Clinical trial NCT03933826: CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer
Official title: CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Bladder Cancer
Cancer of the Bladder, Recurrent
Non-muscle Invasive Bladder Cancer
Keywords: 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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2019-05-01
Enrollment: 572
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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. There will also be a qualitative sub-study that will include interviews of 50 patients and 25 caregivers recruited from the observational cohort study.

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).

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.

Eligibility 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, 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.

Primary outcomes:
measure: 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)
timeFrame: 12 months after completion of the patient baseline assessment
Secondary outcomes:
measure: 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)
timeFrame: Up to 48 months after completion of the patient baseline assessment
measure: Patient self-reported urinary function as measured by the Bladder Cancer Index
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient self-reported sexual function as measured by the Bladder Cancer Index
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient self-reported NMIBC treatment preferences
timeFrame: 12 months after completion of the patient baseline assessment
measure: Patient self-reported decisional regret
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient self-reported financial distress as measured by the Comprehensive Score for Financial Toxicity (COST)
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient self-reported healthcare utilization as measured by hospital and urology clinic days
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient self-reported return to work/normal activities
timeFrame: 12 months after completion of the patient baseline assessment
measure: Patient disease-free survival
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient metastasis-free survival
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient progression to muscle-invasive bladder cancer
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
measure: Patient bladder cancer-specific survival
timeFrame: 12 months after completion of the patient baseline assessment and up to 48 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive CA Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Metairie
country: United States
facility: LSU Healthcare Network - Multi Specialty Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University, School of Medicine
state: Maryland
city: Hanover
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine Rogel Cancer Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Royal Oak
country: United States
facility: Comprehensive Urology -- A Division of Michigan Healthcare Professionals
state: Michigan
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Medford
country: United States
facility: Asante Rogue Regional Medical Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: John L Gore, MD
role: PRINCIPAL_INVESTIGATOR
References: