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| ID | Type | Description | Link |
|---|---|---|---|
| R22125 | Other Identifier | Tampere University Hospital |
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| Name | Class |
|---|---|
| Tampere University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Screening arm | Experimental | Invitation to participate in urothelial cancer screening and questionnaires |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Urothelial cancer screening using urine tumor DNA test | Diagnostic 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Association of utDNA fraction with time to diagnosis of urothelial cancer |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jussi Nikkola, MD, PhD | Contact | 03311611 | +358 | jussi.nikkola@fimnet.fi |
| Name | Affiliation | Role |
|---|---|---|
| Jussi Nikkola, MD, PhD | Tampere University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vancouver Prostate Centre | Recruiting | Vancouver | Canada |
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| Urothelial cancer screening using urine cytology (comparator) | Diagnostic Test | Urine cytology sample |
|
| 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 |
| Overall survival | Overall survival in utDNA positive and negative patients | At 5 and 10 years of follow-up |
| Urothelial cancer specific survival | Urothelial cancer specific survival survival in utDNA positive and negative patients | At 3, 5 and 10 years of follow-up |
| Time to metastatic urothelial cancer | Time to metastatic urothelial cancer in utDNA positive and negative patients | At 5 and 10 years of follow-up |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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 |
| 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 |
| 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 |
| Tampere University Hospital and Tampere University | Recruiting | Tampere | Finland |
|
| ID | Term |
|---|---|
| D002295 | Carcinoma, Transitional Cell |
| D003123 | Colorectal Neoplasms, Hereditary Nonpolyposis |
| D009386 | Neoplastic Syndromes, Hereditary |
| D001749 | Urinary Bladder Neoplasms |
| D000091642 | Urogenital Diseases |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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