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

Gloria Coronado, PhD

Amanda Petrik

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.

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

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.

Patient demographic factor such as age and gender will be assessed.

Co-morbid conditions will include, for example, diabetes, congestive heart failure, etc.

Medications will include common medications in screening population (ie. blood thinners).

Kaiser Permanente

Emory University

Epigenomics, Inc

Patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Patients who call will speak to a research assistant who is trained in patient navigation and can facilitate referrals for colonoscopy or FIT. Patients will receive a follow-up telephone call that reiterates information in the letter.

Patients will also be asked to complete a questionnaire about their beliefs and attitudes regarding CRC screening. The questionnaire will be mailed with the invitation letter and will also be administered over the telephone by the research assistant.

Patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Letters will also include an option to participate in the blood test, with instructions to call the study number to schedule the blood draw. This option will not appear in the letters sent to the control group. Patients will also receive a follow-up telephone call and a questionnaire.

Participants who choose to the blood test (Septin9) will undergo phlebotomy. The blood sample will be run by an off-site commercial laboratory. The study team will notify patients and their primary care physicians of blood test results and will facilitate a colonoscopy referral for those with positive tests.

Septin9 is a FDA-approved blood test for colorectal cancer screening

Septin9

Objectives:

Colonoscopy and stool-based testing are the two predominant colorectal cancer (CRC) screening tests used in the US, and both reduce colorectal cancer mortality. However, only 62% of Americans are up to date with screening, partly because many individuals find these two tests inconvenient or unacceptable for a variety of reasons. There is an unmet need for a non-invasive test that does not require bowel preparation or handling stool, and the Septin9 DNA blood test may be an alternative for those individuals who would otherwise remain unscreened.

Aims:

Aim 1: To measure screening uptake with a blood test in screen-resistant patients who have declined both colonoscopy and fecal immunochemical testing (FIT) at the Manhattan VA Medical Center

* Sub-Aim 1a: To assess the proportion of those with a positive blood-based screening test who undergo diagnostic colonoscopy
* Sub-Aim 1b: To describe the endoscopic findings on diagnostic colonoscopy

Aim 2: To survey screen-resistant patients to understand their beliefs and attitudes about colorectal cancer screening and testing options

We hypothesize that a substantial proportion of patients who have refused colonoscopy and FIT will accept the blood test. We hypothesize this will be driven by the convenience of the blood test.

Methods:

This will be randomized controlled trial of individuals who have refused colonoscopy and FIT within past 6 months. Eligible patients will be randomized 1:1 to the intervention or control group. Both groups will be invited to participate in navigated colonoscopy or FIT by letter and telephone call. The intervention group will also be invited to participate in the blood test if they refuse colonoscopy and FIT. We will enroll 180 participants in each group (total n=360).

The proposed study is a randomized controlled trial that will 1) assess the uptake of a CRC screening blood test among patients who have declined both colonoscopy and FIT in the previous 6 months, including diagnostic evaluation of positive results and 2) survey patients about their beliefs and attitudes regarding CRC screening and testing options. All participants will be primary care patients at the Manhattan VA Medical Center. Based on a recent internal audit, there were 1502 patients who had at least one primary care visit from August 2016 through August 2017 and were not up to date with CRC screening. Up-to-date CRC screening is defined as either 1) a colonoscopy within the past 10 years or 2) FIT within the past year. We will perform an updated CRC screening audit at the beginning of the study to obtain the entire pool of eligible patients who are not up to date with screening. Eligible patients will then be randomized 1:1 to either an intervention group or a control group. All patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Patients who call will speak to a research assistant who is trained in patient navigation and can facilitate referrals for colonoscopy or FIT. Following the sequential testing approach, letters addressed to the intervention group will also include an option to participate in the blood test, with instructions to call the study number to schedule the blood draw. In addition to the letter, both groups will also receive a follow-up telephone call that reiterates information in the letter. The research assistant will make and receive all calls using a standard script. All patients will also be asked to complete a survey about their beliefs and attitudes regarding CRC screening. The survey will be mailed with the invitation letter and will also be administered over the telephone by the research assistant. The study team will notify patients and their primary care physicians of blood test results and will facilitate a colonoscopy referral for those with positive tests. Primary care physicians will not be asked to notify the patients or make the colonoscopy referral because most will not have adequate knowledge of the Septin9 test to provide appropriate patient education.

Participants who are randomized to the blood test arm will undergo phlebotomy, which will be performed by the study research assistant. The blood sample will be temporarily stored on-site and then transported to an off-site commercial laboratory (Lenco Diagnostic Laboratory, Brooklyn, NY) to run the assay.

Clinical outcomes for both the intervention and control group participants will be measured as a secondary outcome. This includes timing and result of a screening colonoscopy or FIT for individuals in the controls group as well as diagnostic colonoscopy for participants who had a positive blood test.

Eligible patients will be randomized 1:1 to the intervention or control group

Assessing the Effect of a Blood-based Colorectal Cancer Screening Test on Screening Adherence and Colonoscopy Completion

Assessing the Effect of Offering a Blood-based Colorectal Cancer Screening Test on Screening Adherence and Colonoscopy Completion in Patients Who Have Refused Colonoscopy and FIT

Percentage of participants who undergo screening in the intervention group vs. control group, measured 6 months after the initial letter was sent

Complete screening in both groups, which is defined as completion of the entire screening strategy. For colonoscopy, this requires cecal intubation and an adequate bowel preparation. For individuals who took Septin9 and FIT, positive results must be followed by a colonoscopy with cecal intubation and adequate bowel preparation.

Among individuals in the intervention group who had a positive blood test, proportion who completed a follow-up colonoscopy within 6 months.

Percentage of both groups who answered that they would be willing to take a blood test for colorectal cancer screening

The most commonly cited advantages of a blood test compared to colonoscopy and stool test in both groups

The most commonly cited reasons for not taking the blood test in the intervention group.

Peter S. Liang, MD MPH

Staff Physician

Control

Patients will receive a letter noting that they are not up-to-date on screening and encouraging them to contact a study number if they choose to screen with colonoscopy or FIT. Letters will also include an option to participate in the blood test, with instructions to call the study number to schedule the blood draw. This option will not appear in the letters sent to the control group. Patients will also receive a follow-up telephone call and a questionnaire.

Participants who choose to the blood test (Septin9) will undergo phlebotomy. The blood sample will be run by an off-site commercial laboratory. The study team will notify patients and their primary care physicians of blood test results and will facilitate a colonoscopy referral for those with positive tests.

Septin9: Septin9 is a FDA-approved blood test for colorectal cancer screening

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

The analysis population is excluding Hispanics in this total, as it was already recorded in a different section. This is why the total is less than the original total.

Race (NIH/OMB)

United States

Region of Enrollment

Individuals who are eligible for colorectal cancer screening and have previously declined colonoscopy and FIT.

Anika Zaman

Percentage of Participants Who Undergo Screening Within 6 Months of Outreach

Percentage of Participants Completing Screening Strategy

The overall number of participants analyzed corresponds to the number of participants with a positive FIT.

Percentage of Participants With Colonoscopy Follow-up in Intervention Group

The survey was sent out to both control and intervention patients and all surveys contained the same questions. It investigated patients' perspectives on colonoscopy and FIT in order to understand barriers to screening. The survey also assessed whether these patients would be amenable to a blood-based CRC screening test.

Surveys/Questionnaires Mailed

The same survey was sent to all participants. The planned analysis was to include all participants who returned the survey, rather than stratified by arm.

Self-reported Willingness to Take Blood Test for Colorectal Cancer Screening on Questionnaire

Patients are willing to go through a blood test for colorectal cancer screening due to the convenience of taking a blood test.

Convenience

Patients are willing to take blood tests for colorectal cancer screening due to a lack of extra preparation for a blood test.

No Special Preperation

Patients are willing to do a blood test for colorectal cancer screening because they feel accustomed to blood draw tests.

Accustomed to Blood Tests

Self-reported Most Common Advantages of Blood Test on Questionnaire

Patients who declined blood draws for colorectal cancer do not believe it is as accurate as the FIT test.

Not as Accurate as FIT

Patients who declined blood draws for colorectal cancer screening state they are uncomfortable with blood draws.

Uncomfortable With Blood Draws

The overall number of participants who indicated that they would refuse a blood test on the questionnaire.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Assessment of Septin9 Biomarker for Detection of Colorectal Cancer in Patients With Positive Fecal Immunochemical Test	NCT01574677	Colorectal Canc...		49 Years - 80 Years	Epigenomics, Inc
Assessing the Effect of a Blood-based Colorectal Cancer Screening Test on Screening Adherence and Colonoscopy Completion	NCT03598166	Colorectal Canc...	Septin9	50 Years - 75 Years	VA New York Harbor Healthcare System

Spots Global Cancer Trial Database for septin 9

Every month we try and update this database with for septin 9 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for septin 9

Every month we try and update this database with for septin 9 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for septin 9 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.