NCT07450612

Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 1,200 (estimated)
• Sponsor: San Raffaele University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Detailed description

Colorectal cancer (CRC) remains a significant public health burden as the third-most commonly diagnosed and second-deadliest malignancy. While CRC is potentially preventable through the removal of precursor lesions known as advanced adenomas (AAs), current screening modalities have limitations. The fecal immunochemical test (FIT) exhibits reduced sensitivity for early-stage CRC and AAs, primarily lowering mortality rather than incidence. Colonoscopy, while effective, is invasive, costly, and suffers from suboptimal adherence. Additionally, individuals with Lynch syndrome (LS), who carry a pathogenic germline variant in mismatch repair (MMR) genes, lack effective and reliable methods for early-stage detection of non-CRC tumors associated with the syndrome. The rationale of this study, BEACON/2026, is to develop and validate two blood-based tests to address these clinical gaps. The first is a screening test sensitive to both CRC and AAs to complement existing screening options; the second is a multi-cancer early detection (MCED) test tailored to the LS spectrum. The central hypothesis is that a liquid biopsy approach combining cell-free microRNAs (cf-miRNAs, which are sensitive) and exosome-bound microRNAs (exo-miRNAs, which are specific) can effectively distinguish patients with AAs, CRC, and LS-associated cancers from controls. This study follows the Early Detection Research Network (EDRN) recommendations for biomarker development, including biomarker discovery, prioritization, training, and independent validation (Phases I through III). The experimental design complies with PROBE recommendations for prospectively collected biospecimens that are blindly evaluated. The procedure involves the collection of peripheral blood to isolate RNA from plasma or serum for reverse transcription, quantitative polymerase chain reaction (RT-qPCR) analysis and machine-learning modeling . This non-invasive approach aims to provide a cost-effective, patient-friendly alternative to improve screening participation and disease monitoring

Conditions

• Colorectal Cancer
• Adenoma Colon
• Adenoma Colon Polyp
• Colon Adenoma
• Colo-rectal Cancer
• Colon Disease
• Colon Neoplasm
• Lynch Syndrome
• Lynch Syndrome I
• Lynch Syndrome II
• Lynch Syndrome I (Site-specific Colonic Cancer)
• LYN Gene Mutation
• Mismatch Repair Deficiency
• Mismatch Repair Gene Mutation
• MLH1 Gene Mutation
• MSH2 Gene Mutation
• MSH6 Gene Mutation
• PMS2 Gene Mutation
• EPCAM Gene Mutation

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	BEACON	A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples

Timeline

• Start date: 2024-01-01
• Primary completion: 2031-01-15
• Completion: 2031-08-15
• First posted: 2026-03-04
• Last updated: 2026-03-04

Locations

4 sites across 1 country: Italy