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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.

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

Clinicaltrials.gov identifier NCT03933826

Recruitment Status Recruiting

First Posted May 1, 2019

Last update posted May 3, 2021

Study Description

Brief 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).

  • Condition or Disease:Bladder Cancer
    Cancer of the Bladder, Recurrent
    Non-muscle Invasive Bladder Cancer
  • Intervention/Treatment:
  • Phase: N/A
Detailed 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.

Study Design
  • Study Type: Observational
  • Estimated Enrollment: 900 participants
  • Observational Model: Cohort
  • Time Perspective: Prospective
  • Official Title: CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer
  • Actual Study Start Date: July 2019
  • Estimated Primary Completion Date: October 2023
  • Estimated Study Completion Date: January 2024
Outcome Measures
  • Primary Outcome Measures: 1. 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) [ Time Frame: 12 months after completion of the patient baseline assessment ]
    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.
  • Secondary Outcome Measures: 1. 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) [ Time Frame: Up to 48 months after completion of the patient baseline assessment ]
    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.
  • 2. Patient self-reported urinary function as measured by the Bladder Cancer Index [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 3. Patient self-reported sexual function as measured by the Bladder Cancer Index [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 4. Patient self-reported NMIBC treatment preferences [ Time Frame: 12 months after completion of the patient baseline assessment ]
    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.
  • 5. Patient self-reported decisional regret [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 6. Patient self-reported financial distress as measured by the Comprehensive Score for Financial Toxicity (COST) [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 7. Patient self-reported healthcare utilization as measured by hospital and urology clinic days [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 8. Patient self-reported return to work/normal activities [ Time Frame: 12 months after completion of the patient baseline assessment ]
    The evaluation of the effect of treatment choice on patient self-reported return to work/normal activities will be conducted using TMLE analysis.
  • 9. Patient disease-free survival [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 10. Patient metastasis-free survival [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
  • 11. Patient progression to muscle-invasive bladder cancer [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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. Patient bladder cancer-specific survival [ Time Frame: 12 months after completion of the patient baseline assessment and up to 48 months ]
    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.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers:
  • Sampling Method: Non-Probability Sample
  • Study Population: Patients with a diagnosis of recurrent high-grade NMIBC that failed first-line BCG and who are considering second-line treatment will be approached for participation in this observational study in addition to their caregivers. Enrollment at each site will aim for a 2:1 ratio of participants selecting medical management to radical cystectomy in order to ensure adequate enrollment of radical cystectomy patients. The goal is to have 300 recurrent high-grade NMIBC patients enrolled in the radical cystectomy arm. There will also be a qualitative sub-study that will include interviews of 50 patients and 25 caregivers recruited from the observational cohort study.
Criteria

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);

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 or any blinded interventional trial for NMIBC.

Contacts and Locations
Contacts

Contact: Kristin Follmer 206-685-8708 cistopm@uw.edu

Contact: Erika Wolff, PhD 206-221-3174 ewolff2@uw.edu

Locations
Show 27 Study Locations
Sponsors and Collaborators

University of Washington

Patient-Centered Outcomes Research Institute

Investigators

Principal Investigator: John L Gore, MD University of Washington

More Information
  • Responsible Party: University of Washington
  • ClinicalTrials.gov Identifier: NCT03933826 History of Changes
  • Other Study ID Numbers: STUDY00006845, PCS-2017C3-9380, RG1121143, NCI-2020-06082
  • First Posted: May 1, 2019 Key Record Dates
  • Last Update Posted: May 3, 2021
  • Last Verified: April 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: De-identified study data will be shared according to the PCORI policy for data management and data sharing.
  • Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP)
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by University of Washington: pragmatic trial
    Bacillus Calmette-Guerin (BCG)
    urinary bladder neoplasms
    urogenital neoplasms
    radical cystectomy
    neoplasms by site
    neoplasms
    urinary bladder disease
    immunologic factors
    caregivers
    physiological effects of drugs
    immunologic adjuvants
    urologic diseases
  • Additional relevant MeSH terms: Urinary Bladder Neoplasms