Clinical trial NCT06989814: Smart Measurement of Circulating Tumor DNA
Official title: Smart Measurement of Circulating Tumor DNA: a Tumor-agnostic Computational Tool to Improve Colorectal Cancer Care
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Neoplasms
Colorectal Neoplasms Malignant
Colorectal Neoplasms, Hereditary Nonpolyposis
Hereditary Nonpolyposis Colon Cancer
Keywords: Liquid Biopsy
Colorectal cancer
Early detection
Prevention
Surveillance
Screening
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
name: Leiden University Medical Center
First posted: 2025-05-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Case-control study.
Primary purpose: SCREENING

Brief summary: The goal of this study is to develop a blood-test which can detect colorectal cancer in early stages.

Participants will be asked to take an extra blood test, which will be analyzed further in the lab.

Detailed description: Lynch Syndrome (LS) carriers have a predisposition to develop various types of cancer, especially colorectal cancer (CRC) and endometrial cancer (EC). LS patients are advised to undergo surveillance by colonoscopy every 2 year and gynaecological surveillance. This surveillance is deemed burdensome and fails to detect a small part of the developing CRCs and the majority of extra-colonic cancers. To ensure prevention and early detection of cancer, a reliable and accessible test is needed. Recent studies have shown the potential of the detection of tumor-derived DNA fragments (circulating tumor DNA; ctDNA). Various molecular characteristics can be used to discriminate ctDNA from healthy circulating cell-free DNA. Current ctDNA assays with the highest sensitivity and specificity to detect for example minimal residual disease (MRD) after surgery are mostly tumor-informed, which means prior information is needed from the tumor tissue about the molecular alterations present.

As this information is not available for the detection of newly arising tumors, the aim of this study is to evaluate the use of an optimized combination of tumor agnostic ctDNA characteristics for the detection of newly developing tumors.

Eligibility criteria: Inclusion Criteria:

(suspect) Lynch Syndrome carriers who:

* Have proven Lynch Syndrome (MMR-gene or EPCAM mutation), or have a proven microsatellite instability high (MSI-H)tumor;
* Are at least 18 years old; Have been diagnosed with any form of cancer at the time of inclusion, but have had no treatment yet;
* Have granted informed consent to participate in this study.

Exclusion Criteria:

(suspect) Lynch Syndrome carriers who:

* Are unwilling to undergo extra blood sampling;
* Are under the age of 18;
* Have no newly diagnosed tumors at time of inclusion;
* Have been treated for their tumor at time of inclusion;
* Are not able to read or understand Dutch language or are mentally not capable.

Primary outcomes:
measure: Estimated ctDNA fractions in blood
timeFrame: Measurement at baseline
measure: Tumor pathology
timeFrame: Measurement at baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
Study officials:
affiliation: Erasmus Medical Center
name: Anja Wagner, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mouliere F, Chandrananda D, Piskorz AM, Moore EK, Morris J, Ahlborn LB, Mair R, Goranova T, Marass F, Heider K, Wan JCM, Supernat A, Hudecova I, Gounaris I, Ros S, Jimenez-Linan M, Garcia-Corbacho J, Patel K, Ostrup O, Murphy S, Eldridge MD, Gale D, Stewart GD, Burge J, Cooper WN, van der Heijden MS, Massie CE, Watts C, Corrie P, Pacey S, Brindle KM, Baird RD, Mau-Sorensen M, Parkinson CA, Smith CG, Brenton JD, Rosenfeld N. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med. 2018 Nov 7;10(466):eaat4921. doi: 10.1126/scitranslmed.aat4921.
citation: Deger T, Boers RG, de Weerd V, Angus L, van der Put MMJ, Boers JB, Azmani Z, van IJcken WFJ, Grunhagen DJ, van Dessel LF, Lolkema MPJK, Verhoef C, Sleijfer S, Martens JWM, Gribnau J, Wilting SM. High-throughput and affordable genome-wide methylation profiling of circulating cell-free DNA by methylated DNA sequencing (MeD-seq) of LpnPI digested fragments. Clin Epigenetics. 2021 Oct 20;13(1):196. doi: 10.1186/s13148-021-01177-4.
citation: Schrag D, Beer TM, McDonnell CH 3rd, Nadauld L, Dilaveri CA, Reid R, Marinac CR, Chung KC, Lopatin M, Fung ET, Klein EA. Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Lancet. 2023 Oct 7;402(10409):1251-1260. doi: 10.1016/S0140-6736(23)01700-2.
citation: Eikenboom EL, Wilting SM, Deger T, Srebniak MI, Van Veghel-Plandsoen M, Boers RG, Boers JB, van IJcken WFJ, Gribnau JH, Atmodimedjo P, Dubbink HJ, Martens JWM, Spaander MCW, Wagner A. Liquid Biopsies for Colorectal Cancer and Advanced Adenoma Screening and Surveillance: What to Measure? Cancers (Basel). 2023 Sep 17;15(18):4607. doi: 10.3390/cancers15184607.