Validation of Colon Biomarkers for the Early Detection of Colorectal Adenocarcinoma (GLNE010)
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|ClinicalTrials.gov Identifier: NCT01511653|
Recruitment Status : Completed
First Posted : January 18, 2012
Last Update Posted : January 18, 2020
|Condition or disease|
|Colon Cancer Rectal Cancer|
The goal of this trial is to estimate the sensitivity and specificity of stool vimentin methylation, serum galectin-3 ligand, and fecal immunochemical testing for colorectal adenocarcinoma, or 2) screen relevant neoplasms (high-grade dysplasia or adenoma with ≥25% villous histologic features or adenoma measuring ≥1 cm in the greatest dimension or sessile serrated polyps measuring 1 cm or more in diameter) as single markers and in combination. Asymptomatic subjects undergoing a colonoscopic procedure for screening for colorectal cancer are eligible. Patients who have a first or second positive fecal immunochemical test, a positive stool guaiac test or a positive Cologuard test are eligible. Up to 2,500 stool blood or Cologuard positive subjects will be recruited on this protocol. Up to an additional 1,000 subjects who have not had previous FIT tests will be recruited. Subjects with a negative stool blood or Cologuard test are not eligible for enrollment. Subjects will meet with research staff prior to initiation of any colonoscopic preparative procedure. After completing informed consent, they will complete Early Detection Research Network (EDRN) data element forms. Blood and urine will be obtained following EDRN standard operating procedures (SOPs). Subjects will be provided with kits to collect stool samples for fecal immunochemical test (FIT) and processing for stool based biomarkers. The collected samples will be shipped to the Central Laboratory at the University of Michigan or German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, Germany where the stool will be homogenized, aliquoted, and stored at the Umiversity of Michigan CLASS laboratories . The FIT tests will be sent to the Central Laboratory at the University of Michigan or to DKFZ for quantitative analysis following standard operating procedures provided by Eiken Chemical Company. Data from the screening colonoscopy will be obtained. One year after colonoscopy, subjects will be contacted to determine if they have had a neoplastic colorectal diagnosis or other neoplastic events. Data management and protocol coordination will be performed by the Data Management and Coordinating Center (DMCC) of the EDRN along with the GLNE Prevention Research Base at the University of Michigan and will include a Web-based front end and relational database backend, with biosample tracking (VSIMS). Biosamples will be managed in a high quality repository facility at the University of Michigan.
We will estimate sensitivities and specificities and the corresponding confidence intervals of the stool DNA tests and serum/plasma tests for detection of invasive colorectal neoplasms and for screen relevant neoplasias (Aim 1). We will then test the primary hypothesis to confirm the clinical accuracy of a particular biomarker test or panel (Aim 2). The specific primary hypothesis will be defined prior to data analysis based on state of the art information available at that time about candidate biomarkers and tests. Several specific examples of potential primary hypotheses are given to justify study sample size. Finally, several alternative tests and multi-marker panels will be evaluated. (Aim 3). In secondary analysis, we will (a) provide measures of diagnostic accuracy standardized to the age and gender distribution of US population and (b) assess the effect of subject heterogeneity on the marker performance. A primary objective is to establish an archive of appropriately preserved stool, serum, plasma and DNA human biospecimens to be used by EDRN-approved investigators for future validation and biomarker discovery research (Aim 4).
|Study Type :||Observational|
|Estimated Enrollment :||13000 participants|
|Official Title:||Validation and Comparison of Biomarkers for the Early Detection of Colorectal Adenocarcinoma|
|Actual Study Start Date :||October 2011|
|Actual Primary Completion Date :||April 2019|
|Actual Study Completion Date :||April 2019|
- Measure the sensitivity of a blood based panel of biomarkers relative to fecal immunochemical testing [ Time Frame: 12 weeks from enrollment to completion of colonoscopy ]Test the hypothesis that sensitivity of stool vimentin methylation and/ the blood based panel (serum galectin-3 ligand, CEA, methylated genes BCAT1/IKZF1, Hypomethylated LINE1 from circulating cell free DNA) when combined with fecal immunochemical testing (FIT) will significantly improve the sensitivity of FIT for the detection of colorectal adenocarcinoma, and maintain specificity greater than 0.80.
- To measure the specificity of a blood based panel of biomarkers relative to fecal immunochemical testing [ Time Frame: 12 weeks from enrollment to completion of colonoscopy ]To test the hypothesis that blood based panel (for example, serum galectin-3 ligand, CEA, methylated genes BCAT1/IKZF1, Hypomethylated LINE1 from circulating cell free DNA), at the same sensitivity of that for fecal immunochemical testing (FIT) for the detection of colorectal adenocarcinoma, has a specificity greater than 0.55 with an anticipated specificity ≥ 0.70.
- To measure the sensitivity and specificity of a combined panel of blood and stool based biomarkers for the detection of colorectal cancer [ Time Frame: 12 weeks from enrollment to completion of colonoscopy ]To test the hypothesis that stool vimentin methylation, the blood based panel (serum galectin-3 ligand, CEA, methylated genes BCAT1/IKZF1, Hypomethylated LINE1 from circulating cell free DNA), when combined will improve the detection of colorectal adenocarcinoma: at sensitivity ≥0.98 it will have a specificity significantly greater than 0.55.
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01511653
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55113|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Pennsylvania|
|Penn State College of Medicine|
|Hershey, Pennsylvania, United States, 17033|
|United States, Texas|
|M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Washington|
|University of Washington|
|Seattle, Washington, United States, 98195|
|University of Calgary-Colon Cancer Screening Centre|
|Calgary, Alberta, Canada, T2N 4Z6|
|German Cancer Research Center (DKFZ)|
|Heidelberg, Germany, 69120|
|Principal Investigator:||Dean E Brenner, M.D.||University of Michigan|