Colonic Diseases, Colorectal Cancer, Colorectal Neoplasms, Digestive System Diseases
Conditions
Keywords
Cancer, Colorectal Cancer, Neoplasm, Colorectal Neoplasm, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases
Brief summary
The primary objective is to determine the sensitivity and specificity of the Exact Colorectal Cancer (CRC) screening test for colorectal cancer, using colonoscopy as the reference method. Lesions will be confirmed as malignant by histopathologic examination. The secondary objective is to compare the performance of the Exact CRC screening test to a commercially available FIT assay, both with respect to cancer and advanced adenoma. Lesions will be confirmed as malignant or precancerous by colonoscopy and histopathologic examination.
Detailed description
Patients who are at average risk of developing colorectal cancer who are eligible for colorectal cancer screening will be asked to collect a single stool sample for the Exact CRC screening test and for the commercially available FIT assay. Subjects will undergo colonoscopy within 90 days of enrollment. Representative histopathology slides from tissue biopsied or excised during colonoscopy and representative histopathology slides resulting from subsequent definitive surgery may be retrieved in order to be evaluated by central pathology to confirm diagnosis and staging.
Interventions
None listed
Sponsors
Exact Sciences Corporation
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to 84 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subject is average risk for development of colorectal cancer (as defined by the inclusion and
Exclusion criteria
below). 2. Subject is able and willing to undergo a screening colonoscopy within 90 days of enrollment. 3. Subject is 50 to 84 years of age inclusive. 4. Subject is able to comprehend, sign, and date the written informed consent document to participate in the study. 5. Subject is able and willing to provide stool samples according to written instructions provided to them.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | 90 Days | An optical colonoscopic procedure is the reference method. Lesions will be confirmed as malignant by histopathologic examination. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and Beta-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were 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. Sensitivity= 100\*(multitarget DNA or FIT positive test/positive colonoscopy); Specificity= 100\*(multitarget DNA or FIT negative test/negative colonoscopy). |
Countries
Canada, United States
Participant flow
Pre-assignment details
12,776 participants provided written informed consent. 1,760 could not be evaluated (464- withdrew consent, 1,168- did not undergo colonoscopy, 128- did not submit stool sample).
Participants by arm
| Arm | Count |
|---|---|
| Average Risk Patients Subjects will be men and women, 50-84 years of age, inclusive, who are at average risk of developing colorectal cancer. We compared a noninvasive, multitarget stool DNA test with fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. Results were compared to colonoscopy and histopathology was performed on any biopsy or excised lesions. | 10,023 |
| Total | 10,023 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Colonoscopy excluded | 304 |
| Overall Study | FIT excluded | 34 |
| Overall Study | Multitarget DNA test excluded | 689 |
Baseline characteristics
| Characteristic | Average Risk Patients |
|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 8.42 |
| BMI | 28.83 kg/m^2 STANDARD_DEVIATION 5.836 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 991 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9028 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 36 Participants |
| Race (NIH/OMB) Asian | 259 Participants |
| Race (NIH/OMB) Black or African American | 1071 Participants |
| Race (NIH/OMB) More than one race | 206 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 23 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 8422 Participants |
| Sex: Female, Male Female | 5378 Participants |
| Sex: Female, Male Male | 4645 Participants |
| Smoking History Current Smoker | 903 participants |
| Smoking History Former Smoker | 3589 participants |
| Smoking History Never Smoked | 5531 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 11,016 |
| serious Total, serious adverse events | 0 / 11,016 |
Outcome results
Primary
Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer.
An optical colonoscopic procedure is the reference method. Lesions will be confirmed as malignant by histopathologic examination. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and Beta-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were 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. Sensitivity= 100\*(multitarget DNA or FIT positive test/positive colonoscopy); Specificity= 100\*(multitarget DNA or FIT negative test/negative colonoscopy).
Time frame: 90 Days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity CRC and HGD | 83.7 percent |
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity nonadvanced adenoma | 17.2 percent |
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity Stage I to III | 93.3 percent |
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Specificity nonsignificant findings | 86.6 percent |
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity Advanced precancerous lesions | 42.2 percent |
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Specificity negative results colonoscopy | 89.8 percent |
| Multitarget DNA Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity for any Colorectal Cancer | 92.3 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Specificity negative results colonoscopy | 96.4 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity for any Colorectal Cancer | 73.8 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity Stage I to III | 73.3 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity CRC and HGD | 63.5 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity Advanced precancerous lesions | 23.8 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Sensitivity nonadvanced adenoma | 7.6 percent |
| FIT Test Results | Sensitivity and Specificity of the Exact CRC Screening Test With Comparison to Colonoscopy, Both With Respect to Cancer. | Specificity nonsignificant findings | 94.9 percent |