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

Официальное название

Predicting Cancer Onset in Lynch Syndrome by Liquid Biopsies

Обзор

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.

Подробное описание

This European clinical study evaluates whether non-invasive liquid biopsy tests (blood, urine, stool and vaginal samples when applicable) can improve cancer surveillance in adults with genetically confirmed Lynch syndrome (MLH1, MSH2, MSH6 or EPCAM). 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. The main outcome is the number of new cancer cases diagnosed, confirmed by standard procedures. Secondary outcomes include early cancer detection, lesion identification, diagnostic timing, feasibility, quality of life and healthcare use. Each positive test leads to fast confirmatory exams. The aim is to determine if liquid biopsies can safely reduce invasive procedures while maintaining effective cancer monitoring.

Вмешательства

• Диагностический тест INVITRO DIAGNOSTIC TESTS AND COLONOSCOPY
  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

Первичные конечные точки

• 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 [Срок оценки: Baseline, month 12, month 24, month 36, month 48]

Критерии участия

Критерии включения

• 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

Критерии исключения

• Previously performed proctocolectomy or equivalent (entire colon and rectum removed)
• Active treatment for cancer within 2 years prior to inclusion.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Хорватия · 1 центр

• Klinicki Bolnicki Centar Sestre Milosrdnice Ustanova — Zagreb

Чехия · 1 центр

• Masaryk Memorial Cancer Institute — Brno

Финляндия · 1 центр

• Tampereen Korkeakoulusäätiö SR — Helsinki

Франция · 1 центр

• GGC Network — Paris

Италия · 1 центр

• Ist. Tumori di Milano — Milan

Латвия · 1 центр

• Pauls Stradins Clinical University Hospital — Riga

Нидерланды · 1 центр

• Erasmus Medisch Centrum Rotterdam — Rotterdam

Норвегия · 1 центр

• Oslo University Hospital — Oslo

Великобритания · 1 центр

• University of Edinburgh — Edinburgh

Публикации

• 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
• 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
• 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 Com PMID 31383735
• 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
• 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 PMID 26657901
• 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

Идентификаторы

NCT: NCT07360834 · UC-GIG-2522 · Project 101213916

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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