Condition or disease |
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To Evaluate the Sensitivity and Specificity of a Test Kit in Hong Kong |
Colorectal cancer (CRC) remains to be a leading cause of cancer mortality [1]. It induces a substantial financial burden in terms of healthcare utilization and quality-adjusted life years (QALY) lost [2]. Fecal Occult Blood Tests (FOBT) and colonoscopy were proven effective in reducing CRC mortality by 33% and 68%, respectively [3-5]. Both tests have been proposed as primary screening modalities for asymptomatic subjects by international guidelines and Asia Pacific consensus statements [6-8]. However, colonoscopy has a low compliance rate at approximately 20% in Chinese populations, and has been perceived by screening participants as invasive, expensive and inconvenient due to the need for bowel preparation [9, 10]. In addition, the accuracy of FOBT is limited and its adherence declined sharply over time [11, 12]. Hence, the recent decade witnessed a rapid development of non-invasive biomarkers to detect CRC.
Faecal-DNA test is a novel screening test for CRC, using molecular techniques to identify CRC-relevant biomarkers in stool. One of its toolkits, branded 'ColoGuard' (sDNA, Exact Sciences), was first approved by the FDA in 2014 for its application in clinical practice [13]. It consists of quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, and a hemoglobin immunoassay [13], which has been widely promoted in US. In 2016, it was endorsed by the United States Preventive Service Task Force (USPSTF) as one of the recommended screening tests [14].
Recently, a test kit named 'COLOSAFE' (or namedChang An Xin) has been developed as a faecal-DNA product targeted to improve diagnostic accuracy of CRC screening [15]. It is a stool test of methylated SDC2 for detection of CRC. This stool test of methylated SDC2 detected 81.1% of CRC and 58.2% of adenomas at a specificity of 93.3%. SDC2 is also named fibroglycan, encoding a type I trans-membrane heparansulfate proteoglycan. In certain cancers, hypermethylation of SDC2 had been reported. Recent studies showed that methylated SDC2 was detected at high frequency in blood from CRC patients [16, 17]. As tumor cells are exfoliated into the gut lumen earlier than vascular invasion when CRC develops [18], faecal sample could represent a more suitable specimen than plasma for detection of early cancer.
A recent study involving 1,200 subjects from 2015 to 2017 by the Sixth Affiliated Hospital of Sun Yat-sen University, Nanfang Hospital of Southern Medical University and Shandong Cancer Hospital showed that the 'COLOSAFE' test kit attained a sensitivity of 85% while maintaining a specificity of 98% (unpublished data). Because of its novelty, the 'COLOSAFEtest kit was recognized as a 'creative medical apparatus' by the National CFDA in March 2017. In June 2017, the project 'Screening and intervention research of Chinese CRC' (2017YFC 1308800) was launched with national key project for non-communicable disease control. Nevertheless, there are limitations with the design of the original study [15]. For instance, it involved a small, single-centre that recruited a homogeneous sample of individuals only. An important knowledge gap exists and additional clinical trials are required to further validate its diagnostic accuracy in other populations.
Study Type : | Observational |
Estimated Enrollment : | 400 participants |
Observational Model: | Case-Control |
Time Perspective: | Prospective |
Official Title: | The Diagnostic Accuracy of Using Faecal-DNA Test (COLOSAFE) for Colorectal Cancer Screening |
Actual Study Start Date : | February 11, 2019 |
Estimated Primary Completion Date : | January 1, 2020 |
Estimated Study Completion Date : | February 28, 2020 |
Group/Cohort |
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CRC cases
samples will be collected from subjects with known diagnosis of colorectal cancer
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Healthy cases
samples will be collected from healthy subjects with normal colonoscopy findings
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Cases with pathologies
samples will be collected from subjects whose colonoscopies showed other pathologies (e.g. inflammatory polyps, adenomas, diverticular diseases)
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Ages Eligible for Study: | 45 Years to 79 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
Exclusion Criteria:
Contact: Ming Yeung Ho | 2637 1398 | andrewho@cuhk.edu.hk | |
Contact: Yuen Tung Lam | 26370355 | thomaslam@cuhk.edu.hk |
Hong Kong | |
Prince of Wales Hospital | Recruiting |
Hong Kong, Hong Kong | |
Contact: Ming Yeung HO 26371398 andrewho@cuhk.edu.hk |
Tracking Information | |||||||||
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First Submitted Date | April 16, 2019 | ||||||||
First Posted Date | July 24, 2019 | ||||||||
Last Update Posted Date | July 24, 2019 | ||||||||
Actual Study Start Date | February 11, 2019 | ||||||||
Estimated Primary Completion Date | January 1, 2020 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures |
Accuracy of COLOSAFE [ Time Frame: 1 year ] Sensitivity, specificity, positive predictive value and negative predictive value in detection of CRC by COLOSAFE
|
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Original Primary Outcome Measures | Same as current | ||||||||
Change History | No Changes Posted | ||||||||
Current Secondary Outcome Measures | Not Provided | ||||||||
Original Secondary Outcome Measures | Not Provided | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title | The Diagnostic Accuracy of Using Faecal-DNA Test (COLOSAFE) for Colorectal Cancer Screening | ||||||||
Official Title | The Diagnostic Accuracy of Using Faecal-DNA Test (COLOSAFE) for Colorectal Cancer Screening | ||||||||
Brief Summary | To evaluate the sensitivity and specificity of the test kit "COLOSAFE' in Hong Kong | ||||||||
Detailed Description |
Colorectal cancer (CRC) remains to be a leading cause of cancer mortality [1]. It induces a substantial financial burden in terms of healthcare utilization and quality-adjusted life years (QALY) lost [2]. Fecal Occult Blood Tests (FOBT) and colonoscopy were proven effective in reducing CRC mortality by 33% and 68%, respectively [3-5]. Both tests have been proposed as primary screening modalities for asymptomatic subjects by international guidelines and Asia Pacific consensus statements [6-8]. However, colonoscopy has a low compliance rate at approximately 20% in Chinese populations, and has been perceived by screening participants as invasive, expensive and inconvenient due to the need for bowel preparation [9, 10]. In addition, the accuracy of FOBT is limited and its adherence declined sharply over time [11, 12]. Hence, the recent decade witnessed a rapid development of non-invasive biomarkers to detect CRC. Faecal-DNA test is a novel screening test for CRC, using molecular techniques to identify CRC-relevant biomarkers in stool. One of its toolkits, branded 'ColoGuard' (sDNA, Exact Sciences), was first approved by the FDA in 2014 for its application in clinical practice [13]. It consists of quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, and a hemoglobin immunoassay [13], which has been widely promoted in US. In 2016, it was endorsed by the United States Preventive Service Task Force (USPSTF) as one of the recommended screening tests [14]. Recently, a test kit named 'COLOSAFE' (or namedChang An Xin) has been developed as a faecal-DNA product targeted to improve diagnostic accuracy of CRC screening [15]. It is a stool test of methylated SDC2 for detection of CRC. This stool test of methylated SDC2 detected 81.1% of CRC and 58.2% of adenomas at a specificity of 93.3%. SDC2 is also named fibroglycan, encoding a type I trans-membrane heparansulfate proteoglycan. In certain cancers, hypermethylation of SDC2 had been reported. Recent studies showed that methylated SDC2 was detected at high frequency in blood from CRC patients [16, 17]. As tumor cells are exfoliated into the gut lumen earlier than vascular invasion when CRC develops [18], faecal sample could represent a more suitable specimen than plasma for detection of early cancer. A recent study involving 1,200 subjects from 2015 to 2017 by the Sixth Affiliated Hospital of Sun Yat-sen University, Nanfang Hospital of Southern Medical University and Shandong Cancer Hospital showed that the 'COLOSAFE' test kit attained a sensitivity of 85% while maintaining a specificity of 98% (unpublished data). Because of its novelty, the 'COLOSAFEtest kit was recognized as a 'creative medical apparatus' by the National CFDA in March 2017. In June 2017, the project 'Screening and intervention research of Chinese CRC' (2017YFC 1308800) was launched with national key project for non-communicable disease control. Nevertheless, there are limitations with the design of the original study [15]. For instance, it involved a small, single-centre that recruited a homogeneous sample of individuals only. An important knowledge gap exists and additional clinical trials are required to further validate its diagnostic accuracy in other populations. |
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Study Type | Observational | ||||||||
Study Design | Observational Model: Case-Control Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||||||
Biospecimen | Retention: Samples With DNA Description:
A case-control study will be performed to assess the sensitivity and specificity of the faecal-DNA test in a Hong Kong Chinese population. All subjects will receive both the faecal-DNA test and colonoscopy to calculate the above index.
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Sampling Method | Non-Probability Sample | ||||||||
Study Population | A total of 400 individuals aged 45-79 years will be consecutively recruited for this study. Among them, we aim to recruit 150 subjects with known diagnosis of CRC; 150 subjects with normal colonoscopy findings; and 100 subjects whose colonoscopies showed other pathologies (e.g. inflammatory polyps, adenomas, diverticular diseases). To enhance comparability of the cases and the controls, we aim to recruit these subjects in the same hospital (medical or surgical clinics of the Prince of Wales Hospital). Stool samples will be collected within 8 days to 3 months after the individuals received colonoscopy, but before any treatments, including surgery, chemotherapy, and radiotherapy. We aim to match cases and controls by their age and gender. | ||||||||
Condition | To Evaluate the Sensitivity and Specificity of a Test Kit in Hong Kong | ||||||||
Intervention | Not Provided | ||||||||
Study Groups/Cohorts |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status | Recruiting | ||||||||
Estimated Enrollment |
400 | ||||||||
Original Estimated Enrollment | Same as current | ||||||||
Estimated Study Completion Date | February 28, 2020 | ||||||||
Estimated Primary Completion Date | January 1, 2020 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 45 Years to 79 Years (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers | Yes | ||||||||
Contacts |
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Listed Location Countries | Hong Kong | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number | NCT04030637 | ||||||||
Other Study ID Numbers | Protocol_v21_20190110 | ||||||||
Has Data Monitoring Committee | Not Provided | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Responsible Party | Joseph JY SUNG, Chinese University of Hong Kong | ||||||||
Study Sponsor | Chinese University of Hong Kong | ||||||||
Collaborators | Not Provided | ||||||||
Investigators | Not Provided | ||||||||
PRS Account | Chinese University of Hong Kong | ||||||||
Verification Date | July 2019 |