The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06218433
Recruitment Status : Recruiting
First Posted : January 23, 2024
Last Update Posted : January 23, 2024
Sponsor:
Collaborator:
Tampere University
Information provided by (Responsible Party):
Tampere University Hospital

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Lynch Syndrome Diagnostic Test: Urothelial cancer screening using urine tumor DNA test Diagnostic Test: Urothelial cancer screening using urine cytology (comparator) Not Applicable

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)
Actual Study Start Date : April 10, 2023
Estimated Primary Completion Date : April 30, 2025
Estimated Study Completion Date : December 31, 2034

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Screening arm
Invitation to participate in urothelial cancer screening and questionnaires
 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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Overall survival [ Time Frame: At 5 and 10 years of follow-up ]
    Overall survival in utDNA positive and negative patients

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. 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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06218433


Contacts
Layout table for location contacts
Contact: Jussi Nikkola, MD, PhD 03311611 ext +358 jussi.nikkola@fimnet.fi

Locations
Layout table for location information
Canada
Vancouver Prostate Centre Not yet recruiting
Vancouver, Canada
Contact: Peter Black         
Principal Investigator: Peter Black         
Finland
Tampere University Hospital and Tampere University Recruiting
Tampere, Finland
Contact: Jussi Nikkola         
Principal Investigator: Jussi Nikkola         
Principal Investigator: Matti Annala         
Principal Investigator: Jukka-Pekka Mecklin         
Principal Investigator: Toni Seppälä         
Sponsors and Collaborators
Tampere University Hospital
Tampere University
Investigators
Layout table for investigator information
Principal Investigator: Jussi Nikkola, MD, PhD Tampere University Hospital
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Tampere University Hospital
ClinicalTrials.gov Identifier: NCT06218433    
Other Study ID Numbers: R22125
R22125 ( Other Identifier: Tampere University Hospital )
First Posted: January 23, 2024    Key Record Dates
Last Update Posted: January 23, 2024
Last Verified: January 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tampere University Hospital:
Lynch syndrome
Hereditary cancer syndrome
Screening
Urothelial neoplasms
Bladder neoplasms
 Upper tract urothelial neoplasms
Urogenital diseases
Liquid biopsies
Urine tumor DNA
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms, Hereditary Nonpolyposis
Syndrome
Disease
Pathologic Processes
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
 Neoplasms by Site
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases