An Evaluation of a Multi-target Stool DNA (Mt-sDNA) Test, Cologuard, for CRC Screening in Individuals Aged 45-49 and at Average Risk for Development of Colorectal Cancer: Act Now

The primary objective is to confirm the specificity of a multi-target stool DNA test (mt-sDNA), Cologuard, in an average risk population, ages 45-49.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Colonoscopy; Diagnostic test: mt-sDNA screening test

Detailed Description

Subjects aged 45-49 at average risk for development of CRC will be enrolled. Subjects will complete the mt-sDNA screening test (Cologuard) followed by completion of a screening colonoscopy. The results of the mt-sDNA screening test (Cologuard) will not be provided to investigators for clinical management of study subjects. Personnel performing the colonoscopy and producing the resulting report and personnel performing histopathological review of tissue (if applicable) will remain blinded to the results of the mt-sDNA screening test (Cologuard) result.

• Study Type: Observational
• Enrollment (Actual): 983

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Camarillo, California, United States, 93012
      • Ventura County Gastroenterology
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
    • Oxnard, California, United States, 93030
      • FocilMed
    • Palm Springs, California, United States, 92262
      • Desert Oasis Healthcare Medical Group
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Gastroenterology Associates of Fairfield County
    • New Haven, Connecticut, United States, 06520
      • Yale University Section of Digestive Diseases and Liver Diseases
  • Florida
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research, LLC
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System Evanston Hospital
    • Oak Lawn, Illinois, United States, 60453
      • DM Clinical Research- Southwest Gastroenterology
  • Indiana
    • Evansville, Indiana, United States, 47725
      • Deaconess Clinic- Mt. Pleasant
    • Indianapolis, Indiana, United States, 46202
      • Indiana University, Eskanazi Hospital
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic- Gateway
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County ClinTrials, LLC
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • New Orleans Research Institute
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners, LLC
    • Shreveport, Louisiana, United States, 71103
      • Louisiana Research Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Elkridge, Maryland, United States, 21075
      • Centennial Medical Group
    • Rockville, Maryland, United States, 20850
      • Capitol Research
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • Binghamton, New York, United States, 13901
      • United Medical Associates
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology & Hepatology, PLLC
    • Wilmington, North Carolina, United States, 28403
      • Wilmington Gastroenterology Associates
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Massillon, Ohio, United States, 44647
      • Family Practice Center of Wooster, Inc./Clinical Trial Developers
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
    • Wooster, Ohio, United States, 44691
      • Comprehensive Internal Medicine, Inc.
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Gastroenterology Associates, PA
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research, PLLC
  • Texas
    • Austin, Texas, United States, 78726
      • Austin Regional Clinic
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center- McGovern Medical School
    • Houston, Texas, United States, 77070
      • DM Clinical Research- PCP for Life
  • Virginia
    • Suffolk, Virginia, United States, 23434
      • Virginia Gastroenterology Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects 45-49 years of age who are at average risk for development of CRC. 942 subjects are targeted to enroll.

Description

Inclusion Criteria:

Subjects must meet the following criteria to be eligible for the study:

1. Subject is at average risk for development of CRC.
2. Subject is able and willing to undergo a screening colonoscopy.
3. Subject is ≥ 45 and ≤ 49 years of age at the time of enrollment.
4. Subject is willing and able to sign informed consent.
5. Subject is able and willing to provide stool sample(s) according to written instructions provided.

Exclusion Criteria:

1. Subject has a history of CRC or adenoma.
2. Subject has ≥2 first-degree relatives who have been diagnosed with CRC
3. Subject has one first-degree relative with CRC diagnosed before the age of 60.
4. Subject has any of the following: Overt rectal bleeding, e.g., hematochezia or melena within the previous 30 days (blood on toilet paper, after wiping, does not constitute rectal bleeding). Positive fecal occult blood test or FIT within the previous six (6) months. Subject has had a previous colonoscopy. Subject has undergone any double-contrast barium enema, virtual (CT-based) colonoscopy, or flexible sigmoidoscopy within the previous five (5) years.
5. Subject has a diagnosis or personal history of any of the following conditions, including: Familial adenomatous polyposis (also referred to as "FAP", including attenuated FAP and Gardner's syndrome). Hereditary non-polyposis CRC syndrome (also referred to as "HNPCC" or "Lynch Syndrome").Other hereditary cancer syndromes including but are not limited to Peutz-Jeghers Syndrome, MYH-Associated Polyposis (MAP), Turcot's (or Crail's) Syndrome, Cowden's Syndrome, Juvenile Polyposis, Neurofibromatosis and Familial Hyperplastic Polyposis.
6. Subject has a family history of: Familial adenomatous polyposis (also referred to as "FAP"), Hereditary non-polyposis CRC syndrome (also referred to as "HNPCC" or "Lynch Syndrome").
7. Subjects with Cronkhite-Canada Syndrome.
8. Subject has a diagnosis of inflammatory bowel disease (IBD) including chronic ulcerative colitis (CUC) and Crohn's disease.
9. Subject has a history of aerodigestive tract cancer.
10. Subject has had a prior colorectal resection for any reason other than sigmoid diverticular disease.
11. Subject has any condition that in the opinion of the investigator should preclude participation in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subject aged 45-49 with Average CRC Risk; Subject aged 45-49 with average risk for development of CRC.	Procedure: Colonoscopy; Subjects will undergo a screening colonoscopy.; Diagnostic test: mt-sDNA screening test; Stool samples will be collected by the subject for the mt-sDNA screening test.; Other Names: Cologuard

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specificity of the Multi-target Stool DNA Test in Average Risk Population, Ages 45-49	An optical colonoscopic procedure is the reference method. Lesions will be confirmed as malignant by histopathologic examination. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. Tests were processed independently of colonoscopic findings. The test functions as a screening tool by generating a score, based on the detection of hemoglobin and multiple DNA methylation and mutational markers, together with an assessment of the total amount of human DNA in each sample. Specificity =100*(multi-target stool DNA test negative/negative colonoscopy)	Through study completion, an average of 60 days

Collaborators and Investigators

• Sponsor: Exact Sciences Corporation
• Investigators: Principal Investigator: Thomas Imperiale, MD, Indiana University

Publications and helpful links

General Publications

• Imperiale TF, Kisiel JB, Itzkowitz SH, Scheu B, Duimstra EK, Statz S, Berger BM, Limburg PJ. Specificity of the Multi-Target Stool DNA Test for Colorectal Cancer Screening in Average-Risk 45-49 Year-Olds: A Cross-Sectional Study. Cancer Prev Res (Phila). 2021 Apr;14(4):489-496. doi: 10.1158/1940-6207.CAPR-20-0294. Epub 2021 Jan 12.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Actual): June 18, 2019
• Study Completion (Actual): June 18, 2019

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): June 4, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Colonoscopy; Sample Collection; Stool DNA
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2018-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results reported in publications of the study will be shared after de-identification. This may include text, tables, figures, and appendices. The study protocol, statistical analysis plan, informed consent form, and clinical study report will also be shared. Data will be shared with researchers who provide a methodologically sound proposal to achieve the aims outlined in the approved proposal.
• IPD Sharing Time Frame: Data will be available from 2 years and ending 4 years after publication.
• IPD Sharing Access Criteria: Proposals for access to data should be directed to clinicaltrials@exactsciences.com. To gain access, data requestors will need to provide a methodologically sound proposal and sign a data access agreement. Researchers are required to obtain necessary IRB/EC approvals or waivers as applicable to conduct research.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No