUTYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers syndrome, and serrated polyposis syndrome, etc. Subjects who have inflammatory bowel diseases including Crohn's disease, ulcerative colitis or Behcet disease Subjects who participated in any interventional clinical study within the previous 30 days Subject has any condition which, in the opinion of the medical staff should preclude participation in the study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort<br>Subjects who are at high-risk (Asia Pacific Colorectal Screening Score ≥4.0) of developing CRC aged ≥40 | Device: EarlyTect® CRC test<br>* A highly accurate and sensitive real time PCR employing Linear Target Enrichment and Quantitative Methylation-Specific PCR (LTE/qMSP) for measuring SDC2 methylation in stool DNA to detect CRC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of the EarlyTect® CRC test for detecting CRC compared to the colonoscopy, both in terms of detecting CRC. | The reference method is the colonoscopy, and lesions will be assessed histopathologically. EarlyTect® CRC test includes a measurement of SDC2 methylation and COL2A1 as a DNA control. SDC2 methylation in stool DNA will be assessed quantitatively by LTE/qMSP. The results will be dichotomized by the CT (cycle threshold) cutoff value as either positive or negative. Sensitivity = 100*(positive SDC2 methylation test/positive colonoscopy), Specificity = 100*(negative SDC2 methylation test/negative colonoscopy). | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of EarlyTect® CRC for detecting advanced colorectal adenoma (Adenomas ≥1.0 cm, villous adenomas or high-grade dysplasia) | Sensitivity for detecting adenomas ≥1.0 cm Sensitivity of EarlyTect® CRC for detecting villous adenomas Sensitivity of EarlyTect® CRC for detecting high-grade dysplasia | 18 months | 
| Sensitivity of EarlyTect® CRC for detecting advanced colorectal neoplasm | Sensitivity for detecting adenomas ≥1.0 cm | 18 months | 
| Sensitivity of EarlyTect® CRC for detecting non-advanced adenomas | Sensitivity for detecting non-adenomas <1.0 cm | 18 months | 
| Sensitivity and specificity of combined FIT and EarlyTect® CRC tests in detecting CRC | Sensitivity and specificity of combined FIT and EarlyTect® CRC tests in detecting CRC | 18 months | 
| Sensitivity of EarlyTect® CRC for detecting advanced colorectal serrated lesions | Sensitivity of EarlyTect® CRC for detecting advanced colorectal serrated lesions | 18 months | 
| Clinical specificity of EarlyTect® CRC when patients with non-advanced adenomas and non-advanced colorectal serrated lesions are included in control group | Clinical specificity of EarlyTect® CRC when patients with non-advanced adenomas and non-advanced colorectal serrated lesions are included in control group | 18 months | 
| Clinical sensitivity of the EarlyTect® CRC for detecting Tis | Clinical sensitivity of the EarlyTect® CRC for detecting colorectal cancer with Tis | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, SDC2, Methylation biomarker, EarlyTect® CRC test, Stool