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Validation of Colon Biomarkers for the Early Detection of Colorectal Adenocarcinoma (GLNE010)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01511653
Recruitment Status : Completed
First Posted : January 18, 2012
Last Update Posted : January 18, 2020
Early Detection Research Network
Information provided by (Responsible Party):
Dean Brenner, University of Michigan

Brief Summary:
The investigators are undertaking a multi-center, 13000 subject validation study of several biomarkers for early detection of colon cancer. There are stool based biomarkers and blood based biomarkers being validated in this study. The biomarkers will be compared with colonoscopy and with FIT (fecal immunohistochemistry) tests which are the current standards for colon cancer screening. This is an NCI-early Detection Research Network funded project. The population targeted for this study are those persons undergoing colonoscopy for screening. Prior to colonoscopy or even prepping for colonoscopy, subjects will provide blood and stool samples as well as specific data regarding their GI and general medical history and concomitant medications. If subjects are interested in participating, arrangements will be made to see them. The informed consent process will take place, blood will be obtained, data will be obtained, and the stool kit described and given to the subject to take home. Stool samples will be sent back to the University of Michigan using prepaid mailing labels.

Condition or disease
Colon Cancer Rectal Cancer

Detailed Description:

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).

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Study Type : Observational
Estimated Enrollment : 13000 participants
Observational Model: Case-Control
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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
Two 10 ml red top (serum) tubes Three 10 ml purple top (EDTA)tubes 25 ml of urine 2 Fecal Immunohistochemical Tests (FIT) Stool

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
13000 asymptomatic subjects aged 50-80 undergoing routine colonoscopic screening for colorectal cancer from community and major medical center outpatient settings across multiple centers and consortia will be recruited.

Inclusion Criteria:

  • Adults 40*+ undergoing a first time colonoscopy for screening OR
  • Positive guaiac-based occult blood or fecal immunochemical test (e.g. FOBT, FIT) in the past 12 months (365 days)
  • Willing to sign informed consent
  • Able to physically tolerate removal of 50 ml of blood
  • Willing to collect 2 stool samples

(*age 60 and up in U.S., 50 and up outside US)

Exclusion Criteria:

  • Inability to provide informed consent
  • History of Inflammatory Bowel Disease
  • Overt rectal bleeding within 1 month (30 days) (including due to suspected hemorrhoids)
  • Undergone resection of the colon for any indication
  • Subjects with known HIV or chronic viral hepatitis (Hepatitis B and C)
  • Subjects with known or suspected HNPCC (Lynch Syndrome) or FAP

    • Any cancer within 5 years of enrollment except any of the following:
    • Squamous cell carcinoma of the skin or Basal cell carcinoma of the skin
    • Carcinoma in situ of the cervix, Stages Ia or Ib invasive squamous cell carcinoma of the cervix treated by surgery only. (Excluded if had pelvic radiation)
    • Stage , 0, I or Ia Grade 1 adenocarcinoma of the endometrium treated with surgery

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01511653

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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
Canada, Alberta
University of Calgary-Colon Cancer Screening Centre
Calgary, Alberta, Canada, T2N 4Z6
German Cancer Research Center (DKFZ)
Heidelberg, Germany, 69120
Sponsors and Collaborators
University of Michigan
Early Detection Research Network
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Principal Investigator: Dean E Brenner, M.D. University of Michigan
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Responsible Party: Dean Brenner, Professor Internal Medicine, University of Michigan Identifier: NCT01511653    
Obsolete Identifiers: NCT01585363
Other Study ID Numbers: GLNE010
First Posted: January 18, 2012    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dean Brenner, University of Michigan:
screening colonoscopy
colon cancer early detection
rectal cancer early detection
colorectal cancer prevention
biomarker validation
Additional relevant MeSH terms:
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Rectal Neoplasms
Colonic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases