Replacing Invasive Cystoscopy With Urine Testing for Non-muscle Invasive Bladder Cancer Surveillance

Non-muscle-invasive Bladder Cancer Clinical Trial

— ReplaceCysto  

Official title:

Replacing Invasive Cystoscopy With Urine Testing for Non-muscle Invasive Bladder Cancer Surveillance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05796375
• Other study ID #: 1732756
• Secondary ID: R37CA2759161R37C
• Status: Recruiting
• Phase: N/A
• Start date: November 17, 2023
• Est. completion date: May 30, 2029

Study information

• Verified date: May 2024
• Source: White River Junction Veterans Affairs Medical Center
• Contact: Florian R Schroeck, MD, MS
• Phone: 802-295-9363
• Email: florian.schroeck[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research is to determine whether bladder cancer monitoring can be improved by replacing some cystoscopy procedures with urine testing. Specifically, this study examines whether there are any differences in urinary symptoms, discomfort, number of invasive procedures, anxiety, complications, cancer recurrence or cancer progression when some cystoscopy procedures are replaced with urine testing.

Description:

This is a multi-site randomized phase 2 trial including 240 patients with early-stage bladder cancer, in which patients will be randomized 1:1:1 to programmatic surveillance with the Xpert bladder cancer urine test, the Bladder EpiCheck urine test, or frequent cystoscopy. The primary outcome will be urinary quality of life measured 1 to 3 days after surveillance.

This study will have three groups, also called "arms": (1) Frequent Cystoscopy Arm, (2) Xpert Urine Test Arm, and (3) Epicheck Urine Test Arm. The aim of Frequent Cystoscopy is to detect any cancer that might have come back within the bladder by frequently inspecting the bladder. Those in the cystoscopy arm will have a cystoscopy procedure at specified time points for two years. The goal of the Xpert Urine Test arm is to detect any cancer that might have come back within the bladder, while decreasing the number of invasive cystoscopy procedures. Those in the Xpert arm will have a Xpert urine test and a check-up with a medical doctor at 6 months and 18 months, and have a cystoscopy procedure at 12 months and 24 months. The aim of the EpiCheck Urine Test arm is to detect any cancer that might have come back within the bladder, while decreasing the number of invasive cystoscopy procedures. Those in the EpiCheck Urine Test arm will have an Epicheck urine test and a check-up with a medical doctor at 6 months and 18 months and will have a cystoscopy procedure at 12 months and 24 months. The study performance period is 24 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: May 30, 2029
• Est. primary completion date: May 28, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Aged 18 years or older

2. History of low grade intermediate-risk non-muscle invasive bladder cancer, defined as most recent pathology report showing any of the following:

• multifocal low grade non-invasive urothelial carcinoma of any size

• solitary low grade non-invasive urothelial carcinoma greater than 3cm in size

• recurrent low grade non-invasive urothelial carcinoma

3. Stated willingness to comply with all study procedures and availability for the duration of the study

4. No evidence for recurrence at cystoscopy =4 months after most recent tumor resection

5. Ability to consent in English or Spanish

Exclusion Criteria:

1. History of total cystectomy of the bladder.

2. History of urinary diversion (e.g., neo-bladder, colon pouch, or ileal conduit).

3. History of muscle-invasive bladder tumor.

4. Pregnancy or lactation.

5. History of urothelial carcinoma of the ureter or renal pelvis status post endoscopic treatment or with evidence of recurrent upper tract disease (inclusion allowed if status post nephroureterectomy and recurrence free at time of inclusion)

6. Anatomic constraints making cystoscopy impossible (e.g., history of urethrectomy, obliterated urethra secondary to stricture).

7. Inability to provide a voided urine sample.

Related Conditions & MeSH terms

• Non-muscle-invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Procedure:
• Cystoscopy
Cystoscopy entails direct inspection of the bladder via a cystoscope that is inserted into a patient's urethra.

Diagnostic Test:
• Bladder EpiCheck urine test
The Bladder EpiCheck is a laboratory-developed test for early-stage non-muscle invasive bladder cancer. The Bladder EpiCheck test is a DNA methylation test that is run on DNA extracted from cell pellet from centrifuged urine according to Standardized Operating Procedures. The test has internal controls and a dedicated software to ensure required quality assurance processes and prompt reporting of results.
• Xpert Bladder Cancer Monitor urine test
A 4.5 ml sample of voided urine is added to Xpert® Urine Transport Reagent, mixed, and then 4ml of treated urine are transferred to the Sample Chamber of the cartridge. In the cartridge, cells in the urine sample are captured on a filter and lysed by sonication. The released nucleic acid is eluted, mixed with dry RT-PCR reagents, and the solution is transferred to the reaction tube for RT-PCR and detection.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	UT Southwestern Medical Center	Dallas	Texas
United States	White River Junction Veterans Healthcare System	White River Junction	Vermont

Sponsors (4)

Lead Sponsor	Collaborator
White River Junction Veterans Affairs Medical Center	Medical University of South Carolina, National Cancer Institute (NCI), University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (4)

Koo K, Zubkoff L, Sirovich BE, Goodney PP, Robertson DJ, Seigne JD, Schroeck FR. The Burden of Cystoscopic Bladder Cancer Surveillance: Anxiety, Discomfort, and Patient Preferences for Decision Making. Urology. 2017 Oct;108:122-128. doi: 10.1016/j.urology.2017.07.016. Epub 2017 Jul 21. — View Citation

Laukhtina E, Shim SR, Mori K, D'Andrea D, Soria F, Rajwa P, Mostafaei H, Comperat E, Cimadamore A, Moschini M, Teoh JY, Enikeev D, Xylinas E, Lotan Y, Palou J, Gontero P, Babjuk M, Witjes JA, Kamat AM, Roupret M, Shariat SF, Pradere B; European Association of Urology-Young Academic Urologists (EAU-YAU): Urothelial Carcinoma Working Group. Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis. Eur Urol Oncol. 2021 Dec;4(6):927-942. doi: 10.1016/j.euo.2021.10.003. Epub 2021 Nov 6. Erratum In: Eur Urol Oncol. 2022 Jan 19;: — View Citation

Sayyid RK, Sayyid AK, Klaassen Z, Hersey K, Goldberg H, Perlis N, Ahmad A, Leao R, Chandrasekar T, Fadaak K, Madi R, Terris MK, Finelli A, Hamilton RJ, Kulkarni GS, Zlotta AR, Fleshner NE. Replacing surveillance cystoscopy with urinary biomarkers in followup of patients with non-muscle-invasive bladder cancer: Patients' and urologic oncologists' perspectives. Can Urol Assoc J. 2018 May;12(5):E210-E218. doi: 10.5489/cuaj.4922. Epub 2018 Feb 6. — View Citation

Schroeck FR, Lynch KE, Li Z, MacKenzie TA, Han DS, Seigne JD, Robertson DJ, Sirovich B, Goodney PP. The impact of frequent cystoscopy on surgical care and cancer outcomes among patients with low-risk, non-muscle-invasive bladder cancer. Cancer. 2019 Sep 15;125(18):3147-3154. doi: 10.1002/cncr.32185. Epub 2019 May 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of Life Questionnaire-Non-Muscle Invasive Bladder Cancer 24 (EORTC QLQ-NMIBC24)	Measuring change from baseline. Score range: 0-100. Lower score indicates higher quality of life.	Assessed at 3, 6, 12, 18, and 24 months.