NCT07450612

Brief Summary

This is an multicenter study that will test the diagnostic accuracy of a blood test (i.e., a liquid biopsy) for the diagnosis of colorectal cancer (CRC), advanced adenomas (AAs), as well as Lynch-syndrome associated cancers. Additionally, a pre-planned analysis will evaluate the use of this liquid biopsy as a tool for molecular residual disease monitoring purposes.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,200

participants targeted

Target at P75+ for all trials

Timeline
61mo left

Started Jan 2024

Longer than P75 for all trials

Geographic Reach
1 country

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Jan 2024Aug 2031

Study Start

First participant enrolled

January 1, 2024

Completed
2.2 years until next milestone

First Submitted

Initial submission to the registry

February 27, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 4, 2026

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2031

Expected
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2031

Last Updated

March 4, 2026

Status Verified

February 1, 2026

Enrollment Period

7 years

First QC Date

February 27, 2026

Last Update Submit

February 27, 2026

Conditions

Adenoma ColonAdenoma Colon PolypColon AdenomaColo-rectal CancerColon DiseaseColon NeoplasmLynch SyndromeLynch Syndrome ILynch Syndrome IILYN Gene MutationMismatch Repair DeficiencyMismatch Repair Gene MutationMLH1 Gene MutationMSH2 Gene MutationMSH6 Gene MutationPMS2 Gene MutationEPCAM Gene MutationLynch Syndrome I (Site-specific Colonic Cancer)

Outcome Measures

Primary Outcomes (1)

  • Sensitivity

    True positive rate: the probability of a positive test result, conditioned on the individual truly being positive

    Through study completion, an average of 1 year

Secondary Outcomes (2)

  • Specificity

    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)

    Through study completion, an average of 1 year

Study Arms (7)

Lynch syndrome, without Lynch-syndrome associated cancers

Individuals with Lynch syndrome, who are free of Lynch-syndrome associated cancers at the time of blood drawing

Diagnostic Test: BEACON

Lynch syndrome, with Lynch-syndrome associated cancers

Individuals with Lynch syndrome, who have one (or more) Lynch-syndrome associated cancer(s) at the time of blood drawing

Diagnostic Test: BEACON

Colorectal cancer

Individuals with sporadic biopsy-proven colorectal cancer, as identified during routine colonoscopy and diagnosed via pathological review

Diagnostic Test: BEACON

Advanced adenoma

Individuals with sporadic advanced adenomas, defined as (i) more than 3 colorectal polyps, (ii) presence of high-grade dysplasia in one or more polyp, or (iii) polyp(s) \>10 mm

Diagnostic Test: BEACON

Colonoscopy-negative controls

Individuals whose colonoscopy was negative for colorectal cancer and for advanced colorectal adenomas

Diagnostic Test: BEACON

Pre-treatment samples

Individuals with (i) colorectal cancer, or (ii) advanced adenomas, or (iii) Lynch syndrome associated cancer(s) will have the possibility to participate to a sub-analysis of this study, where their circulating plasma levels of biomarkers will be evaluated prior to resection (treatment-naive) and post-resection (to measure the molecular persistence of the disease after the resection)

Diagnostic Test: BEACON

Post-treatment samples

Individuals with (i) colorectal cancer, or (ii) advanced adenomas, or (iii) Lynch syndrome associated cancer(s) will have the possibility to participate to a sub-analysis of this study, where their circulating plasma levels of biomarkers will be evaluated prior to resection (treatment-naive) and post-resection (to measure the molecular persistence of the disease after the resection)

Diagnostic Test: BEACON

Interventions

BEACONDIAGNOSTIC_TEST

A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples

Advanced adenomaColonoscopy-negative controlsColorectal cancerLynch syndrome, with Lynch-syndrome associated cancersLynch syndrome, without Lynch-syndrome associated cancersPost-treatment samplesPre-treatment samples

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Seven independent cohorts of individuals who belong to one of the following seven: * Lynch syndrome, without any Lynch-syndrome-associated cancer * Lynch syndrome, with one or more Lynch-syndrome-associated cancer(s) * Sporadic colorectal cancer * Sporadic advanced adenoma (at most) * Colonoscopy-negative controls * Treatment-naive blood samples * Post-treatment blood samples

You may qualify if:

  • 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

You may not qualify if:

  • Lack of informed consent
  • Inflammatory bowel disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Gastronterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Hospital

Milan, Lombardy, 20132, Italy

NOT YET RECRUITING

Prof Giulia Martina Cavestro, MD PhD

Milan, Lombardy, 20132, Italy

NOT YET RECRUITING

San Raffaele Scientific Institute, Gastroenterology and Gastrointestinal Endoscopy Unit

Milan, Lombardy, 20132, Italy

RECRUITING

Dipartimento di Chirurgia Oncologica e Dipartimento di Oncologia Sperimentale Istituto Nazionale Tumori

Milan, MI, Italy

NOT YET RECRUITING

Related Publications (21)

  • 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.

    PMID: 18838724BACKGROUND

  • Aziz 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.

    PMID: 37971743BACKGROUND

  • Barnell 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.

    PMID: 31154021BACKGROUND

  • Barnell 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.

    PMID: 37870871BACKGROUND

  • Bettegowda 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.

    PMID: 24553385BACKGROUND

  • Carethers JM. Stool-Based Screening Tests for Colorectal Cancer. JAMA. 2023 Mar 14;329(10):839-840. doi: 10.1001/jama.2023.0547.

    PMID: 36800187BACKGROUND

  • 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.

    PMID: 38477985BACKGROUND

  • Imperiale TF, Porter K, Zella J, Gagrat ZD, Olson MC, Statz S, Garces J, Lavin PT, Aguilar H, Brinberg D, Berkelhammer C, Kisiel JB, Limburg PJ; BLUE-C Study Investigators. Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):984-993. doi: 10.1056/NEJMoa2310336.

    PMID: 38477986BACKGROUND

  • Mannucci A, Balaguer F, Yamada Y, Nagasaka T, Toiyama Y, Okugawa Y, Marti-Gallostra M, Jimenez-Toscano M, Vidal-Tocino R, Jimenez F, Perea J, Quintero E, Boland CR, Cavestro GM, Goel A; SECOC-ENCODER Collaborators. An Exosome-Based Liquid Biopsy for the Detection of Early-Onset Colorectal Cancer: The ENCODER Multicenter Study. Gastroenterology. 2026 Feb;170(2):330-343. doi: 10.1053/j.gastro.2025.08.013. Epub 2025 Dec 9.

    PMID: 41364052BACKGROUND

  • Mannucci A, Goel A. Circulating Tumor DNA-Based Blood Test for Colorectal Cancer Screening. JAMA. 2025 Nov 11;334(18):1680-1681. doi: 10.1001/jama.2025.14109. No abstract available.

    PMID: 41060624BACKGROUND

  • Mannucci A, Hernandez G, Uetake H, Yamada Y, Balaguer F, Baba H, Chen T, Chen J, Boland CR, Cavestro GM, Quintero E, Goel A. Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study. NPJ Precis Oncol. 2025 Jun 21;9(1):202. doi: 10.1038/s41698-025-00978-7.

    PMID: 40544180BACKGROUND

  • Negro S, Perissinotto E, Mammi I, Crivellari G, Schiavi F, Cappello F, Spolverato G, Ferrari D, Rausa E, Vitellaro M, Fassan M, Cavestro GM, Mannucci A, Lonardi S, Bergamo F, Urso EDL. Emerging therapeutic strategies in Lynch syndrome-associated colorectal cancer and the role of MMR testing. Tumori. 2025 Jan 30:3008916241310706. doi: 10.1177/03008916241310706. Online ahead of print.

    PMID: 39882759BACKGROUND

  • Xu C, Mannucci A, Esposito F, Oliveres H, Alonso-Orduna V, Yubero A, Fernandez-Martos C, Salud A, Gallego J, Martin-Richard M, Fernandez-Plana J, Guillot M, Aparicio J, Fakih M, Kopetz S, Feliu J, Maurel J, Goel A. An Exosome-Based Liquid Biopsy Predicts Depth of Response and Survival Outcomes to Cetuximab and Panitumumab in Metastatic Colorectal Cancer: The EXONERATE Study. Clin Cancer Res. 2025 Mar 17;31(6):1002-1015. doi: 10.1158/1078-0432.CCR-24-1934.

    PMID: 39820673BACKGROUND

  • Mannucci A, Goel A. Stool and blood biomarkers for colorectal cancer management: an update on screening and disease monitoring. Mol Cancer. 2024 Nov 19;23(1):259. doi: 10.1186/s12943-024-02174-w.

    PMID: 39558327BACKGROUND

  • Mannucci A, Goel A. Stool and Blood DNA Tests for Colorectal Cancer Screening. N Engl J Med. 2024 Jun 20;390(23):2224. doi: 10.1056/NEJMc2404924. No abstract available.

    PMID: 38899710BACKGROUND

  • Shiu PKT, DiStefano JK, Alahari SK, Enguita FJ, Feinberg MW, Sideris N, Bayraktar S, Castellano L, Buitrago DL, Caporali A, Mannucci A, Goel A. The Non-Coding RNA Journal Club: Highlights on Recent Papers-13. Noncoding RNA. 2023 Dec 14;9(6):76. doi: 10.3390/ncrna9060076.

    PMID: 38133210BACKGROUND

  • Cavestro GM, Mannucci A, Balaguer F, Hampel H, Kupfer SS, Repici A, Sartore-Bianchi A, Seppala TT, Valentini V, Boland CR, Brand RE, Buffart TE, Burke CA, Caccialanza R, Cannizzaro R, Cascinu S, Cercek A, Crosbie EJ, Danese S, Dekker E, Daca-Alvarez M, Deni F, Dominguez-Valentin M, Eng C, Goel A, Guillem JG, Houwen BBSL, Kahi C, Kalady MF, Kastrinos F, Kuhn F, Laghi L, Latchford A, Liska D, Lynch P, Malesci A, Mauri G, Meldolesi E, Moller P, Monahan KJ, Moslein G, Murphy CC, Nass K, Ng K, Oliani C, Papaleo E, Patel SG, Puzzono M, Remo A, Ricciardiello L, Ripamonti CI, Siena S, Singh SK, Stadler ZK, Stanich PP, Syngal S, Turi S, Urso ED, Valle L, Vanni VS, Vilar E, Vitellaro M, You YN, Yurgelun MB, Zuppardo RA, Stoffel EM; Associazione Italiana Familiarita Ereditarieta Tumori; Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; European Hereditary Tumour Group, and the International Society for Gastrointestinal Hereditary Tumours. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines. Clin Gastroenterol Hepatol. 2023 Mar;21(3):581-603.e33. doi: 10.1016/j.cgh.2022.12.006. Epub 2022 Dec 20.

    PMID: 36549470BACKGROUND

  • Russo M, Barchi A, Mannucci A, Puzzono M, Zuppardo RA, Biamonte P, Bencardino S, Leandro G, Cannizzaro R, Monica F, Zagari RM, Pasquale L, Goni E, Di Leo M, Ricciardiello L, Cavestro GM; Italian Society of Gastroenterology (AIGO), Italian Society of Digestive Endoscopy (SIED) and Italian Society of Gastroenterology and Digestive Endoscopy (SIGE). Increased Number of Colorectal Interval Cancers in Lynch Syndrome after the SARS-CoV-2 Pandemic: A Survey-Based Study. Dig Dis. 2023;41(2):227-232. doi: 10.1159/000524393. Epub 2022 Apr 25.

    PMID: 35468603BACKGROUND

  • Puzzono M, Mannucci A, Di Leo M, Zuppardo RA, Russo M, Ditonno I, Goni E, Notaristefano C, Azzolini F, Fanti L, Viale E, Elmore U, Pantaleo G, Cascinu S, Rosati R, Cavestro GM. Diet and Lifestyle Habits in Early-Onset Colorectal Cancer: A Pilot Case-Control Study. Dig Dis. 2022;40(6):710-718. doi: 10.1159/000521932. Epub 2022 Jan 27.

    PMID: 35086089BACKGROUND

  • Mannucci A, Zuppardo RA, Crippa S, Carrera P, Patricelli MG, Russo Raucci A, Calabrese F, Lazarevic D, Giannese F, Tonon G, Ferrari M, Testoni PA, Cavestro GM. MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer. Eur J Gastroenterol Hepatol. 2020 Mar;32(3):345-349. doi: 10.1097/MEG.0000000000001617.

    PMID: 31851094BACKGROUND

  • Cavestro GM, Zuppardo RA, Mannucci A. Early-onset colorectal cancer: trends and challenges. Lancet Gastroenterol Hepatol. 2019 Jul;4(7):491-492. doi: 10.1016/S2468-1253(19)30146-3. Epub 2019 May 16. No abstract available.

    PMID: 31105046BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and serum samples

MeSH Terms

Conditions

Colorectal NeoplasmsColonic NeoplasmsColonic DiseasesColorectal Neoplasms, Hereditary NonpolyposisLynch Syndrome IILynch syndrome I (site-specific colonic cancer)Turcot syndrome

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal DiseasesNeoplastic Syndromes, HereditaryGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesDNA Repair-Deficiency DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Giulia Martina Cavestro, MD, PhD

    IRCCS San Raffaele Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Giulia Martina Cavestro, MD, PhD

CONTACT

0226437217cavestro.giuliamartina@hsr.it

Giulia Martina Cavestro

CONTACT

0226437217cavestro.giuliamartina@hsr.it

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 27, 2026

First Posted

March 4, 2026

Study Start

January 1, 2024

Primary Completion (Estimated)

January 15, 2031

Study Completion (Estimated)

August 15, 2031

Last Updated

March 4, 2026

Record last verified: 2026-02

Locations

IT(4)