CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer

Bladder Cancer Clinical Trial

— CISTO  

Official title:

CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03933826
• Other study ID #: SITE00001017
• Secondary ID: PCS-2017C3-9380R
• Status: Active, not recruiting
• Start date: July 9, 2019
• Est. completion date: March 31, 2025

Study information

• Verified date: January 2024
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Bladder cancer is the most common urinary tract cancer and the 5th most common cancer in the US (1). Yet bladder cancer research is underfunded relative to other common cancers. As a result, bladder cancer care is prone to evidence gaps that produce decision uncertainty for both patients and clinicians. The Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) for Bladder Cancer Study has the potential to fill these critical evidence gaps, change care pathways for the management of NMIBC (non-muscle-invasive bladder cancer), and provide for personalized, patient-centered care. The purpose of CISTO is to conduct a large prospective study that directly compares the impact of medical management versus bladder removal in recurrent high-grade NMIBC patients with BCG (Bacillus Calmette-Guerin) failure on clinical outcomes and patient and caregiver experience using standardized patient-reported outcomes (PROs).

Description:

Most bladder cancer patients (74%) present with NMIBC where the cancer is limited to the lining or support layer of the bladder. High-grade NMIBC is treated initially with endoscopic resection and intravesical immunotherapy, followed by bladder instillations of BCG. Most patients with high-risk, high-grade NMIBC are able to retain their bladders and avoid more invasive treatments. However, 24-61% of patients will have their cancers recur within 12 months of treatment with BCG (BCG failures), and they have limited treatment options. National guidelines recommend consideration between two alternatives: additional medical management and radical cystectomy (removal of the bladder). Selecting between these options involves weighing the risk of progression of bladder cancer and loss of a window of potential cure versus the risk of morbidity and loss of quality of life (QOL) with bladder removal. This complex decision-making engages patients and their caregivers, who may be impacted by the urinary, sexual, and bowel dysfunctions that can occur with NMIBC treatment. The investigators will evaluate this research question on a large scale in real world practice settings including academic and community-based practices and examine patient-centered outcomes. The investigators have engaged stakeholders with diverse perspectives relevant to this research question, including patients, caregivers, national patient advocacy organizations, national medical specialty organizations, guideline developers, health care payers, and industry. By engaging broad expertise relevant to this research question, the investigators will ensure that the study results will help NMIBC patients whose cancer recurs after BCG treatment make more informed decisions that improve the health outcomes that are important to them. CISTO is an observational study that will not affect the treatment that patients chose. Patient surveys will occur at study entry and at follow-up assessments for up to four years. There will also be a qualitative sub-study that will include interviews of approximately 50 patients and 25 caregivers recruited from the observational cohort study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 572
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

Patient Eligibility, Inclusion Criteria:

1. Adult 18 years of age or older; and

2. Presenting with high-grade NMIBC established by anatomic pathology as tumor stage

classification Tis, Ta, or T1, and with:

1. Pathology documentation from any hospital/clinic/medical center, and

2. More than 50% urothelial carcinoma component in the specimen

3. History of high-grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1; and

4. Attempted or received induction BCG (at least 3 out of 6 instillations) at any point in time; and

5. In the previous 12 months, received at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment.

Patient Eligibility, Exclusion Criteria:

1. Any plasmacytoid or small cell (neuroendocrine) component in the pathology (past or current presentation);

2. Previous history of cystectomy or radiation therapy for bladder cancer;

3. Previous history of muscle-invasive bladder cancer or metastatic bladder cancer;

4. Any history of upper tract urothelial carcinoma;

5. Incarcerated in a detention facility or in police custody (patients wearing a monitoring device can be enrolled) at baseline/screening;

6. Contraindication to radical cystectomy (e.g., ASA of 4, patient not considered a radical cystectomy candidate due to comorbidity);

7. Contraindication to medical therapy (i.e., intolerant of all medical therapies);

8. Unable to provide written informed consent in English;

9. Unable to be contacted for research surveys;

10. Planning to participate in a Phase I or Phase II interventional clinical trial for NMIBC (unless in the control/comparator arm of a Phase II trial) or any blinded interventional trial for NMIBC.

Related Conditions & MeSH terms

• Bladder Cancer
• Cancer of the Bladder, Recurrent
• Non-muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Locations

Country	Name	City	State
United States	Michigan Medicine Rogel Cancer Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Johns Hopkins University, School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Spectrum Health	Grand Rapids	Michigan
United States	Chesapeake Urology Research Associates	Hanover	Maryland
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCLA	Los Angeles	California
United States	USC/Norris Comprehensive CA Center	Los Angeles	California
United States	Asante Rogue Regional Medical Center	Medford	Oregon
United States	LSU Healthcare Network - Multi Specialty Clinic	Metairie	Louisiana
United States	University of Miami	Miami	Florida
United States	Carolina Urologic Research Center, LLC	Myrtle Beach	South Carolina
United States	Urology Associates, P.C.	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	Comprehensive Urology -- A Division of Michigan Healthcare Professionals	Royal Oak	Michigan
United States	University of Utah	Salt Lake City	Utah
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30)	The primary evaluation of patient-reported quality of life, as measured by the EORTC QLQ-C30 at 12 months, will be conducted using targeted maximum likelihood estimation (TMLE) analysis. All of the subscales and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated.	12 months after completion of the patient baseline assessment
Secondary	Patient-reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30)	The evaluation of the effect of treatment choice on the trajectory of patient-reported quality of life, as measured by the EORTC QLQ-C30 at up to 48 months, will be conducted using both mixed effects and generalized estimating equations (GEE) longitudinal models.	Up to 48 months after completion of the patient baseline assessment
Secondary	Patient self-reported urinary function as measured by the Bladder Cancer Index	The evaluation of the effect of treatment choice on patient-reported urinary function, as measured by the Bladder Cancer Index (BCI) at 12 months, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of urinary function at up to 48 months as measured by the BCI will be conducted using both mixed effects and GEE longitudinal models. The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score and two subscale scores (function and bother) are constructed. Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient self-reported sexual function as measured by the Bladder Cancer Index	The evaluation of the effect of treatment choice on patient-reported sexual function, as measured by the BCI at 12 months, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of sexual function at up to 48 months as measured by the BCI will be conducted using both mixed effects and GEE longitudinal models.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient self-reported NMIBC treatment preferences	Patients' generic quality of life as measured in quality adjusted life years (QALY) by a series of time tradeoff (TTO) questions at 12 months post-enrollment will be modeled as a function of patient preferences, as measured by additional TTO items measuring QALY for bladder cancer-related health states, while controlling for patients' baseline quality of life, demographic and clinical characteristics using beta regression, stratified by treatment arm.	12 months after completion of the patient baseline assessment
Secondary	Patient self-reported decisional regret	Patient-reported decisional regret will be measured using three items with 5-point Likert response scales which have been validated in a previous study of prostate cancer patients. These three items will be summed to yield a score from 0 to 12, with higher scores indicating greater regret. The evaluation of the effect of treatment choice on patient-reported decisional regret at 12 months will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient-reported decisional regret at up to 48 months will be conducted using both mixed effects and GEE longitudinal models.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient self-reported financial distress as measured by the Comprehensive Score for Financial Toxicity (COST)	The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by COST at 12-months, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of patient financial distress at up to 48 months will be conducted using both mixed effects and GEE longitudinal models. The COST questionnaire consists of 11 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating greater financial toxicity. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient self-reported healthcare utilization as measured by hospital and urology clinic days	The evaluation of the effect of treatment choice on healthcare utilization, as measured by 12-month hospital and urology clinic days, will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on the trajectory of patient healthcare utilization at up to 48 months will be conducted using both mixed effects and GEE longitudinal models.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient self-reported return to work/normal activities	The evaluation of the effect of treatment choice on patient self-reported return to work/normal activities will be conducted using TMLE analysis.	12 months after completion of the patient baseline assessment
Secondary	Patient disease-free survival	The evaluation of the effect of treatment choice on patient 12-month disease-free survival will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient disease-free survival at up to 48 months will be conducted using TMLE-based survival analysis.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient metastasis-free survival	The evaluation of the effect of treatment choice on patient 12-month metastasis-free survival will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient metastasis-free survival at up to 48 months will be conducted using TMLE-based survival analysis.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient progression to muscle-invasive bladder cancer	The evaluation of the effect of treatment choice on patient 12-month progression to muscle-invasive bladder cancer will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient progression to muscle-invasive bladder cancer at up to 48 months will be conducted using TMLE-based survival analysis.	12 months after completion of the patient baseline assessment and up to 48 months
Secondary	Patient bladder cancer-specific survival	The evaluation of the effect of treatment choice on patient 12-month bladder cancer-specific survival will be conducted using TMLE analysis. The evaluation of the effect of treatment choice on patient bladder cancer-specific survival at up to 48 months will be conducted using TMLE-based survival analysis.	12 months after completion of the patient baseline assessment and up to 48 months