PENK Methylation Test for Detecting Bladder Cancer

Study Overview
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Brief Summary
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The primary objective of this clinical trial is to determine the sensitivity and specificity of the EarlyTect® Bladder Cancer test for bladder cancer among patients with hematuria by comparing it to the results of cystoscopy examinations. The second objective is to compare the clinical performance of EarlyTect® Bladder Cancer test with a NMP22 test and urine cytology test with respect to bladder cancer. By histopathological examination, lesions identified during cystoscopy will be confirmed as malignant or non-malignant by histological examination.

Detailed Description
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Patients with hematuria who are scheduled for cystoscopy will be asked to collect a urine sample for EarlyTect® Bladder Cancer test and will undergo NMP22 and urine cytology tests. The participants will undergo a cystoscopy within 30 days of enrollment. For confirmation of the diagnosis and stage of the tumor, representative histopathology slides from TURBT (Transurethral Resection of Bladder Tumors) may be retrieved and examined by the central pathology laboratory.

Official Title
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A Multicenter, Single-blind, Prospective Clinical Trial to Evaluate the Clinical Performance of EarlyTect® Bladder Cancer Test in the Urine DNA for Detecting Bladder Cancer Among Hematuria Patients

Conditions
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Bladder Cancer, Hematuria; Benign

Intervention / Treatment
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* Diagnostic Test: EarlyTect® Bladder Cancer test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who agree to voluntarily sign an informed consent prior to the initiation of screening Adults aged ≥40 Subjects who have had gross or microscopic hematuria within the 3 months Subjects who had no history of bladder cancer and upper tract urothelial cancer Subjects who will undergo cystoscopy, NMP22 test, and urine cytology within 1 month after consent Exclusion Criteria: Individuals who do not agree to voluntarily sign an informed consent prior to the initiation of screening Subjects aged <40 years Subjects with a history of bladder cancer and upper tract urothelial cancer Female who are currently menstruating or who have had their last menstrual period within the last 3 days Subjects who have undergone invasive procedures in the urinary tract system within the last 3 months Subjects with suspected upper urothelial cancer lesions on ultrasound or CT scan Subjects who have previously received pelvic radiation therapy Subjects who have been diagnosed with other cancers and have received or are currently receiving chemotherapy or immunotherapy within 6 months Subjects who require treatment for an active urinary tract infection or vaginitis Subjects undergoing prostate cancer treatment or requiring a prostate biopsy Subject has any condition which, in the opinion of the investigator should preclude participation in the study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hematuria patients aged ≥40<br>Device: EarlyTect Bladder Cancer test, PENK methylation assay by LTE (Linear Target Enrichment)-qMSP (quantitative methylation-specific real time PCR) | Diagnostic Test: EarlyTect® Bladder Cancer test<br>* A highly accurate and sensitive real-time PCR employing Linear Target Enrichment and Quantitative Methylation-Specific PCR (LTE-qMSP) for measuring PENK methylation in urine DNA to detect bladder cancer in hematuria patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of the EarlyTect® Bladder Cancer test | Sensitivity and specificity of the EarlyTect® Bladder Cancer test for detecting bladder cancer (Stages Ta high-grade and T1-T4) in patients with hematuria compared to the cystoscopy examination, both in terms of detecting bladder cancer. The reference method is the cystoscopic procedure, and lesions will be assessed histopathologically. EarlyTect® Bladder Cancer test includes a measurement of PENK methylation and COL2A1 as a DNA control. PENK methylation in urine DNA will be assessed quantitatively by Linear Target Enrichment-coupled Quantitative Methylation-Specific PCR (LTE-qMSP) using the Real-time PCR method. The results will be dichotomized by the CT (cycle threshold) cutoff value as either positive or negative. Sensitivity = 100*(positive PENK methylation test/positive cystoscopy), Specificity = 100*(negative PENK methylation test/negative cystoscopy). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The performance of the EarlyTect® Bladder Cancer test | The performance of the EarlyTect® Bladder Cancer test in detecting Bladder cancer in hematuria patients will be compared with those of the NMP22 and urine cytology tests. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder cancer, Hematuria, Methylation biomarker, EarlyTect® Bladder Cancer test, Real-time PCR (LTE-qMSP), Urine