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

• Sponsor: Exact Sciences Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03728348
• Collaborator: (none)
• Enrollment: 983
• Locations: 39
• Actual Duration (Months): 7.4
• Patients Per Site: 25.2
• Patients Per Site Per Month: 3.4

Study Details

Study Description

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	Phase
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.

Study Design

• 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: Nov 6, 2018
• Actual Primary Completion Date: Jun 18, 2019
• Actual Study Completion Date: Jun 18, 2019

Arms and Interventions

Arm	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 Names: Cologuard ; Procedure: Colonoscopy; Subjects will undergo a screening colonoscopy.

Outcome Measures

Primary Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85054
2	Ventura County Gastroenterology	Camarillo	California	United States	93012
3	Alliance Research Centers	Laguna Hills	California	United States	92653
4	Focilmed	Oxnard	California	United States	93030
5	Desert Oasis Healthcare Medical Group	Palm Springs	California	United States	92262
6	Gastroenterology Associates of Fairfield County	Bridgeport	Connecticut	United States	06606
7	Yale University Section of Digestive Diseases and Liver Diseases	New Haven	Connecticut	United States	06520
8	Precision Clinical Research, LLC	Lauderdale Lakes	Florida	United States	33319
9	Northshore University Health System Evanston Hospital	Evanston	Illinois	United States	60201
10	DM Clinical Research- Southwest Gastroenterology	Oak Lawn	Illinois	United States	60453
11	Deaconess Clinic- Mt. Pleasant	Evansville	Indiana	United States	47725
12	Indiana University, Eskanazi Hospital	Indianapolis	Indiana	United States	46202
13	Deaconess Clinic- Gateway	Newburgh	Indiana	United States	47630
14	Johnson County ClinTrials, LLC	Lenexa	Kansas	United States	66219
15	New Orleans Research Institute	Metairie	Louisiana	United States	70006
16	Delta Research Partners, LLC	Monroe	Louisiana	United States	71201
17	Louisiana Research Center	Shreveport	Louisiana	United States	71103
18	Investigative Clinical Research	Annapolis	Maryland	United States	21401
19	Centennial Medical Group	Elkridge	Maryland	United States	21075
20	Capitol Research	Rockville	Maryland	United States	20850
21	Commonwealth Clinical Studies	Brockton	Massachusetts	United States	02302
22	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
23	United Medical Associates	Binghamton	New York	United States	13901
24	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
25	Asheville Gastroenterology Associates	Asheville	North Carolina	United States	28801
26	Charlotte Gastroenterology & Hepatology, PLLC	Charlotte	North Carolina	United States	28207
27	Wilmington Gastroenterology Associates	Wilmington	North Carolina	United States	28403
28	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
29	Family Practice Center of Wooster, Inc./Clinical Trial Developers	Massillon	Ohio	United States	44647
30	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio	United States	44060
31	Comprehensive Internal Medicine, Inc.	Wooster	Ohio	United States	44691
32	Gastroenterology Associates, PA	Greenville	South Carolina	United States	29615
33	Gastro One	Germantown	Tennessee	United States	38138
34	Quality Medical Research, PLLC	Nashville	Tennessee	United States	37211
35	Austin Regional Clinic	Austin	Texas	United States	78726
36	University of Texas Health Science Center- McGovern Medical School	Houston	Texas	United States	77030
37	DM Clinical Research- PCP for Life	Houston	Texas	United States	77070
38	Virginia Gastroenterology Institute	Suffolk	Virginia	United States	23434
39	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Exact Sciences Corporation

Investigators

• Principal Investigator: Thomas Imperiale, MD, Indiana University

Study Documents (Full-Text)

• Study Protocol: Version 2 - Oct 16, 2018
• Study Protocol: Version 1 - Sep 21, 2018
• Statistical Analysis Plan - Jun 27, 2019

More Information

Publications

None provided.

• Responsible Party: Exact Sciences Corporation
• ClinicalTrials.gov Identifier: NCT03728348
• Other Study ID Numbers: 2018-10
• First Posted: Nov 2, 2018
• Last Update Posted: Jun 4, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: Colorectal Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	983 participants provided written informed consent.

Arm/Group Title	Average Risk Patients
Arm/Group Description	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, multitarget stool DNA test to colonoscopy. Histopathology was performed on any biopsy or excised lesions.
Period Title: Overall Study
STARTED	983
Did Not Complete Study Procedures	107
Multi-target DNA Test Excluded	15
Colonoscopy Excluded	19
COMPLETED	842
NOT COMPLETED	141

Baseline Characteristics

Arm/Group Title	Average Risk Patients
Arm/Group Description	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.
Overall Participants	842
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.9 (1.5)
Sex: Female, Male (Count of Participants)
Female	402 47.7%
Male	440 52.3%
Race/Ethnicity, Customized (Count of Participants)
Ethnicity: Hispanic or Latino	48 5.7%
Ethnicity: Not Hispanic or Latino	794 94.3%
Race: White	706 83.8%
Race: Black or African American	95 11.3%
Race: Asian	31 3.7%
Race: American Indian or Alaska Native	1 0.1%
Race: Native Hawaiian or Other Pacific Islander	1 0.1%
Race: Other	8 1%
Region of Enrollment (participants) [Number]
United States	842 100%
BMI: mean (SD) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.6 (5.9)
Cigarette Smoking History n(%) (Count of Participants)
Never Smoked	582 69.1%
Former Smoker	174 20.7%
Current Smoker	86 10.2%

Outcome Measures

1. Primary Outcome

Title	Specificity of the Multi-target Stool DNA Test in Average Risk Population, Ages 45-49
Description	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

Outcome Measure Data

Analysis Population Description

All completed participants that had a negative colonoscopy.

Arm/Group Title	Multi-target DNA Test Results
Arm/Group Description	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, multitarget stool DNA test to colonoscopy. Histopathology was performed on any biopsy or excised lesions.
Measure Participants	792
Number (95% Confidence Interval) [percentage of participants]	95.3 11.3%

Adverse Events

Time Frame	Through study completion, an average of 60 days
Adverse Event Reporting Description	Only device related adverse events were collected.
Arm/Group Title	Average Risk Patients
Arm/Group Description	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.
All Cause Mortality
	Average Risk Patients
	Affected / at Risk (%)	# Events
Total	0/983 (0%)
Serious Adverse Events
	Average Risk Patients
	Affected / at Risk (%)	# Events
Total	0/983 (0%)
Other (Not Including Serious) Adverse Events
	Average Risk Patients
	Affected / at Risk (%)	# Events
Total	0/983 (0%)

Limitations/Caveats

Subjects with colonoscopic non-advanced adenoma findings were included in the specificity analysis as disease status negative. The colonoscopically 'negative' population included subjects with no findings on colonoscopy and have a higher specificity.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal Investigator agreed that they shall not, without the Sponsor's prior written consent, independently publish, publicly disclose, present or discuss any results of or information pertaining to the activities conducted under their agreement for a period of one (1) year following completion of the Study.