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

• ClinicalTrials.gov Identifier: NCT06218433
• Recruitment Status: Recruiting
• First Posted: January 23, 2024
• Last Update Posted: January 23, 2024
• Sponsor: Tampere University Hospital
• Collaborator: Tampere University
• Information provided by (Responsible Party): Tampere University Hospital

Tracking Information

• First Submitted Date: January 10, 2024
• First Posted Date: January 23, 2024
• Last Update Posted Date: January 23, 2024
• Actual Study Start Date: April 10, 2023
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 22, 2024)

Sensitivity and specificity of positive utDNA for urothelial cancer within one year of follow-up [ Time Frame: At 1 years 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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 22, 2024)

• Specificity of positive utDNA for urothelial cancer at the time of testing [ Time Frame: After all patients with positive utDNA have been evaluated with cystoscopy and/or imaging ]
  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
• Sensitivity and specificity of positive utDNA for urothelial cancer within multiple years of follow-up [ Time Frame: At 2, 5, and 10 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
• Overall survival [ Time Frame: At 5 and 10 years of follow-up ]
  Overall survival in utDNA positive and negative patients
• Urothelial cancer specific survival [ Time Frame: At 3, 5 and 10 years of follow-up ]
  Urothelial cancer specific survival survival in utDNA positive and negative patients
• Time to metastatic urothelial cancer [ Time Frame: At 5 and 10 years of follow-up ]
  Time to metastatic urothelial cancer in utDNA positive and negative patients
• Time to diagnosis of muscle invasive or high grade urothelial cancer [ Time Frame: At 2, 5 and 10 years of follow-up ]
  Time to diagnosis of muscle invasive or high grade urothelial cancer in utDNA positive and negative patients
• Time to diagnosis of urothelial cancer [ Time Frame: At 2, 5 and 10 years of follow-up ]
  Time to diagnosis of urothelial cancer in utDNA positive and negative patients
• TNM pathological stage of urothelial cancers [ Time Frame: At 2, 5 and 10 years of follow-up ]
  TNM pathological stage (American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC)) of urothelial cancers found in utDNA positive and negative patients
• Size of urothelial tumors [ Time Frame: At 2, 5 and 10 years of follow-up ]
  Maximum diameter of urothelial tumors found in utDNA positive and negative patients
• Urothelial cancer grade [ Time Frame: At 2, 5 and 10 years of follow-up ]
  The World Health Organization (WHO) 2004/2016 grading of urothelial cancers found in utDNA positive and negative patients

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 22, 2024)

• Sensitivity and specificity of urine cytology [ Time Frame: At 1 year of follow-up ]
  Sensitivity and specificity of urine cytology for detecting urothelial cancer, using histologically verified cancers detected within 1 year of cytology as ground truth
• Association of utDNA fraction with time to diagnosis of urothelial cancer [ Time Frame: At 2, 5 and 10 years of follow-up ]
  Association of utDNA fraction (quantified based on mutation allele fractions in urine DNA) with time to diagnosis of urothelial cancer
• Prevalence of somatic second hit in MMR genes [ Time Frame: At 1, 2, 5 and 10 years of follow-up ]
  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
• Cost of utDNA screening [ Time Frame: At 1, 2, 5 and 10 years of follow-up ]
  Analysis of the cost of utDNA screening, including cost per urothelial cancer found

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)
• Official Title: Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Screening

Condition

• Urothelial Carcinoma
• Lynch Syndrome

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
• Diagnostic Test: Urothelial cancer screening using urine cytology (comparator)
  Urine cytology sample

Study Arms

Experimental: Screening arm

Invitation to participate in urothelial cancer screening and questionnaires

Interventions:

• Diagnostic Test: Urothelial cancer screening using urine tumor DNA test
• Diagnostic Test: Urothelial cancer screening using urine cytology (comparator)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 22, 2024): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2034
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jussi Nikkola, MD, PhD; 03311611 ext +358; jussi.nikkola@fimnet.fi

• Listed Location Countries: Canada, Finland

Administrative Information

• NCT Number: NCT06218433
• Other Study ID Numbers: R22125; R22125 ( Other Identifier: Tampere University Hospital )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tampere University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Tampere University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Tampere University

Investigators

• Principal Investigator: Jussi Nikkola, MD, PhD; Tampere University Hospital

• PRS Account: Tampere University Hospital
• Verification Date: January 2024