Colorectal CancerAACRCNCT06342440
Early Detection of Advanced Adenomas and Colorectal Cancer
An observational study of Colorectal Cancer and Colorectal Neoplasms, run by City of Hope Medical Center at 6 sites in 5 countries.
Trial summary
This study aims to develop a highly sensitive, specific, and cost-effective blood assay for early detection of colorectal adenomas and cancer, using advanced machine learning and state-of-the-art biological analyses. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer, Colorectal Neoplasms, Colorectal Polyp
- What is being tested?
- DENEB
- How many people
- 2,000 participants
- Where
- 6 sitesin 5 countries
- Study dates
- 15 Mar 2020to 18 Jun 2028
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Three independent cohorts of individuals who belong to one of the following four * Negative colonoscopy findings * Low-risk adenomas (at most) * Advanced adenomas (at most) * Colorectal cancer
Who may be able to join
- All individuals included in the study need to have had a colonoscopy at the time of blood sampling.
- Received standard diagnostic and staging (as necessary) procedures as per local guidelines, and at least one sample was drawn before receiving any curative-intent treatment.
- Received standard pathological and endoscopic diagnosis and assessment for cohort assignment.
Who cannot join
- Hereditary colorectal cancer syndromes (identified through genetic testing).
- Inflammatory bowel diseases.
- Lack of written informed consent.
Trial locations and contacts
6 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
6 sites in 5 countries
United States2 sites, 2 recruiting
- Recruiting
City of Hope Medical Center
Monrovia, California, 91016
Ajay Goel, PhD, 626-218-3452, AJGOEL@COH.ORG
Ajay Goel, PhD
- Recruiting
University of California San Diego
San Diego, California, 92093
C Richard Boland, MD, PhD
C Richard Boland, MD, PhD
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Dalian Medical University
Dalian
Jing Zhang
Jing Zhang
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele
Milan
Giulia Martina Cavestro, MD, PhD, cavestro.giuliamartina@hsr.it
Giulia Martina Cavestro
Spain1 site, 1 recruiting
- Recruiting
Barcelona University
Barcelona
Francesc Balaguer, MD, PhD, fprunes@clinic.cat
Francesc Balaguer
About this study
Official title: A Liquid Biopsy Assay For The Non-Invasive Early Detection of Advanced Adenomas and Colorectal Cancer
This study aims to develop a highly sensitive, specific, and cost-effective blood assay for early detection of colorectal adenomas and cancer, using advanced machine learning and state-of-the-art biological analyses.
Read the detailed description
Colorectal cancer (CRC) is a significant global health concern, ranking third in diagnosis and second in mortality. Despite being potentially preventable, it remains a leading cause of cancer-related deaths. Traditional screening methods like fecal immunochemical testing (FIT) have shown benefits in reducing late-stage diagnoses but have not effectively prevented CRC incidence. This is because tests like FIT can effectively detect the cancers, but not the precursor lesions, called adenomas. On the other hand, endoscopy-first approaches offer higher sensitivity for such adenomas and, therefore, lower the risk of developing CRC but face challenges such as invasiveness, cost, and patient compliance.
Non-invasive tests are more appealing to patients than invasive tests and can increase participation rates. Biomarker studies have shown promise, but existing tests lack sensitivity for early-stage CRC and advanced adenomas (AAs). This is likely because they assume the same analyte can detect both CRC and AAs, which may not be accurate due to differences in analyte release and the biological changes that occur during the adenoma-carcinoma sequence.
This study proposes developing an innovative liquid biopsy test tailored for AAs and CRC to address this. An ideal screening test should be minimally invasive, highly sensitive, and cost-effective. This test would optimize patient compliance and resource allocation by detecting both conditions from a single blood draw. More specifically, circulating microRNA (miRNA) analysis shows promise: tests based on cell-free microRNA (cf-miRNA) have demonstrated high sensitivity, while those based on exosome-derived microRNA (exo-miRNA) offer high specificity. Therefore, combining both analytes in a single test could maximize sensitivity and specificity.
This study will develop a non-invasive blood test for AA and CRC in four phases:
- Genome-wide profiling of cf-miRNA and exo-miRNA and selecting the best candidates for biomarker panels.
- Utilizing machine learning to identify promising candidates and train algorithms for detecting AAs and CRC separately, based on results from quantitative polymerase chain reaction (qPCR) analysis.
- Combining these algorithms to create detection signatures for both conditions.
- Independently validating these signatures using diverse cohorts to ensure broad applicability and compare the effectiveness of the blood assay to standard care through retrospective and prospective studies.
This study aims to develop a highly sensitive, specific, and cost-effective liquid biopsy for early detection of AAs and CRC. Success could transform clinical practice by preventing CRC through early detection of pre-malignant lesions. Innovations include incorporating pre-malignant lesions into screening and combining cf-miRNA and exo-miRNA biomarkers for accuracy. This approach could reduce CRC mortality and incidence and pave the way for new clinical trials.
- Conditions
- Colorectal Cancer, Colorectal Neoplasms, Colorectal Polyp, Colorectal Adenocarcinoma, Colorectal Disorders, Colorectal Dysplasia
- Being tested
- DENEB
- Keywords
- Early detection, Micro RNA, miRNA, Liquid biopsy, Machine learning, Artificial Intelligence, Incidence, Polypectomy, Screening, Surveillance, Exosome, Vascicles
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Polyposis Syndrome, Hereditary Mixed, 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DENEBDiagnostic test
Also called DENEB (DEtection of colorectal NEoplasias in Blood)
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
| Study group | Role | What they receive |
|---|---|---|
| Non-disease controls (Discovery cohort) | Individuals who underwent colonoscopy and were found not to have any adenomas or cancer. | |
| Low-risk Adenoma (Discovery cohort) | Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as all of the following: * 1 to 4 adenomas at most. * All adenomas have low-grade dysplasia at most. * All adenomas are <10 mm in diameter | |
| Advanced Adenoma (Discovery cohort) | Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following: * 5 or more adenomas. * One or more adenomas have high-grade dysplasia. * One or more adenomas are >10 mm in diameter | |
| Colorectal Cancer (Discovery cohort) | Individuals who underwent colonoscopy and were found to have colorectal cancer. | |
| Non-disease controls (Training cohort) | Individuals who underwent colonoscopy and were found not to have any adenomas or cancer. Receives: Diagnostic Test: DENEB | |
| Low-risk Adenoma (Training cohort) | Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as:
* 1 to 4 adenomas at most.
* All adenomas have low-grade dysplasia at most.
* All adenomas are <10 mm in diameter. Receives: Diagnostic Test: DENEB | |
| Advanced Adenoma (Training cohort) | Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following:
* 5 or more adenomas.
* One or more adenomas have high-grade dysplasia.
* One or more adenomas are >10 mm in diameter. Receives: Diagnostic Test: DENEB | |
| Colorectal Cancer (Training cohort) | Individuals who underwent colonoscopy and were found to have colorectal cancer. Receives: Diagnostic Test: DENEB | |
| Non-disease controls (Validation cohort) | Individuals who underwent colonoscopy and were found not to have any adenomas or cancer. Receives: Diagnostic Test: DENEB | |
| Low-risk Adenoma (Validation cohort) | Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as:
* 1 to 4 adenomas at most.
* All adenomas have low-grade dysplasia at most.
* All adenomas are <10 mm in diameter. Receives: Diagnostic Test: DENEB | |
| Advanced Adenoma (Validation cohort) | Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following:
* 5 or more adenomas.
* One or more adenomas have high-grade dysplasia.
* One or more adenomas are >10 mm in diameter. Receives: Diagnostic Test: DENEB | |
| Colorectal Cancer (Validation cohort) | Individuals who underwent colonoscopy and were found to have colorectal cancer. Receives: Diagnostic Test: DENEB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity
True positive rate: the probability of a positive test result, conditioned on the individual truly being positive
Measured: Through study completion, an average of 1 year
Secondary outcomes (2)
Specificity
True negative rate: the probability of a negative test result, conditioned on the individual truly being negative
Measured: Through study completion, an average of 1 year
Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy)
A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start15 Mar 2020
- Primary completion18 Jun 2028 (estimated)
- Study completion18 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ajay Goel, PhD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06342440
- Sponsor's protocol ID
- 23228/AACRC
- Acronym
- AACRC
- Status last verified
- Jul 2026
- First submitted
- 26 Mar 2024
- Last updated
- 7 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.
Publications
Ahlquist DA, Sargent DJ, Loprinzi CL, Levin TR, Rex DK, Ahnen DJ, Knigge K, Lance MP, Burgart LJ, Hamilton SR, Allison JE, Lawson MJ, Devens ME, Harrington JJ, Hillman SL. Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med. 2008 Oct 7;149(7):441-50, W81. doi: 10.7326/0003-4819-149-7-200810070-00004.
PubMed 18838724Aziz Z, Wagner S, Agyekum A, Pumpalova YS, Prest M, Lim F, Rustgi S, Kastrinos F, Grady WM, Hur C. Cost-Effectiveness of Liquid Biopsy for Colorectal Cancer Screening in Patients Who Are Unscreened. JAMA Netw Open. 2023 Nov 1;6(11):e2343392. doi: 10.1001/jamanetworkopen.2023.43392.
PubMed 37971743Barnell EK, Kang Y, Wurtzler EM, Griffith M, Chaudhuri AA, Griffith OL; Geneoscopy Scientists. Noninvasive Detection of High-Risk Adenomas Using Stool-Derived Eukaryotic RNA Sequences as Biomarkers. Gastroenterology. 2019 Sep;157(3):884-887.e3. doi: 10.1053/j.gastro.2019.05.058. Epub 2019 May 30. No abstract available.
PubMed 31154021Barnell EK, Wurtzler EM, La Rocca J, Fitzgerald T, Petrone J, Hao Y, Kang Y, Holmes FL, Lieberman DA. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023 Nov 14;330(18):1760-1768. doi: 10.1001/jama.2023.22231.
PubMed 37870871Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.
PubMed 24553385Bosch LJW, de Wit M, Pham TV, Coupe VMH, Hiemstra AC, Piersma SR, Oudgenoeg G, Scheffer GL, Mongera S, Sive Droste JT, Oort FA, van Turenhout ST, Larbi IB, Louwagie J, van Criekinge W, van der Hulst RWM, Mulder CJJ, Carvalho B, Fijneman RJA, Jimenez CR, Meijer GA. Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case-Control Study. Ann Intern Med. 2017 Dec 19;167(12):855-866. doi: 10.7326/M17-1068. Epub 2017 Nov 21.
PubMed 29159365Brenner H, Heisser T, Cardoso R, Hoffmeister M. Reduction in colorectal cancer incidence by screening endoscopy. Nat Rev Gastroenterol Hepatol. 2024 Feb;21(2):125-133. doi: 10.1038/s41575-023-00847-3. Epub 2023 Oct 4.
PubMed 37794234Carethers JM. Stool-Based Screening Tests for Colorectal Cancer. JAMA. 2023 Mar 14;329(10):839-840. doi: 10.1001/jama.2023.0547.
PubMed 36800187Carethers JM. Improving Noninvasive Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):1045-1046. doi: 10.1056/NEJMe2400366. No abstract available.
PubMed 38477992Chung 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.
PubMed 38477985Church TR, Wandell M, Lofton-Day C, Mongin SJ, Burger M, Payne SR, Castanos-Velez E, Blumenstein BA, Rosch T, Osborn N, Snover D, Day RW, Ransohoff DF; PRESEPT Clinical Study Steering Committee, Investigators and Study Team. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014 Feb;63(2):317-25. doi: 10.1136/gutjnl-2012-304149. Epub 2013 Feb 13.
PubMed 23408352de Klaver W, Wisse PHA, van Wifferen F, Bosch LJW, Jimenez CR, van der Hulst RWM, Fijneman RJA, Kuipers EJ, Greuter MJE, Carvalho B, Spaander MCW, Dekker E, Coupe VMH, de Wit M, Meijer GA. Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening : A Diagnostic Test Accuracy Study. Ann Intern Med. 2021 Sep;174(9):1224-1231. doi: 10.7326/M20-8270. Epub 2021 Jul 20.
PubMed 34280333de Klerk CM, Wieten E, Lansdorp-Vogelaar I, Bossuyt PM, Spaander MC, Dekker E. Performance of two faecal immunochemical tests for the detection of advanced neoplasia at different positivity thresholds: a cross-sectional study of the Dutch national colorectal cancer screening programme. Lancet Gastroenterol Hepatol. 2019 Feb;4(2):111-118. doi: 10.1016/S2468-1253(18)30319-4. Epub 2018 Nov 27.
PubMed 30497962Fu B, Yan P, Zhang S, Lu Y, Pan L, Tang W, Chen S, Chen S, Zhang A, Liu W. Cell-Free Circulating Methylated SEPT9 for Noninvasive Diagnosis and Monitoring of Colorectal Cancer. Dis Markers. 2018 Apr 23;2018:6437104. doi: 10.1155/2018/6437104. eCollection 2018.
PubMed 29849824Gagrat ZD, Krockenberger M, Bhattacharya A, Gagrat BZ, Leduc CM, Matter MB, Fourrier KD, Mahoney DW, Edwards V DK, Lidgard GP, Limburg PJ, Johnson SC, Domanico MJ, Kisiel JB. Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions. Cancer Prev Res (Phila). 2024 Mar 4;17(3):119-126. doi: 10.1158/1940-6207.CAPR-23-0285.
PubMed 38224564