Efficacy and Utility of Cxbladder Tests in Hematuria Patients

An Observational Study of Efficacy and Utility of Cxbladder Tests in the Identification of Low vs High Risk Patients and the Detection of Urothelial Carcinoma in Patients Presenting With Hematuria

Prospective observational study to validate the performance characteristics and clinical utility of Cxbladder tests in a Veterans Affairs cohort.

Study Overview

• Status: Active, not recruiting
• Conditions: Urothelial Carcinoma; Hematuria
• Intervention / Treatment: Diagnostic test: Cxbladder

Detailed Description

Non-invasive, voided urine sample used for both Cxbladder molecular tests, voided urine sample may be used for standard of care testing. Retrospective analysis of data after study completion ensures a de-phasing of study sample analysis from clinical decision making; patient treatment and management.

The study aims to sequentially recruit up to 1000 patients presenting for assessment of hematuria (microscopic or macroscopic) by cystoscopy across multiple Veterans Affairs sites

• Study Type: Observational
• Enrollment (Actual): 684

Contacts and Locations

• Study Contact: Name: Michael Risk; Phone Number: (612) 467-5601; Email: mcrisk@umn.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • Veterans Medical Research Foundation
  • Florida
    • Bay Pines, Florida, United States, 33744-8200
      • Bay Pines Veterans Affairs
    • Miami, Florida, United States, 33125
      • South Florida Veterans Affairs
    • Tampa, Florida, United States, 33612-4745
      • James A Haley Veterans' Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • NWIHCS-Omaha VA Medical Center
  • New York
    • New York, New York, United States, 10468-3904
      • James J. Peters VAMC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma City VA Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Medical University of South Carolina
  • Vermont
    • White River Junction, Vermont, United States, 05009
      • White River Junction VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted with all hematuria patients who present to an outpatient clinic to undergo clinical assessment including cystoscopy and who fulfil study requirements. Consented eligible patients will attend their scheduled clinic visit and undergo all standard tests as clinically indicated.

Description

Inclusion Criteria:

• Patient is undergoing investigation of recent confirmed hematuria (by either flexible or rigid cystoscopy/TURBT), including hematuria patients referred due to suspicious/positive imaging, in order to determine the presence of urothelial carcinoma.
• Able to provide a voided urine sample 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 history of bladder malignancy, prostate or renal cell carcinoma
• Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection
• Previous alkylating based chemotherapy
• Known Pregnancy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

patients with hematuria undergoing investigation for UC; Patients will be recruited from those presenting with hematuria and undergoing investigative cystoscopy for the determination of possible urothelial carcinoma. This includes patients referred via imaging or from other departments for assessment of hematuria. Microscopic hematuria is defined as > 3 red blood cells per high-powered microscopy field for a properly collected urine sample.

Diagnostic test: Cxbladder; The Cxbladder Detect test, developed by Pacific Edge Ltd (O'Sullivan 2012; Holyoake 2008; National Health Committee 2015b) is a molecular diagnostic test, which consists of five mRNA transcripts measured in a small volume of urine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with bladder cancer who are correctly identified as having cancer (true positives) and no cancer (true negatives) by the Cxbladder test.	The Cxbladder test results will be compared to that of cystoscopy, which is the gold standard method for diagnosing urothelial cancer; the true positive and true negative rates will be measured, along with the false positive and false negative rates of the test. The results will be reported as sensitivity and specificity of the Cxbladder test for detecting urothelial cancer in patients with hematuria	The outcome measure will be assessed by 6 months after trial completion.
Probability that patients identified as having cancer and no cancer by the Cxbladder test truly have cancer (positive predictive value; PPV), and truly have no cancer (negative predictive value; NPV) respectively.	The Cxbladder test results will be compared to that of cystoscopy, which is the gold standard method for diagnosing urothelial cancer; the true positive and true negative rates will be measured, along with the false positive and false negative rates of the test. The results will be reported as sensitivity and specificity of the Cxbladder test for detecting urothelial cancer in patients with recurrent disease.	Time Frame: The outcome measure will be assessed by 6 months after trial completion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the Cxbladder test's sensitivity, specificity, PPV and NPV with that of Cytology.	Performance characteristics (sensitivity, specificity, PPV and NPV) of the Cxbladder test for detecting recurring urothelial cancer will be compared to urine cytology, in addition to the gold standard test (cystoscopy). All comparator tests will be carried out on the same voided urine sample used for Cxbladder tests.	The outcome measure will be assessed by 6 months after trial completion.
To compare the theoretical clinical outcome of patients tested using Cxbladder tests	To compare the theoretical clinical outcome of patients tested using Cxbladder tests in combination (Triage followed by Detect and / or Resolve) before investigative cystoscopy with evaluation by (positive, negative or suspicious) cystoscopy alone to establish the true proportion requiring cystoscopy, thereby determining the potential of Cxbladder to reduce or adjudicate the cystoscopy burden of hematuria patients and/or sub cohorts under clinical evaluation in a hospital urology clinic setting.	The outcome measure will be assessed by 6 months after trial completion.
To compare the theoretical clinical outcome of patients tested using Cxbladder signatures before investigative cystoscopy with evaluation by cystoscopy alone to establish the true proportion requiring cystoscopy.	To compare the theoretical clinical outcome of patients tested using Cxbladder signatures before investigative cystoscopy with evaluation by (positive, negative or suspicious) cystoscopy alone to establish the true proportion requiring cystoscopy, thereby determining the potential of Cxbladder to reduce or adjudicate the cystoscopy burden of hematuria patients and/or sub cohorts under clinical evaluation in a hospital urology clinic setting.	The outcome measure will be assessed by 6 months after trial completion.
Performance characteristics of Cxbladder Triage and Cxbladder Detect compared with results generated at other clinical sites	To evaluate the performance characteristics of Cxbladder Triage and Cxbladder Detect compared with results generated at other clinical sites, and to the results of the pulished clinical studies by O'Sullivan et al in 2012 and Kavalieris et al in 2015	The outcome measure will be assessed by 6 months after trial completion.

Collaborators and Investigators

• Sponsor: Pacific Edge Limited
• Investigators: Study Chair: Tony Lough, PhD, Pacific Edge Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2019
• Primary Completion (Actual): January 18, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: June 27, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Diseases; Neoplasms, Glandular and Epithelial; Hemorrhage; Urination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma; Carcinoma, Transitional Cell; Hematuria
• Other Study ID Numbers: CXB/2019/VA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No