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

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.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30300
      • Kaiser Permanente Georgia
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 49 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Eligible subjects will be identified at Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Georgia (KPGA). KPNW is a nonprofit group-model HMO with membership of about 485,000 in SW Washington and NW Oregon. KPNW includes 797 physician s and 395 allied clinicians (265 primary care providers). The member population base is similar to the local insured community in terms of age, gender, race, and ethnicity. About 19% of members are racial and ethnic minorities. Membership of KPGA has a racial and socioeconomic distribution similar to metropolitan Atlanta: ~ 50% Caucasian, 45% African American, 4% Hispanic, and 1% other races. 90 percent of the KPGA membership receives primary care at 12 medical offices owned and operated by KPGA and through contracts with 125 community practices.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Screening FIT positive; Patients aged 49-80, with a positive screening FIT, who are referred to colonoscopy, and who meet inclusion criteria.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Epigenomics, Inc
• Collaborators: Emory University; Kaiser Permanente
• Investigators: Principal Investigator: Gloria Coronado, PhD, Kaiser Permanente, Center for Health Research NW; Study Director: Amanda Petrik, Kaiser Permanente Center for Health Research NW

Study record dates

Study Major Dates

• Study Start: June 1, 2012

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: April 6, 2012
• First Posted (Estimate): April 10, 2012

Study Record Updates

• Last Update Posted (Estimate): August 4, 2014
• Last Update Submitted That Met QC Criteria: August 1, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Colorectal cancer; screening; fecal immunochemical test; Septin 9
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: Septin 9 Colorectal Biomarker