Assessment of Septin9 Biomarker for Detection of Colorectal Cancer in Patients With Positive Fecal Immunochemical Test

Study Overview
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Brief Summary
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Colorectal cancer (CRC) is the second leading cause of cancer death in the United States and affects men and women almost equally. The United States Preventative Services Task Force (USPSTF) currently recommends screening with any of three options, which include fecal testing, flexible sigmoidoscopy, or colonoscopy. Screening for CRC with fecal occult blood testing (using a guaiac-based test) done annually or biennially has been shown to decrease mortality 15-33% primarily through detection of early stage cancer. Guaiac fecal occult blood testing (gFOBT) has a known positive balance of benefit and risk in screening populations, is the least expensive, and is the preferred method of screening in 30-55% of patients. The fecal immunochemical test (FIT) offers significant improvements over the gFOBT, most notably that it is easier to use (requires fewer samples and no dietary or medication restrictions) and is more sensitive than the gFOBT with respect to detecting both CRC and precancerous adenomas. As a result of improved test performance and usability, in 2008 multiple professional societies endorsed the use of four types of FITs for colorectal cancer screening. Kaiser Permanente currently uses the OC-Micro FIT as the fecal screening test in all regions. In recent years, intensive efforts have been undertaken to identify blood-based markers that may provide a promising alternative or supplement to fecal testing for non-invasive CRC screening. One method under development is to identify aberrantly methylated genes in cancer tissue through a blood test. Prior studies have explored those specific colorectal cancer genes that show the highest differences in methylation between the cancer and background genetic expression. Of these, methylation of the Septin 9 gene through a qPCR assay is relatively well studied. The proposed study aims to evaluate whether the Septin 9 biomarker may be used to supplement the OC-Micro FIT for colorectal cancer screening in such a way as to safely reduce unneeded colonoscopies. The population of interest for this study-those with a positive screening OC-Micro fecal immunochemical test-has a CRC prevalence of approximately 5%. Knowing how well Septin 9 can identify those without cancer prior to colonoscopy is important largely because colonoscopy, even when done diagnostically (e.g., after a positive FIT result), can cause serious complications.

Official Title
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Assessment of Septin9 Biomarker for Detection of Colorectal Cancer in Patients With Positive Fecal Immunochemical Test

Conditions
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Colorectal Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 49-80 Member of Kaiser Permanente Northwest or Southeast English or Spanish speaking Had a positive fecal screening (FIT) and has an active referral to colonoscopy Exclusion Criteria: Having a personal history of colon cancer Having had a prior colonoscopy within 5 years Currently under hospice care Currently in a skilled nursing facility Currently being treated for active cancer (any type) Having ever had carcinoid tumor or full colectomy Having indicated a preference at enrollment into Kaiser health plan to not participate in research

Ages Eligible for Study
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Minimum Age: 49 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Screening FIT positive<br>Patients aged 49-80, with a positive screening FIT, who are referred to colonoscopy, and who meet inclusion criteria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance characteristics of the Septin 9 biomarker among patients who have a positive FIT result | Sensitivity, specificity, positive predictive value, and negative predictive value of Septin 9 (relative to colonoscopy) for detecting CRC in a sample of individuals with a positive test result for single-sample OC-Micro FIT using various thresholds for Septin 9 positivity. | Participants are prospectively enrolled. Eligible participants will be asked to provide a blood sample at least 2 days prior to receiving a colonoscopy. The timeframe for participation will generally be within 3 months of receiving a positive FIT result. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance and discordance (Kappa scores) between Septin 9 test results and colonoscopy findings associated with patient demographic factors. | Patient demographic factor such as age and gender will be assessed. | The timeframe for participation will generally be within 3 months of receiving a positive FIT result. | 
| Concordance and discordance (Kappa scores) between Septin 9 test results and colonoscopy findings associated with co-morbid conditions. | Co-morbid conditions will include, for example, diabetes, congestive heart failure, etc. | The timeframe for participation will generally be within 3 months of receiving a positive FIT result. | 
| Concordance and discordance (Kappa scores) between Septin 9 test results and colonoscopy findings associated with specific medication use practices. | Medications will include common medications in screening population (ie. blood thinners). | The timeframe for participation will generally be within 3 months of receiving a positive FIT result. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, fecal immunochemical test, Septin 9, screening