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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 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.
 
ClinicalTrials.gov Identifier: NCT03728348
Recruitment Status : Completed
First Posted : November 2, 2018
Last Update Posted : February 7, 2020
Sponsor:
Information provided by (Responsible Party):
Exact Sciences Corporation

Brief Summary:
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.

Condition or disease Intervention/treatment
Colorectal Cancer Diagnostic Test: mt-sDNA screening test Procedure: Colonoscopy

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.

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Study Type : Observational
Actual Enrollment : 983 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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
Actual Study Start Date : November 6, 2018
Actual Primary Completion Date : June 18, 2019
Actual Study Completion Date : June 18, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Subject aged 45-49 with Average CRC Risk
Subject aged 45-49 with average risk for development of CRC.
Diagnostic Test: mt-sDNA screening test
Stool samples will be collected by the subject for the mt-sDNA screening test.
Other Name: Cologuard

Procedure: Colonoscopy
Subjects will undergo a screening colonoscopy.




Primary Outcome Measures :
  1. Specificity of mt-sDNA Test [ Time Frame: Study Duration: Through study completion, an average of 180 days. ]
    The primary endpoint of this study is specificity of the mt-sDNA test (Cologuard) in the 45-49 age group in an average risk population, using colonoscopy with histopathology (when required) as the reference method. The primary analysis requires the one-sided 97.5% lower bound of the specificity of Cologuard to exceed 85.0%.


Other Outcome Measures:
  1. Sensitivity for CRC + advanced adenoma [ Time Frame: Through study completion, an average of 180 days. ]
    The sensitivity (Se) or true positive fraction of the test is defined as TP/(TP + FN)

  2. The positive and negative predictive values [ Time Frame: Through study completion, an average of 180 days. ]
    The Positive Predictive Value (PPV) is defined as: TP/(TP+FP) and/or (Se*Prevalence)/[Se*Prevalence+(1-Sp)*(1-Prevalence)]. The Negative Predictive Value (NPV) is defined as: TN/(FN+TN) and/or [Sp*(1-Prevalence)]/[(1-Se)*(Prevalence+Sp*(1-Prevalence)].

  3. The positive and negative likelihood ratios (PLR and NLR, respectively) [ Time Frame: Through study completion, an average of 180 days. ]
    The positive likelihood ratio (PLR) is defined as Se/(1-Sp). The negative likelihood ratio (NLR) is defined as (1-Se)/(Sp).

  4. The distribution of colorectal epithelial lesions (by Category) among positive mt-sDNA test (Cologuard) subjects [ Time Frame: Through study completion, an average of 180 days. ]
    The distribution between Advanced Neoplasia (AN) Colonoscopic findings that include colorectal cancer (CRC) and advanced adenoma (AA) and Non-advanced neoplasia (NAN) - Colonoscopic findings ≤ 1.0 cm that exclude colorectal cancer (CRC) and advanced adenoma (AA) and absent any colonoscopy findings.

  5. The rate of no mt-sDNA (Cologuard) result [ Time Frame: Through study completion, an average of 180 days. ]
    Observed percent of attempted tests that do not produce a positive or negative result. (Percent analytical test failure.)


Biospecimen Retention:   Samples With DNA
Residual stool samples may be used to develop and evaluate the performance of biomarker assays to detect cancers. Sample may be stored for up to 20 years. These stool samples will be de-identified.


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:   45 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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.

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 ClinicalTrials.gov identifier (NCT number): NCT03728348


Locations
Show Show 39 study locations
Sponsors and Collaborators
Exact Sciences Corporation
Investigators
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Principal Investigator: Thomas Imperiale, MD Indiana University

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Responsible Party: Exact Sciences Corporation
ClinicalTrials.gov Identifier: NCT03728348    
Other Study ID Numbers: 2018-10
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data will be available from 2 years and ending 4 years after publication.
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.

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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
Keywords provided by Exact Sciences Corporation:
Sample Collection
Stool DNA
Colonoscopy
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases