Urine Tumor DNA Test for Lynch Syndrome

Recruiting at 1 trial location

Overseen By Jussi Nikkola, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Tampere University Hospital

Disqualifiers: Concurrent urothelial carcinoma

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover a new method for early detection of urothelial cancers in individuals with Lynch syndrome, a genetic condition that raises cancer risk. The trial employs a urine tumor DNA test to identify these cancers before symptoms emerge. Individuals diagnosed with Lynch syndrome and aged between 50 and 75 may be suitable candidates. The goal is to determine if this early detection method can identify cancers while they remain treatable. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could lead to earlier cancer detection and improved outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this urine tumor DNA test is safe for screening?

Research has shown that using urine tests to check for cancer in people with Lynch syndrome is generally well-received. So far, no serious side effects have been reported from this type of testing, suggesting it is safe for participants.

Other studies have used similar DNA-based screening methods without major safety concerns. Although researchers are still studying this test, the absence of reported problems is encouraging for those considering joining the study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way of screening for urothelial cancer in people with Lynch syndrome using a urine tumor DNA test. Unlike traditional methods like colonoscopy or endoscopic exams, which can be invasive and uncomfortable, this test offers a non-invasive alternative. It works by detecting tumor DNA in urine, potentially allowing for earlier and more convenient detection of cancer. This innovative approach could improve screening experiences and outcomes for patients, making it a promising development in cancer detection.

What evidence suggests that the urine tumor DNA test is effective for detecting urothelial cancer in Lynch syndrome patients?

Research shows that the urine tumor DNA (utDNA) test, which participants in this trial will undergo, might help detect urothelial cancers early in people with Lynch syndrome. Studies have found that cancers linked to Lynch syndrome often exhibit high levels of microsatellite instability (MSI), and the utDNA test is designed to identify this in urine samples. This method can detect cancers before symptoms appear, allowing for early treatment. Early detection is crucial because Lynch syndrome significantly increases the risk of bladder and kidney cancers. Overall, the utDNA test appears promising as a non-invasive way to catch these cancers early in high-risk individuals. ^{1 3 6 7 8}

Who Is on the Research Team?

Jussi Nikkola

Principal Investigator

Tampere University Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with Lynch Syndrome, a genetic condition that increases cancer risk. It's focused on detecting urothelial cancers early, which include bladder and upper urinary tract tumors. Participants should have this inherited syndrome but no current symptoms of urothelial cancer.

Inclusion Criteria

I am between 50 and 75 years old.

Willing and able to provide informed consent

I have been diagnosed with Lynch syndrome.

Exclusion Criteria

I have urothelial carcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Screening Arm

Invitation to participate in urothelial cancer screening and questionnaires

1 year

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after screening

10 years

Regular follow-up visits at 2, 5, and 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Urothelial cancer screening using urine cytology
• Urothelial cancer screening using urine tumor DNA test

Trial Overview The study is testing the effectiveness of a new urine tumor DNA test to screen for urothelial cancer in people with Lynch Syndrome. This will be compared to the standard urine cytology method to see if it can better detect cancer early.

How Is the Trial Designed?

Group I: Screening arm Experimental Treatment 2 Interventions

Invitation to participate in urothelial cancer screening and questionnaires

Urothelial cancer screening using urine tumor DNA test is already approved in European Union, United States for the following indications:

Approved in European Union as Urine Tumor DNA Test for:

• Screening for urothelial cancers in individuals with Lynch Syndrome

Approved in United States as Urine Tumor DNA Test for:

• Screening for urothelial cancers in individuals with Lynch Syndrome

Who Is Running the Clinical Trial?

Tampere University Hospital

Lead Sponsor

Trials

298

Recruited

404,000+

Tampere University

Collaborator

Trials

169

Recruited

2,335,000+

Published Research Related to This Trial

In a study of 44 bladder cancer patients, genetic alterations were found in 75% of tumor specimens, indicating a high prevalence of detectable changes associated with the disease.

The research demonstrated that 82% of microsatellite changes in tumors could be identified in urine, serum, and plasma samples, suggesting that these body fluids could serve as noninvasive tools for bladder cancer diagnosis and screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A possible noninvasive method for the detection of bladder cancer in patients: microsatellite analysis of free DNA in urine and blood. Utting, M., Werner, W., Müller, G., et al.[2019]

In a study of 164 patients with upper urinary tract urothelial carcinoma, the prevalence of Lynch syndrome was found to be at least 1.8%, highlighting the importance of screening for this genetic condition in these patients.

The study demonstrated that testing for microsatellite instability and mismatch repair protein expression is effective for identifying Lynch syndrome, with a concordance rate of 100% between the two testing methods, suggesting that universal tumor screening could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Lynch syndrome among patients with upper urinary tract carcinoma in a Japanese hospital-based population. Ito, T., Kono, K., Eguchi, H., et al.[2020]

In a study of 115 patients with upper tract urothelial carcinoma, 13.9% screened positive for potential Lynch syndrome, highlighting a significant risk for this genetic condition in these patients.

Of those screened, 5.2% were confirmed to have Lynch syndrome after further genetic analysis, indicating the importance of universal screening for better identification and management of this genetic risk in urological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma. Metcalfe, MJ., Petros, FG., Rao, P., et al.[2022]

In a study of 204 asymptomatic patients with Lynch syndrome, screening for urothelial carcinoma using urinalysis did not detect any cases of cancer, despite 9.3% showing microscopic hematuria that led to further evaluations.

Only 2.4% of patients were diagnosed with urothelial cancer during the study period, and all presented with symptoms outside of the screening intervals, suggesting that the current urinalysis-based screening approach may not be effective and could lead to unnecessary follow-up procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Urinalysis-Based Screening for Urothelial Carcinoma in Patients With Lynch Syndrome. Chouhan, H., Abbass, MA., Hrabe, JE., et al.[2021]

Urinary cell-free DNA can be used as a noninvasive method for detecting cancer mutations, specifically in patients with colorectal cancer.

This approach shows potential for monitoring tumor evolution and treatment failure, highlighting its clinical utility beyond just urological tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutational Analysis in Urinary Cell-Free DNA: KRAS in Colorectal Cancer. Molinari, C., Chiadini, E.[2021]

The Cxbladder test was instrumental in diagnosing high-grade upper tract urothelial carcinoma (UTUC) in a patient with Lynch syndrome, highlighting its potential as a valuable tool for monitoring high-risk patients.

After treatment with holmium laser ablation and BCG therapy, the patient showed negative results in urine cytology, UroVysion, and Cxbladder tests, indicating effective management of the UTUC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper Tract Urothelial Carcinoma in the Genetically Predisposed Patient: Role of Urinary Markers in Predicting Recurrence. Tan, WP., Tecle, N., Whelan, P., et al.[2020]

The UroSEEK test, which analyzes DNA from urine, successfully detected bladder cancer in 83% of patients who developed the disease, demonstrating its high efficacy as a non-invasive diagnostic tool.

When combined with traditional cytology, UroSEEK identified 95% of bladder cancer cases, and it was particularly effective in detecting low-grade tumors, where it found 67% of cases compared to none detected by cytology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. Springer, SU., Chen, CH., Rodriguez Pena, MDC., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41138669/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=0OrIQT_5uLCbron7-t0c3_Mi3GShe3lIBxkzLsYsA1A&fc=None&ff=20251029014421&v=2.18.0.post22+67771e2

Detection of urothelial carcinoma in Lynch syndrome using ... Lynch syndrome cancers are characterised by high levels of microsatellite instability (MSI/MSI-H). Here, we assess the feasibility of urine MSI ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06218433

Urothelial Cancer Screening in Individuals With Lynch ... In this clinical trial, we will employ urine tumor DNA (utDNA) to identify asymptomatic urothelial cancers in Lynch syndrome patients, and to investigate the ...

3. withpower.com withpower.com/trial/phase-syndrome-3-2023-c793d

Urine Tumor DNA Test for Lynch Syndrome This approach allows for early detection and monitoring of urothelial cancer in patients with Lynch Syndrome by analyzing DNA shed into the urine. Show more.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9782328/

Circulating tumor cells and cell-free tumor DNA analyses in ... Recent studies advocated universal screening by immunohistochemistry followed by microsatellite instability testing for early detection of the Lynch syndrome ...

5. mdpi.com mdpi.com/2072-6694/15/2/506

Relative Risk of Bladder and Kidney Cancer in Lynch ... Conclusion: Lynch syndrome is associated with a significant increase in the relative risk of kidney and bladder cancer. Clinicians should adopt a lower ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12447350/

Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome) Compared with selective testing for newly diagnosed CRC patients, universal Lynch syndrome screening has been found to be cost‐effective by most ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06218433?term=AREA%5BConditionSearch%5D(lynch%20syndrome)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=8

Urothelial Cancer Screening in Individuals With Lynch ... Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study) · Study Overview · Contacts and Locations.

8. e-juo.org e-juo.org/journal/view.php?number=551

Genetic Testing for Prostate Cancer, Urothelial ... Lynch syndrome is a genetic disorder that exhibits a low diagnostic rate when it manifests as urological tumors [25]. As a clinical precaution, ...