Screening With a DNA Blood Test to Address Colorectal Cancer Inequities

NCT ID: NCT06929481

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-28
• Study Completion Date: 2026-05-31

Brief Summary

Colorectal cancer (CRC) screening participation is suboptimal and associated with inequities in CRC outcomes by race/ethnicity and socioeconomic position. A novel, cell free DNA (cfDNA) blood test has potential to increase participation, but has not been studied in groups at highest risk for adverse CRC outcomes. Among patients age-eligible for colorectal cancer screening, not up-to-date, we propose a 2-arm, pragmatic, randomized controlled trial comparing offers of standard screening options (at home fecal immunochemical test (FIT) or colonoscopy) vs. offers of expanded options (at home FIT, colonoscopy, or in clinic cfDNA plus at home FIT), set at a large Federally Qualified Health Center serving individuals at increased risk for inequities in CRC outcomes. Results will inform guideline and policy makers on whether cfDNA should be supported as a screening option, and support planning for a large-scale trial examining impact of a cfDNA option for screening on CRC and advanced neoplasia detection.

Detailed Description

Patients assigned to usual care will be offered options for screening using a standardized script outlining: 1) importance of screening; 2) option of screening with at home FIT or colonoscopy, including key characteristics. Description of key characteristics will include 1) test completion steps; 2) test performance, stating that colonoscopy picks up 9 out of 10 colorectal cancers and important growths called polyps, and that FIT picks up 3 in 4 cancers and 1 in 4 important polyps (we define "important polyps" as adenomas 1 centimeter or larger in size or containing villous/tubulovillous histology or high-grade dysplasia). The script will note abnormal FIT requires a colonoscopy to check for CRC and important growths. Patients assigned to the intervention group will receive an identical offer, but with additional option of screening with an in clinic cfDNA plus an at home FIT. The script will state cfDNA is a blood test meant to be complementary to current screening with ability to detect 8 out of 10 CRCs and 1 in 10 important polyps, and offers advantage of having a same day test for CRC detection to complement the FIT that they will do at home. The script will also state colonoscopy is required if either cfDNA or FIT is abnormal. For patients who opt for the cfDNA plus at home FIT option, the study team will coordinate same day blood draw. Following manufacturer's instructions, 40 mL of blood (4 tubes each with 10 mL of blood) will be collected and sent to Guardant Health for the Guardant Shield test. Patients will be instructed to complete the FIT as soon as possible and within 5 days, and, to minimize the influence of cfDNA result on likelihood of FIT completion, cfDNA results will not be disclosed to the patient for 14 days after the clinic visit. For all subjects, demographic characteristics, coded data on primary provider of record, and outcomes will be collected. Because this is planned as a pragmatic trial to mimic the potential impact of introducing the cfDNA test into usual care, and because the study poses minimum risk and promotes potentially lifesaving colorectal cancer screening, a waiver of informed consent for study screening and randomization to study group assignment, and for written documentation of informed consent has been approved. An informed consent sheet with the option to "opt out" of the study will be provided to all potential subjects.

Conditions

Colorectal Cancer Screening; Colorectal Cancer (CRC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: SINGLE

Study Groups

Intervention Group

Participants randomized to the intervention group will be offered expanded colorectal cancer screening options: at home FIT, colonoscopy, or additional option of an in clinic FDA-approved cfDNA blood test with at home FIT.

Group Type: EXPERIMENTAL

Cell free DNA (cfDNA) blood test

Intervention Type: DEVICE

The intervention is a novel blood test that evaluates circulating cell free tumor DNA (cfDNA) and detects colorectal cancer (CRC). Recently, the cfDNA test has been shown to have 83% sensitivity and 90% specificity for CRC detection, and 13% sensitivity for advanced polyp detection, heralding a new screening strategy postulated to be highly convenient and acceptable. The cfDNA test is made by Guardant Health, FDA approved for average risk colorectal cancer screening, and marketed with the brand name "Shield". Patients opting for the cfDNA test will also be requested to complete an at home FIT.

At home Fecal Immunochemical Test (FIT) or Colonoscopy

Intervention Type: OTHER

The usual care group will be offered standard colorectal cancer screening options to choose from: at home FIT or colonoscopy.

Usual Care Group

Participants randomized to the usual care group will be offered standard colorectal cancer screening options: at home FIT or colonoscopy.

Group Type: ACTIVE_COMPARATOR

At home Fecal Immunochemical Test (FIT) or Colonoscopy

Intervention Type: OTHER

The usual care group will be offered standard colorectal cancer screening options to choose from: at home FIT or colonoscopy.

Interventions

Cell free DNA (cfDNA) blood test

The intervention is a novel blood test that evaluates circulating cell free tumor DNA (cfDNA) and detects colorectal cancer (CRC). Recently, the cfDNA test has been shown to have 83% sensitivity and 90% specificity for CRC detection, and 13% sensitivity for advanced polyp detection, heralding a new screening strategy postulated to be highly convenient and acceptable. The cfDNA test is made by Guardant Health, FDA approved for average risk colorectal cancer screening, and marketed with the brand name "Shield". Patients opting for the cfDNA test will also be requested to complete an at home FIT.

Intervention Type: DEVICE

At home Fecal Immunochemical Test (FIT) or Colonoscopy

The usual care group will be offered standard colorectal cancer screening options to choose from: at home FIT or colonoscopy.

Intervention Type: OTHER

Other Intervention Names

cfDNA; cfDNA blood test; Guardant Shield cfDNA test; Guardant Shield test; at home FIT or colonoscopy

Eligibility Criteria

Inclusion Criteria

1. Persons, aged 45 to 75 years old

2. Not up-to-date with screening, defined based on an existing electronic health record (EHR)-based flag that indicates absence of FIT within the last 12 months, colonoscopy within the last 10 years, sigmoidoscopy within the last 5 years or multi-target stool DNA (Cologuard) test within 3 years.

3. Attending primary care visits during the 2 months of recruitment. According to routine practice, screening status will be confirmed by primary care providers as part of routine visits.

4. Being provided the informed consent form.

Exclusion Criteria

1. Personal history of colorectal cancer (CRC), adenomas, or other related cancers.

2. Prior history of colorectal surgery

3. Family history of CRC, defined as having one or more first-degree relative (parent, sibling, or child) diagnosed with CRC at any age.

4. Up-to-date with colorectal cancer screening, defined as:

• Fecal occult blood test (FOBT) or FIT within the last 12 months
• FIT-DNA (Cologuard) or FIT-RNA (Colosense) test within 3 years
• cfDNA (Shield) within the last year
• CT colonography within the last 5 years
• Sigmoidoscopy within the last 5 years
• Colonoscopy within the last 10 years

5. Abnormal FIT, FOBT, cfDNA, FIT-DNA, or FIT-RNA test within the last 3 years.

6. Personal history of any of the following high-risk conditions for colorectal cancer:

• Inflammatory Bowel Disease (IBD), including chronic ulcerative colitis (CUC) and Crohn's disease
• Familial adenomatous polyposis (FAP)
• Other hereditary cancer syndromes including but not limited to:

• Hereditary non-polyposis colorectal cancer syndrome (HNPCC) or "Lynch Syndrome", Peutz-Jeghers Syndrome, MUTYH Polyposis (MAP), Familial Adenomatous Polyposis (FAP), Cowden's Syndrome, Juvenile Polyposis, Serrated Polyposis Syndrome

7. Uninsured patients will be excluded because of inability to ensure follow up. Because of recently expanded Medi-Cal eligibility, exclusions due to insurance are expected to be minimal.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CUREBOUND, INC.

UNKNOWN

Sponsor Role: collaborator

Family Health Centers of San Diego

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Samir Gupta

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Samir Gupta, MD, MSCS, AGAF

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Job G Godino, PhD

Role: PRINCIPAL_INVESTIGATOR

Family Health Centers of San Diego

Locations

Family Health Centers of San Diego, Logan Heights site

San Diego, California, United States

Countries

United States

References

Gupta S, Halm EA, Rockey DC, Hammons M, Koch M, Carter E, Valdez L, Tong L, Ahn C, Kashner M, Argenbright K, Tiro J, Geng Z, Pruitt S, Skinner CS. Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med. 2013 Oct 14;173(18):1725-32. doi: 10.1001/jamainternmed.2013.9294.

Reference Type: BACKGROUND

PMID: 23921906 (View on PubMed)

Singal AG, Gupta S, Tiro JA, Skinner CS, McCallister K, Sanders JM, Bishop WP, Agrawal D, Mayorga CA, Ahn C, Loewen AC, Santini NO, Halm EA. Outreach invitations for FIT and colonoscopy improve colorectal cancer screening rates: A randomized controlled trial in a safety-net health system. Cancer. 2016 Feb 1;122(3):456-63. doi: 10.1002/cncr.29770. Epub 2015 Nov 4.

Reference Type: BACKGROUND

PMID: 26535565 (View on PubMed)

Gupta S, Miller S, Koch M, Berry E, Anderson P, Pruitt SL, Borton E, Hughes AE, Carter E, Hernandez S, Pozos H, Halm EA, Gneezy A, Lieberman AJ, Sugg Skinner C, Argenbright K, Balasubramanian B. Financial Incentives for Promoting Colorectal Cancer Screening: A Randomized, Comparative Effectiveness Trial. Am J Gastroenterol. 2016 Nov;111(11):1630-1636. doi: 10.1038/ajg.2016.286. Epub 2016 Aug 2.

Reference Type: BACKGROUND

PMID: 27481306 (View on PubMed)

Singal AG, Gupta S, Skinner CS, Ahn C, Santini NO, Agrawal D, Mayorga CA, Murphy C, Tiro JA, McCallister K, Sanders JM, Bishop WP, Loewen AC, Halm EA. Effect of Colonoscopy Outreach vs Fecal Immunochemical Test Outreach on Colorectal Cancer Screening Completion: A Randomized Clinical Trial. JAMA. 2017 Sep 5;318(9):806-815. doi: 10.1001/jama.2017.11389.

Reference Type: BACKGROUND

PMID: 28873161 (View on PubMed)

Lieberman A, Gneezy A, Berry E, Miller S, Koch M, Ahn C, Balasubramanian BA, Argenbright KE, Gupta S. Financial Incentives to Promote Colorectal Cancer Screening: A Longitudinal Randomized Control Trial. Cancer Epidemiol Biomarkers Prev. 2019 Nov;28(11):1902-1908. doi: 10.1158/1055-9965.EPI-19-0039. Epub 2019 Aug 6.

Reference Type: BACKGROUND

PMID: 31387970 (View on PubMed)

Lieberman A, Gneezy A, Berry E, Miller S, Koch M, Argenbright KE, Gupta S. The effect of deadlines on cancer screening completion: a randomized controlled trial. Sci Rep. 2021 Jul 6;11(1):13876. doi: 10.1038/s41598-021-93334-1.

Reference Type: BACKGROUND

PMID: 34230556 (View on PubMed)

Castaneda SF, Gupta S, Nodora JN, Largaespada V, Roesch SC, Rabin BA, Covin J, Ortwine K, Preciado-Hidalgo Y, Howard N, Halpern MT, Martinez ME. Hub-and-Spoke centralized intervention to optimize colorectal cancer screening and follow-up: A pragmatic, cluster-randomized controlled trial protocol. Contemp Clin Trials. 2023 Nov;134:107353. doi: 10.1016/j.cct.2023.107353. Epub 2023 Oct 5.

Reference Type: BACKGROUND

PMID: 37802222 (View on PubMed)

Arredondo EM, Dumbauld J, Milla M, Madanat H, Coronado GD, Haughton J, Garcia-Bigley F, Ramers C, Nodora J, Bharti B, Lopez G, Diaz M, Marquez J, Gupta S. A Promotor-Led Pilot Study to Increase Colorectal Cancer Screening in Latinos: The Juntos Contra El Cancer Program. Health Promot Pract. 2021 Jul;22(4):491-501. doi: 10.1177/1524839920912240. Epub 2020 Mar 22.

Reference Type: BACKGROUND

PMID: 32202155 (View on PubMed)

De La Torre CL, Dumbauld JN, Haughton J, Gupta S, Nodora J, Giacinto RE, Ramers C, Bharti B, Wells K, Lopez J, Diaz M, Moody J, Arredondo EM. Development of a Group-Based Community Health Worker Intervention to Increase Colorectal Cancer Screening Among Latinos. Hisp Health Care Int. 2021 Mar;19(1):47-54. doi: 10.1177/1540415320923564. Epub 2020 May 29.

Reference Type: BACKGROUND

PMID: 32466687 (View on PubMed)

Castaneda SF, Bharti B, Rojas M, Mercado S, Bearse AM, Camacho J, Lopez MS, Munoz F, O'Connell S, Liu L, Talavera GA, Gupta S. Outreach and Inreach Strategies for Colorectal Cancer Screening Among Latinos at a Federally Qualified Health Center: A Randomized Controlled Trial, 2015-2018. Am J Public Health. 2020 Apr;110(4):587-594. doi: 10.2105/AJPH.2019.305524. Epub 2020 Feb 20.

Reference Type: BACKGROUND

PMID: 32078353 (View on PubMed)

Bharti B, May FFP, Nodora J, Martinez ME, Moyano K, Davis SL, Ramers CB, Garcia-Bigley F, O'Connell S, Ronan K, Barajas M, Gordon S, Diaz G, Ceja E, Powers M, Arredondo EM, Gupta S. Diagnostic colonoscopy completion after abnormal fecal immunochemical testing and quality of tests used at 8 Federally Qualified Health Centers in Southern California: Opportunities for improving screening outcomes. Cancer. 2019 Dec 1;125(23):4203-4209. doi: 10.1002/cncr.32440. Epub 2019 Sep 3.

Reference Type: BACKGROUND

PMID: 31479529 (View on PubMed)

Mohl JT, Ciemins EL, Miller-Wilson LA, Gillen A, Luo R, Colangelo F. Rates of Follow-up Colonoscopy After a Positive Stool-Based Screening Test Result for Colorectal Cancer Among Health Care Organizations in the US, 2017-2020. JAMA Netw Open. 2023 Jan 3;6(1):e2251384. doi: 10.1001/jamanetworkopen.2022.51384.

Reference Type: BACKGROUND

PMID: 36652246 (View on PubMed)

Ciemins EL, Mohl JT, Moreno CA, Colangelo F, Smith RA, Barton M. Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e242693. doi: 10.1001/jamanetworkopen.2024.2693.

Reference Type: BACKGROUND

PMID: 38526494 (View on PubMed)

Shareef F, Bharti B, Garcia-Bigley F, Hernandez M, Nodora J, Liu J, Ramers C, Nery JD, Marquez J, Moyano K, Rojas S, Arredondo E, Gupta S. Abnormal Colorectal Cancer Test Follow-Up: A Quality Improvement Initiative at a Federally Qualified Health Center. J Prim Care Community Health. 2024 Jan-Dec;15:21501319241242571. doi: 10.1177/21501319241242571.

Reference Type: BACKGROUND

PMID: 38554066 (View on PubMed)

Ladabaum U, Mannalithara A, Weng Y, Schoen RE, Dominitz JA, Desai M, Lieberman D. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391. doi: 10.1053/j.gastro.2024.03.011. Epub 2024 Mar 26.

Reference Type: BACKGROUND

PMID: 38552670 (View on PubMed)

Lieberman DA; AGA CRC Workshop Panel. Commentary: Liquid Biopsy for Average-Risk Colorectal Cancer Screening. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1160-1164.e1. doi: 10.1016/j.cgh.2024.01.034. Epub 2024 Mar 26. No abstract available.

Reference Type: BACKGROUND

PMID: 38552672 (View on PubMed)

Coronado GD, Jenkins CL, Shuster E, Johnson C, Amy D, Cook J, Sahnow S, Zepp JM, Mummadi R. Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence. Gut. 2024 Mar 7;73(4):622-628. doi: 10.1136/gutjnl-2023-330980.

Reference Type: BACKGROUND

PMID: 38176899 (View on PubMed)

Chung DC, Gray DM 2nd, Singh H, Issaka RB, Raymond VM, Eagle C, Hu S, Chudova DI, Talasaz A, Greenson JK, Sinicrope FA, Gupta S, Grady WM. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983. doi: 10.1056/NEJMoa2304714.

Reference Type: BACKGROUND

PMID: 38477985 (View on PubMed)

Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023 May-Jun;73(3):233-254. doi: 10.3322/caac.21772. Epub 2023 Mar 1.

Reference Type: BACKGROUND

PMID: 36856579 (View on PubMed)

Other Identifiers

316051-00001

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

811489

Identifier Type: -

Identifier Source: org_study_id