STRATA: Safe Testing of Risk for AsymptomaTic MicrohematuriA

• ClinicalTrials.gov Identifier: NCT03988309
• Recruitment Status: Recruiting
• First Posted: June 17, 2019
• Last Update Posted: September 22, 2022
• Sponsor: Pacific Edge Limited
• Information provided by (Responsible Party): Pacific Edge Limited

Study Description

Brief Summary:

To evaluate the clinical utility associated with the integration of Cxbladder into the evaluation of subjects presenting with hematuria for evaluation of urothelial carcinoma (UC) without compromising detection of UC.

Condition or disease	Intervention/treatment	Phase
Hematuria; Urothelial Carcinoma	Diagnostic Test: Cxbladder	Not Applicable

Detailed Description:

Randomised two arm pragmatic clinical study to be conducted at multiple sites in US and Canada. The trial will recruit hematuria subjects, presenting to qualified sites (academic, community), who are being evaluated for urothelial carcinoma (UC). Up to 100 consecutive eligible subjects will be recruited per site.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Use of a Multiplexed Molecular Biomarker Test Cxbladder, in Real World Decision Making to Provide Clinical Utility Using a Randomized Design ("STRATA Study")
• Actual Study Start Date: September 11, 2019
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Test, subjects categorised as "low risk" or "Not low risk"; A clinical risk factor nomogram risk classification will be used in this study. The nomogram categorizes subjects as either "low risk" or "not low risk" categories. "Low risk" subjects satisfy all conditions and "not low risk" satisfies at least one of the conditions.The Cxbladder Triage test result will be provided to physicians for all "low risk" subjects on the test arm. If a "low risk" subject has a Cxbladder Triage negative test result then the indication is to rule out the subject without further assessment. The decision to rule-out or further evaluate is solely that of the physician and subject. If the "low risk" subjects are not Cxbladder Triage negative then a Cxbladder Detect test result will also be provided. The indication is further evaluation as per standard of care. Subjects categorised as "not low risk" will be evaluated as per standard of care. Note that Cxbladder test results will be available for eventual analysis for these subjects.	Diagnostic Test: Cxbladder; The Cxbladder Triage test result will be provided to physicians for all "low risk" subjects on the test arm. If a "low risk" subject has a Cxbladder Triage negative test result then the indication is to rule out the subject without further assessment. The decision to rule-out or further evaluate is solely that of the physician and subject. If the "low risk" subjects are not Cxbladder Triage negative then a Cxbladder Detect test result will also be provided. The indication is further evaluation as per standard of care. "Not low risk" patients will be evaluated as per standard of care.
No Intervention: Control; Subjects on the control arm will be on standard of care. Trial nomogram clinical risk factor categorization for control arm subjects will not be provided to the physician (but appropriate information will be collected on the CRF to enable sub-group analysis) No Cxbladder test results will be provided for control arm subjects. Note that Cxbladder test results will be available for eventual analysis for these subjects.

Outcome Measures

Primary Outcome Measures :

1. To measure the change in cystoscopy procedure use count between control and test arms when Cxbladder is used in the evaluation [ Time Frame: The outcome measure will be assessed by 6 months after trial completion. ]
   To evaluate the increase in utility as defined by the reduction in cystoscopy procedure count when Cxbladder is used in the evaluation. The comparison will be made when comparing test and control arms on a per subject basis. The gold standard for determination of a confirmed clinical diagnosis is cystoscopy confirmed by pathology, plus imaging or any follow-up investigations relating to the visit.

Secondary Outcome Measures :

1. To measure the change in total procedure use (and the invasive procedure sub-group) count between control and test arms when Cxbladder is used in the evaluation. [ Time Frame: The outcome measure will be assessed by 6 months after trial completion. ]
   To evaluate the increase in utility as defined by the reduction in total procedures (and the invasive procedures subgroup) count when Cxbladder is used in the evaluation. The comparison will be made when comparing test and control arms on a per subject basis.
2. To measure the proportion of subjects who were ruled out on the test arm when Cxbladder is used in the evaluation [ Time Frame: The outcome measure will be assessed by 6 months after trial completion. ]
   To quantify the 'rule-out' percentage (proportion ruled out from further evaluation by the physician) when Cxbladder is used in the evaluation.
3. To measure the number of subjects who were incorrectly diagnosed associated with the integration of Cxbladder into the evaluation of subjects (or sub-cohorts on test and control arms) presenting with hematuria for evaluation of UC [ Time Frame: The outcome measure will be assessed by 6 months after trial completion. ]
   To quantify the false negative rate (the percentage of the negative fraction incorrectly diagnosed) associated with the integration of Cxbladder into the evaluation of subjects (or sub-cohorts on test and control arms) presenting with hematuria for evaluation of UC
4. Proportion of subjects (and sub-groups within test and control arms) with bladder cancer who are correctly identified as having cancer (true positives) and no cancer (true negatives) by the Cxbladder test. [ Time Frame: The outcome measure will be assessed by 6 months after trial completion. ]
   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 referred for evaluation of hematuria.
5. To compare the total score of the anxiety and pain level associated with cystoscopy vs Cxbladder by using Patient Result Outcome questionnaire and WIWI(was it worthy it) [ Time Frame: The outcome measure will be assessed by 6 months after trial completion. ]
   Subjects will have Patient Reported Outcomes at enrollment for all subjects on the test arm to set a baseline and post cystoscopy for all subjects on the test arm. For all of the PROMIS short forms we will report PROMIS T-scores. For both measures, the raw score will be converted to a T-score which rescales the raw score into a standardized score that ranges from 0 to 100 with a mean of 50 and a standard deviation of 10. Anxiety level has four questions with five scales of answers. Pain level has three questions with five scales of answers. WIWI has 6 questions on the three scales to describe answers.
6. Comparison of the Cxbladder test's sensitivity, specificity, PPV and NPV with that of Cytology. [ Time Frame: 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. 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.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patient is undergoing investigation of recent confirmed hematuria, as defined by the AUA/SUFU Guideline (Barocas DA, Boorjian SA, Alvarez RD et al. Microhematuria: AUA/SUFU guideline, J Urol 2020; 204:778) (by either flexible or rigid cystoscopy/TURBT), including hematuria subjects 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 or pelvic radiotherapy. Prior history prostate or renal cell carcinoma within the last 5 years.
• Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection,
• Known current pregnancy

Contacts and Locations

Contacts

Contact: Yair Lotan, MD; 2146458764; yair.lotan@utsouthwestern.edu

Locations

United States, California

Institute of Urology, USC Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90089

Contact: Ileana Aldana 323-865-0702 ileana.aldana@med.usc.edu

Principal Investigator: Sumeet Bhanvadia

United States, Illinois

Accellacare; Recruiting

Chicago, Illinois, United States, 60515

Contact: Janeal James janeal.james@accellacare.com

Principal Investigator: Amit Patel

United States, Minnesota

University of Minnesota, Department of Urology; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Tracy M Daye-Groves tmgroves@umn.edu

Principal Investigator: Christopher Warlick

United States, Pennsylvania

Division of urology, Penn State Milton S Hershey Medical Center; Recruiting

Hershey, Pennsylvania, United States, 17033-0850

Contact: Kathy Lehman 717-531-5930 klehman3@pennstatehealth.psu.edu

Principal Investigator: Jay Raman

United States, South Carolina

Carolina Urologic Research Center; Recruiting

Myrtle Beach, South Carolina, United States, 29572

Contact: Jessica Richardson, RN 843-449-1010 ext 261 jrichardson@curcmb.com

Principal Investigator: Neal Shore, MD

United States, Tennessee

Department of Urology,Vanderbilt University; Recruiting

Nashville, Tennessee, United States, 37232

Contact: Pamela Steele 615-343-2120 pamela.steele@vumc.org

Principal Investigator: Kristin Scarpato

United States, Texas

UT Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Jess Ramos 214-645-8764 jess.ramos@UTSouthwestern.edu

Principal Investigator: Yair Lotan, MD

UTHSA - Mays Cancer Center; Recruiting

San Antonio, Texas, United States, 78229

Contact: Karl F Norton 210-450-9630 nortonk1@uthscsa.edu

Principal Investigator: Robert Svatek, MD

Canada, British Columbia

The prostate centre- Diamond Health care centre; Recruiting

Vancouver, British Columbia, Canada, V5Z1M9

Contact: Sarah Charlesworth 604-875-4111 ext 69308 scharlesworth@prostatecentre.com

Principal Investigator: Peter Black

Canada, Ontario

London Health Sciences Centre Victoria Hospital; Recruiting

London, Ontario, Canada, N6A5W9

Contact: Kaydee Connors 519-685-8455 ext 56366 kaydee.connors@lhsc.on.ca

Principal Investigator: Jonathan Izawa

Sponsors and Collaborators

Pacific Edge Limited

Investigators

• Study Chair: Tony Lough, PhD; Pacific Edge Pty Ltd

More Information

• Responsible Party: Pacific Edge Limited
• ClinicalTrials.gov Identifier: NCT03988309
• Other Study ID Numbers: CXB/2019/US
• First Posted: June 17, 2019
• Last Update Posted: September 22, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hematuria; Urination Disorders; Urologic Diseases; Hemorrhage; Pathologic Processes