Clinical trial NCT02676180: Detecting Bladder Cancer Using the UroMark Test.
Official title: A Prospective Observational Study to Determine the Negative Predictive Value of UroMark to Rule Out the Presence of Bladder Cancer in Patients With Haematuria.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bladder Cancer
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2016-02-08
Enrollment: 3700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with visible and non-visible haematuria (blood in urine) will be enrolled. About 10% of cases with haematuria will be found to have bladder cancer. For the majority of cases (60.5%), no cause is found. Other causes include stone disease (3.6%), benign prostate conditions (20-30%), renal disease (9.8%) infection (13%) and renal/prostate cancer (1%). The DETECT I study will determine if the UroMark test can be used to rule out bladder cancer in cases referred for investigation of haematuria.

Brief summary: DETECT I is a prospective multicentre observational diagnostic study to assess the performance of the UroMark assay to rule out bladder cancer in patients with haematuria. The study will recruit consecutive patients attending haematuria clinics as well as patients referred to urology outpatient clinics for investigation of haematuria. Consenting patients will be provided with a urine sample collection kit and asked to provide a urine sample. An additional urine sample for control assay testing will be provided after the clinic attendance.

Detailed description: Transitional cell carcinoma (TCC) of the urinary bladder is responsible for \>12,000 new cases of cancer and \>5,000 deaths per year in England and Wales. Most bladder cancers are non-muscle invasive bladder cancer (NMIBC) and do not invade deeply at presentation, but 80% of tumours recur within 3 years. For muscle invasive bladder cancer (MIBC), the 5 year survival is around 50%. Cystoscopy is the standard test for detection of bladder cancer along with imaging to assess the upper tracts and the common presenting symptom is haematuria. Cystoscopy is an invasive procedure and results in urinary infection in up to 5% of cases. Cystoscopy is performed under local anaesthetic and patients are required to attend hospital clinics for the test. About one in 10 patients who are investigated for haematuria will be found to have bladder cancer. Frequently, patients are not referred for investigation of haematuria at the time of first presentation and there is a delay in diagnosis of the disease. The early detection of bladder cancer by means of a non-invasive tumour marker test would impact on the management of the disease. There is an unmet need for a simple, non-invasive, highly sensitive and specific method for detecting bladder cancer.

This study will determine the accuracy of UroMark a high-throughput multiplex PCR test to detect bladder cancer in DNA from urine. The study will address the unmet clinical need to improve detection of bladder cancer. The rationale for the trial is based on proof of concept studies which provide compelling evidence that a panel of methylation markers can be applied to detect bladder cancer with high sensitivity and specificity. It will be also be possible to collect and store fractions of urine for assessment of other DNA related biomarkers as well as non-DNA assays for example cellular proteins, soluble biomarkers in urine supernatant and RNA transcripts in sediment cells. In this study we will compare the UroMark assay with established assays including urinary cytology, FISH as well as developing assays such as MCM5. In this proposal excess urine will be stored for these studies.

Eligibility criteria: Inclusion Criteria:

* Participants must be over 18 years of age.
* Participants undergoing investigation for visible and non-visible haematuria.
* Able to give informed written consent.

Exclusion Criteria:

* Unwilling to have standard haematuria investigations.
* Unable to give informed consent.

Primary outcomes:
measure: Negative predictive value (NPV) of the UroMark test.
timeFrame: Baseline
Secondary outcomes:
measure: Negative predictive value (NPV) of control assay (FDA approved urinary marker (UroVision)).
timeFrame: Baseline
measure: Negative predictive value (NPV) against imaging (ultrasound/CT)
timeFrame: Baseline
measure: Negative predictive value (NPV) against combination of UroMark and imaging.
timeFrame: Baseline
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: UCLH
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
Study officials:
affiliation: UCL
name: John Kelly, FRCS (urol)
role: PRINCIPAL_INVESTIGATOR
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