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A Study of TAR-200 Versus Intravesical Chemotherapy in Participants With Recurrent High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC) After Bacillus Calmette-Guérin (BCG)

Phase 3
Recruiting
Conditions
Non-Muscle Invasive Bladder Neoplasms
Interventions
Registration Number
NCT06211764
Lead Sponsor
Janssen Research & Development, LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
250
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group B: Mitomycin C (MMC) or GemcitabineMitomycin CParticipants will receive either single agent intravesical MMC or gemcitabine every week during an induction phase and every 4 weeks during a maintenance phase.
Group B: Mitomycin C (MMC) or GemcitabineGemcitabineParticipants will receive either single agent intravesical MMC or gemcitabine every week during an induction phase and every 4 weeks during a maintenance phase.
Group A: TAR-200TAR-200Participants will receive intravesical TAR-200 every 3 weeks during an induction phase and every 12 weeks during a maintenance phase.
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Number of Participants With Change from Baseline in Vital Signs AbnormalitiesUp 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.

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 \[N+\], 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.

Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) - C30 ScoresUp 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).

DFS Rate at 12 and 24 MonthsAt 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.

Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 ScoresUp 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 ScoresUp to 5 years

Proportion of participants with meaningful change in EORTC QLQ-C30 and EORTC QLQ-NMIBC24 scores will be reported.

Number of Participants With Change from Baseline in Laboratory AbnormalitiesUp 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.

Trial Locations

Locations (122)

Arkansas Urology

🇺🇸

Little Rock, Arkansas, United States

Genesis Research LLC

🇺🇸

Torrance, California, United States

USC Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

University of California Irvine Medical Center

🇺🇸

Orange, California, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Colorado Clinical Research

🇺🇸

Lakewood, Colorado, United States

Florida Urology Partners

🇺🇸

Riverview, Florida, United States

UroPartners

🇺🇸

Chicago Ridge, Illinois, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Urology of Indiana

🇺🇸

Carmel, Indiana, United States

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Arkansas Urology
🇺🇸Little Rock, Arkansas, United States

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