CxBladder Surveillance of Intermediate and High-Risk Bladder Cancer Patients

Study Overview
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Brief Summary
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Surveillance for recurrence of urothelial carcinoma (UC) requires frequent cystoscopy, which is invasive, expensive and time-consuming. An accurate urinary biomarker has the potential to reduce the number of cystoscopies required during post-treatment surveillance. This is a prospective single arm multi-center study using the diagnostic CxBladder test with subjects previously diagnosed positive with primary or recurrent UC and who are undergoing a schedule of investigative cystoscopies and treatment for the possible recurrence of urothelial carcinoma presenting to qualified sites. To test the pathway multiple consecutive urine samples will be collected during the course of surveillance and records review follow-up will also be completed.

Detailed Description
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This is a multi-site study recruiting subjects from Veterans Affairs and other medical centers. Subjects will be prospectively recruited to an observational study to validate the performance characteristics and clinical utility of CxBladder Monitor test (CxbM). The study will recruit intermediate and high-risk surveillance subjects, defined as per American Urological Association (AUA) / Society of Urologic Oncology (SUO) guidelines 2016 amendment 2020, previously diagnosed with urothelial carcinoma (UC).Eligible subjects will include those under surveillance for recurrence of UC. A strength of the proposed design is that subjects with primary or recurrence of UC can be recruited. This means, for some subjects, that there may be a range of surveillance visits prior to enrolment. A voided urine sample will be collected from each enrolled subject at each of 4 successive surveillance visits. Records review will occur 12, 24 and 48 months after the final urine sample is collected. The collected urine will be used for CxBladder testing and central urine cytology. The study will collect primary tumour tissue from the first (primary) tumour and also from the most recent recurrence, if any, in order to genotype each tumour using RNA or DNA markers indicative of an elevated risk of UC. CxBladder results will not be reported to patients or physicians. The objective of this study is to evaluate a new proposed pathway over a period of up to four visits where CxbM is alternated with cystoscopy at consecutive visits for intermediate and high-risk surveillance subjects. The new proposed pathway will be compared directly to standard of care. Analysis of data will include determining the proportion of subjects that are positive by surveillance cystoscopy (standard of care) following a negative diagnosis at the previous visit. Using the same dataset, analysis of data will include determining the proportion of subjects that are positive by surveillance cystoscopy (standard of care) following a negative CxBladder result at the previous visit. Analysis will include assessment of the theoretical possible reduction in cystoscopy procedure use associated with the new pathway. Sites are required to be competent in recruiting and completing required test request forms, Case Report Forms (CRF) and sample collection in a professional manner in accordance with good clinical practice (GCP).

Official Title
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An Observational Study of CxBladder Monitoring for Recurrence of Urothelial Carcinoma in Intermediate and High-Risk Patients

Conditions
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Urothelial Bladder Cancer

Intervention / Treatment
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* Diagnostic Test: CxBladder Monitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High and intermediate risk surveillance subjects with a previous confirmed diagnosis or recurrence of urothelial carcinoma Subjects must agree to 4 successive visits including urine sample collection at each of the study visits and records review follow-up Able to provide a voided urine sample (a sample from catheterization is not eligible) of the required minimum volume Able to give written consent Able and willing to comply with study requirements Aged 18 years or older Exclusion Criteria: Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterization, urethral dilation) in the 14 days before urine collection Total cystectomy of the bladder, subjects with neo-bladders or illeal conduits Previous muscle invasive bladder tumour (pT2 or greater) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Single arm - Patients undergoing surveillance for UC recurrence<br>Subjects previously diagnosed with UC and are undergoing a schedule of surveillance cystoscopies and treatment for the possible recurrence of UC will be recruited. Only intermediate and high-risk group, according to AUA /SUO risk categorisation for non-muscle invasive UC, will be eligible for this study. All subjects will undergo CxBladder urine diagnostic testing. | Diagnostic Test: CxBladder Monitor<br>* CxBladder Monitor (CxbM) is a high sensitivity and negative predictive value (NPV) urinary biomarker test to rule-out subjects at low risk of bladder cancer monitoring for recurrence of disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the proposed pathway failure rate versus the standard of care failure rate. | The failure rate will be measured as the proportion of all subjects experiencing a failure event. A failure event for the proposed pathway is defined as any visit where standard of care cystoscopy is confirmed as positive for a given visit when Cxbladder Monitor was negative at the immediate previous visit. A failure event for the standard of care is defined as any visit where standard of care cystoscopy is confirmed as positive for a given visit when standard of care cystoscopy was negative at the immediate previous visit. (The gold standard for determination of a confirmed clinical diagnosis is cystoscopy and any other procedures relating to the visit with confirmation by pathology following review of a biopsy specimen). | 12 months |