Study Aiming to Test Whether Non-invasive Liquid Biopsies Can Safely Reduce Invasive Surveillance Methods in Lynch Syndrome

NCT07360834 | Not Yet Recruiting DMC

• 2 other identifiers: UC-GIG-2522Project 101213916
• Study Type: interventional
• Target: 2,000
• Locations: 9 countries
• Sites: 9

Brief Summary

Lynch syndrome is an inherited genetic predisposition that increases the risk of developing several types of cancer, particularly colon and rectal cancers (colorectal cancer), as well as cancer of the uterine lining (endometrial cancer). It affects around 1 in 400 people in Europe. Today, surveillance mainly relies on examinations such as colonoscopy (an examination of the colon using a camera) or gynaecological evaluations, sometimes accompanied by biopsies (the removal of a small tissue sample for microscopic analysis). Although effective, these procedures are invasive and demanding; they can affect quality of life and discourage some individuals from adhering to their recommended surveillance programme. The European project PREDI-LYNCH is exploring an additional pathway that is simpler and better tolerated. This project relies on "liquid biopsies", meaning tests performed on easily collected samples such as blood, urine, stool, and vaginal swabs for women with a uterus. The PREDI-LYNCH study aims to determine whether these non-invasive tests could enable personalised surveillance and potentially increase the interval between more burdensome procedures, while maintaining a high level of medical safety.

Conditions

Lynch Syndrome

Keywords

Lynch Syndrome, hereditary cancer, MMR deficiency, Liquid biopsies, cancer early detection.; Lynch Syndrome, MMR deficiency, Liquid biopsies

Outcome Measures

Primary Outcomes (1)

• To determine whether a multimodal surveillance strategy - using combining concurrent circulating tumor DNA (ctDNA), urine tumor DNA (utDNA), vaginal swab tumor DNA (vsDNA), and stool (qFIT) - is non-inferior to standard-of-care screening surveillance

  Number of newly diagnosed histologically confirmed invasive cancers (CRC, EC, UC) during surveillance and follow-up phases, expressed as cumulative incidence (%) and incidence per 1,000 person-years.

  Baseline, month 12, month 24, month 36, month 48

Study Arms (2)

Experimental arm

EXPERIMENTAL

Biopsies Liquids +/- Colonoscopy

Diagnostic Test: INVITRO DIAGNOSTIC TESTS AND COLONOSCOPY

Control arm

OTHER

Colonoscopy each 18 months

Diagnostic Test: INVITRO DIAGNOSTIC TESTS AND COLONOSCOPY

Interventions

INVITRO DIAGNOSTIC TESTS AND COLONOSCOPY DIAGNOSTIC_TEST

The trial compares two strategies: standard follow-up with colonoscopy every 18 months versus an approach combining annual liquid biopsies with a colonoscopy every 36 months

Control arm; Experimental arm

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Age 35-80
• Genetically confirmed class 4-5 (likely pathogenic (LP) or pathogenic (P) variant, respectively) in MLH1, MSH2, MSH6, or EPCAM gene.
• The participant should be insurance covered for the financial costs of the standard surveillance and healthcare related to LS, such as affiliated to Social Security System

You may not qualify if:

• Previously performed proctocolectomy or equivalent (entire colon and rectum removed)
• Checkpoint inhibitor therapy within 12 months
• Pregnancy
• Participants unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
• Persons deprived of their liberty or under protective custody or guardianship.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (9)

Klinicki Bolnicki Centar Sestre Milosrdnice Ustanova

Zagreb, Croatia

Location

Masaryk Memorial Cancer Institute

Brno, Czechia

Location

Tampereen Korkeakoulusäätiö SR

Helsinki, Finland

Location

GGC Network

Paris, France

Location

Ist. Tumori di Milano

Milan, Italy

Location

Pauls Stradins Clinical University Hospital

Riga, Latvia

Location

Erasmus Medisch Centrum Rotterdam

Rotterdam, Netherlands

Location

Oslo University Hospital

Oslo, Norway

Location

University of Edinburgh

Edinburgh, United Kingdom

Location

Related Publications (6)

• Gallon R, Brekelmans C, Martin M, Bours V, Schamschula E, Amberger A, Muleris M, Colas C, Dekervel J, De Hertogh G, Coupier J, Colleye O, Sepulchre E, Burn J, Brems H, Legius E, Wimmer K. Constitutional mismatch repair deficiency mimicking Lynch syndrome is associated with hypomorphic mismatch repair gene variants. NPJ Precis Oncol. 2024 May 24;8(1):119. doi: 10.1038/s41698-024-00603-z.

  PMID: 38789506 BACKGROUND

• Wu J, Lin Y, Yang K, Liu X, Wang H, Yu T, Tao R, Guo J, Chen L, Cheng H, Lou F, Cao S, Yu W, Hu H, Ye D. Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial. Mol Cancer. 2024 Mar 19;23(1):57. doi: 10.1186/s12943-024-01974-4.

  PMID: 38504268 BACKGROUND

• Willis J, Lefterova MI, Artyomenko A, Kasi PM, Nakamura Y, Mody K, Catenacci DVT, Fakih M, Barbacioru C, Zhao J, Sikora M, Fairclough SR, Lee H, Kim KM, Kim ST, Kim J, Gavino D, Benavides M, Peled N, Nguyen T, Cusnir M, Eskander RN, Azzi G, Yoshino T, Banks KC, Raymond VM, Lanman RB, Chudova DI, Talasaz A, Kopetz S, Lee J, Odegaard JI. Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel. Clin Cancer Res. 2019 Dec 1;25(23):7035-7045. doi: 10.1158/1078-0432.CCR-19-1324. Epub 2019 Aug 4.

  PMID: 31383735 BACKGROUND

• van Liere ELSA, Jacobs IL, Dekker E, Jacobs MAJM, de Boer NKH, Ramsoekh D. Colonoscopy surveillance in Lynch syndrome is burdensome and frequently delayed. Fam Cancer. 2023 Oct;22(4):403-411. doi: 10.1007/s10689-023-00333-4. Epub 2023 May 12.

  PMID: 37171677 BACKGROUND

• Moller P, Seppala T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rodland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen J, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer JP, Pylvanainen K, Sampson JR, Capella G, Mecklin JP, Moslein G; Mallorca Group (http://mallorca-group.eu). Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017 Mar;66(3):464-472. doi: 10.1136/gutjnl-2015-309675. Epub 2015 Dec 9.

  PMID: 26657901 BACKGROUND

• Stoffel EM, Murphy CC. Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults. Gastroenterology. 2020 Jan;158(2):341-353. doi: 10.1053/j.gastro.2019.07.055. Epub 2019 Aug 5.

  PMID: 31394082 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis; Turcot syndrome

Interventions

Colonoscopy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Chrystelle Colas, Oncogeneticist

  Institut Curie

  STUDY DIRECTOR

• Toni Seppala, Surgeon

  TAMPERE University (Finland)

  STUDY DIRECTOR

Central Study Contacts

Amina Ghorbel, PhD

CONTACT

+33 (0) 6 68 50 20 12; a-ghorbel@unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 22, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030
• Last Updated: January 23, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); GB (1); NO (1); LA (1); CR (1); CZ (1); FR (1); IT (1); NL (1)