Non-Muscle Invasive Bladder Neoplasms
Conditions
Brief summary
The purpose of this study is to compare disease free survival (DFS) in participants with recurrence of papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC) within 1 year of last dose of Bacillus Calmette-Guérin (BCG) therapy and who refused or are unfit for Radical Cystectomy (RC), receiving TAR-200 versus investigator's choice of single agent intravesical chemotherapy.
Interventions
DRUGTAR-200
Participants will receive TAR-200 intravesically.
DRUGMitomycin C
Participants will receive MMC intravesically.
DRUGGemcitabine
Participants will receive gemcitabine intravesically.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis by local pathology (within 90 days of documented informed consent) of recurrent, papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC) \[defined as high-grade Ta or any T1, no carcinoma in situ (CIS)\] * Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial (transitional cell histology) predominance. However, neuroendocrine, and small cell variants will be excluded * Participants must be ineligible for or have elected not to undergo Radical Cystectomy (RC) * Have an Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0, 1, or 2
Exclusion criteria
* Presence of CIS at any point from time of diagnosis of papillary-only HR-NMIBC recurrence to randomization. Additionally, presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, N+, and/or M+) * Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200. Participants with tumors involving the prostatic urethra in men will be excluded * A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 milliliters (\>4000 mL) * Indwelling catheters are not permitted; however, intermittent catheterization is acceptable * Previous treatment with TAR-200
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | Up to 6 years 7 months | DFS will be measured as the time from randomization to the time of the first recurrence of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) \[high grade (HG) Ta, any T1 or carcinoma in situ (CIS)\], progression, or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival (RFS) | Up to 6 years 7 months | RFS will be measured as the time from randomization to the time of the first recurrence of HR-NMIBC (HG Ta, any T1 or CIS), or death due to any cause, whichever occurs first. |
| Time to Next Intervention (TTNI) | Up to 6 years 7 months | TTNI will be measured as the time from randomization to the time of next intervention (localized or systemic) for the treatment of bladder cancer. |
| Time to Disease Worsening (TTDW) | Up to 6 years 7 months | TTDW is measured as the time from randomization to cystectomy, systemic therapy, or radiation therapy (treatments of disease worsening). |
| Time to Progression (TTP) | Up to 6 years 7 months | TTP will be measured as the time from randomization to the time of first documented evidence of disease progression (that is, progression to muscle-invasive bladder cancer \[MIBC\] \[T greater than or equal to {\>=} 2\], lymph node disease \[N+\], or distant disease \[M+\]), or death due to disease progression, whichever occurs first. |
| Overall Survival (OS) | Up to 6 years 7 months | OS is defined as the time from randomization to death, due to any cause. |
| DFS Rate at 12 and 24 Months | At 12 and 24 months | DFS rate that is percentage of participants with DFS at 12 and 24 months will be reported. |
| Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE) | Up to 6 years 7 months | Number of participants with AEs by severity grade as assessed by CTCAE version 5 will be reported. Grade refers to the severity of AE as follows: Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5- Death related to adverse event. |
| Number of Participants With Change from Baseline in Laboratory Abnormalities | Up to 6 years 7 months | Number of participants with change from baseline in laboratory abnormalities (including hematology, clinical chemistry and routine urinalysis) will be reported. |
| Number of Participants With Change from Baseline in Vital Signs Abnormalities | Up to 6 years 7 months | Number of participants with change from baseline in vital signs including temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic and diastolic) (supine) will be reported. |
| Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) - C30 Scores | Up to 5 years | EORTC QLQ-C30 is a 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much). |
| Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores | Up to 5 years | EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with NMIBC. The questionnaire is designed to supplement the QLQ-C30 and incorporates 6 multi-item scales (urinary symptoms, malaise, future worries, bloating and flatulence, sexual function and male sexual problems) and 5 single items (intravesical treatment issues, sexual intimacy, worries about risk of contaminating partner, sexual enjoyment, and female sexual problems). Ratings for each item range from 1 (not at all) to 4 (very much). |
| Proportion of Participants With Meaningful Change in EORTC QLQ-C30 and EORTC QLQ-NMIBC24 Scores | Up to 5 years | Proportion of participants with meaningful change in EORTC QLQ-C30 and EORTC QLQ-NMIBC24 scores will be reported. |
Countries
Argentina, Belgium, Brazil, China, France, Germany, Italy, Japan, Poland, Romania, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical trial
Janssen Research & Development, LLC
Outcome results
None listed