Colorectal Cancer
Conditions
Keywords
Sample Collection, Stool DNA, Colonoscopy
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.
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.
Interventions
DIAGNOSTIC_TESTmt-sDNA screening test
Stool samples will be collected by the subject for the mt-sDNA screening test.
PROCEDUREColonoscopy
Subjects will undergo a screening colonoscopy.
Sponsors
Exact Sciences Corporation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
45 Years to 49 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specificity of the Multi-target Stool DNA Test in Average Risk Population, Ages 45-49 | Through study completion, an average of 60 days | 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) |
Countries
United States
Participant flow
Pre-assignment details
983 participants provided written informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Average Risk Patients Subjects were men and women 45-49 years of age, inclusive, who were at average risk of developing colorectal cancer. We compared results of a noninvasive, multi-target stool DNA test to colonoscopy. Histopathology was performed on any biopsy or excised lesions. | 842 |
| Total | 842 |
Baseline characteristics
| Characteristic | Average Risk Patients |
|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 1.5 |
| BMI: mean (SD) | 29.6 kg/m^2 STANDARD_DEVIATION 5.9 |
| Cigarette Smoking History n(%) Current Smoker | 86 Participants |
| Cigarette Smoking History n(%) Former Smoker | 174 Participants |
| Cigarette Smoking History n(%) Never Smoked | 582 Participants |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 48 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 794 Participants |
| Race/Ethnicity, Customized Race: American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race: Asian | 31 Participants |
| Race/Ethnicity, Customized Race: Black or African American | 95 Participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race: Other | 8 Participants |
| Race/Ethnicity, Customized Race: White | 706 Participants |
| Region of Enrollment United States | 842 participants |
| Sex: Female, Male Female | 402 Participants |
| Sex: Female, Male Male | 440 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 983 |
| other Total, other adverse events | 0 / 983 |
| serious Total, serious adverse events | 0 / 983 |
Outcome results
Primary
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)
Time frame: Through study completion, an average of 60 days
Population: All completed participants that had a negative colonoscopy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Multi-target DNA Test Results | Specificity of the Multi-target Stool DNA Test in Average Risk Population, Ages 45-49 | 95.3 percentage of participants |