Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)

Urothelial Carcinoma Clinical Trial

Official title:

Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06218433
• Other study ID #: R22125
• Secondary ID: R22125
• Status: Recruiting
• Phase: N/A
• Start date: April 10, 2023
• Est. completion date: December 31, 2034

Study information

• Verified date: January 2024
• Source: Tampere University Hospital
• Contact: Jussi Nikkola, MD, PhD
• Phone: 03311611
• Email: jussi.nikkola[@]fimnet.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lynch syndrome (LS) is an inherited cancer predisposition syndrome caused by pathogenic germline variants in DNA mismatch repair (MMR) genes. New cancer screening and diagnostic tools are urgently needed to identify LS-related cancers early enough for curative treatment. Urothelial cancers (comprising bladder and upper tract urothelial tumors) are the third most common cancer after colorectal and endometrial cancers in individuals with LS. Up to one in four LS individuals will develop urothelial cancer during their lifetime, with the risk varying based on the defective MMR gene. In this clinical trial, we will employ urine tumor DNA (utDNA) to identify asymptomatic urothelial cancers in Lynch syndrome patients, and to investigate the potential benefits of urine tumor DNA based screening in this high-risk population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2034
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

Inclusion Criteria:

• Willing and able to provide informed consent

• Diagnosis of Lynch syndrome

• Age 50 - 75 years at study recruitment

Exclusion Criteria:

• Concurrent urothelial carcinoma

Related Conditions & MeSH terms

• Colorectal Neoplasms, Hereditary Nonpolyposis
• Lynch Syndrome
• Syndrome
• Urothelial Carcinoma

Intervention

Diagnostic Test:
• Urothelial cancer screening using urine tumor DNA test
Urine sample DNA is analyzed using a targeted sequencing panel encompassing the coding regions of 21 genes that are recurrently mutated in urothelial cancer
• Urothelial cancer screening using urine cytology (comparator)
Urine cytology sample

Locations

Country	Name	City	State
Canada	Vancouver Prostate Centre	Vancouver
Finland	Tampere University Hospital and Tampere University	Tampere

Sponsors (2)

Lead Sponsor	Collaborator
Tampere University Hospital	Tampere University

Countries where clinical trial is conducted

Canada,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sensitivity and specificity of urine cytology	Sensitivity and specificity of urine cytology for detecting urothelial cancer, using histologically verified cancers detected within 1 year of cytology as ground truth	At 1 year of follow-up
Other	Association of utDNA fraction with time to diagnosis of urothelial cancer	Association of utDNA fraction (quantified based on mutation allele fractions in urine DNA) with time to diagnosis of urothelial cancer	At 2, 5 and 10 years of follow-up
Other	Prevalence of somatic second hit in MMR genes	Prevalence of somatic second hit and additional somatic hits in mismatch repair genes (MSH2, MSH6, MLH1, PMS2) in Lynch syndrome patients diagnosed with urothelial cancer	At 1, 2, 5 and 10 years of follow-up
Other	Cost of utDNA screening	Analysis of the cost of utDNA screening, including cost per urothelial cancer found	At 1, 2, 5 and 10 years of follow-up
Primary	Sensitivity and specificity of positive utDNA for urothelial cancer within one year of follow-up	Sensitivity and specificity of positive utDNA for urothelial cancer, using histologically verified cancers detected within 1 year of the utDNA test as ground truth	At 1 years of follow-up
Secondary	Specificity of positive utDNA for urothelial cancer at the time of testing	Specificity of positive utDNA test for urothelial cancer, using histologically verified cancers detected in the cystoscopy and/or imaging performed due to positive utDNA test as the ground truth	After all patients with positive utDNA have been evaluated with cystoscopy and/or imaging
Secondary	Sensitivity and specificity of positive utDNA for urothelial cancer within multiple years of follow-up	Sensitivity and specificity of positive utDNA for urothelial cancer, using histologically verified cancers detected within 2, 5, and 10 years of the utDNA test as ground truth	At 2, 5, and 10 years of follow-up
Secondary	Overall survival	Overall survival in utDNA positive and negative patients	At 5 and 10 years of follow-up
Secondary	Urothelial cancer specific survival	Urothelial cancer specific survival survival in utDNA positive and negative patients	At 3, 5 and 10 years of follow-up
Secondary	Time to metastatic urothelial cancer	Time to metastatic urothelial cancer in utDNA positive and negative patients	At 5 and 10 years of follow-up
Secondary	Time to diagnosis of muscle invasive or high grade urothelial cancer	Time to diagnosis of muscle invasive or high grade urothelial cancer in utDNA positive and negative patients	At 2, 5 and 10 years of follow-up
Secondary	Time to diagnosis of urothelial cancer	Time to diagnosis of urothelial cancer in utDNA positive and negative patients	At 2, 5 and 10 years of follow-up
Secondary	TNM pathological stage of urothelial cancers	TNM pathological stage (American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC)) of urothelial cancers found in utDNA positive and negative patients	At 2, 5 and 10 years of follow-up
Secondary	Size of urothelial tumors	Maximum diameter of urothelial tumors found in utDNA positive and negative patients	At 2, 5 and 10 years of follow-up
Secondary	Urothelial cancer grade	The World Health Organization (WHO) 2004/2016 grading of urothelial cancers found in utDNA positive and negative patients	At 2, 5 and 10 years of follow-up