Bladder Cancer
Conditions
Interventions
TAR-200 Cohort 1: TAR-200 and Cetrelimab: TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Da
Sponsors
Fujikawa Ei
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed diagnosis of persistent or recurrent high-risk, non-muscle invasive bladder cancer (HR-NMIBC) (carcinoma in situ [CIS]; Tumour in situ[Tis]), with or without papillary disease (T1, high-grade Ta)or papillary disease only (high-grade Ta or any T1 and absence of CIS), within 12 months of completion of the (last dose) of adequate Bacillus Calmette-Guerin (BCG) therapy , in participants who have received adequate BCG. Mixed histology tumours are allowed if urothelial differentiation (transitional cell histology) is predominant (example, less than (<) 20 percent (%) variant histologic subtype). However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. For participants with lamina propria invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor (TURBT), muscularis propria must be present in order to rule out Muscle Invasive Bladder Cancer (MIBC) - All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS acceptable for participants eligible for Cohorts 1, 2, and 3 only) and documented in the electronic case report form (eCRF) at screening cystoscopy. For participants with papillary disease only (Cohort 4), local urine cytology at screening must be negative or atypical (for High-Grade Urothelial Carcinoma [HGUC]) - Participants must be ineligible for or have elected not to undergo radical cystectomy - BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or at least 2 of 6 doses of a second induction course - Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
Exclusion criteria
Exclusion criteria: - Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV - Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephrouretrectomy more than 24 months prior to randomization - Participants with an active, known or suspected autoimmune disease. Participants with autoimmune disorders not requiring systemic treatment (example, skin conditions such as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll - Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test and participants with history of hepatitis B infection with positive hepatitis B surface antigen (HBsAg) antibody and undetectable PCR are allowed) - Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort 1, 2, and 3:Overall Complete Clinical Response (CR) Rate Up to 5 years Overall CR rate, is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point. Cohort 4:Disease-free Survival (DFS) Up to 5 years DFS will be measured as the time from the date of first dose of study treatment to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| -Cohort 1, 2, and 3:Duration of Response (DOR):Up to 5 years DOR is defined from the date of first CR achieved to the date of first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR. -Overall Survival (OS):Up to 5 years OS, defined as the time from the date of first dose of study treatment to death; if a participant has not died at the time of analysis, the participant will be censored at the date last known alive. -Cohort 1 and 2: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma:Up to Week 21 Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed. -Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies:Predose, up to 3 years Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis. -Number of Participants with Anti-cetrelimab Antibodies:Predose, up to 3 years Number of participants with anti-cetrelimab antibodies will be reported. -Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores:Baseline, up to 3 years and 4 months EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 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:Baseline, up to 3 years and 4 months EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30 and incorpo | — |
Countries
Australia, Canada, France, Germany, Greece, Italy, Japan, South Korea, United States
Contacts
Public ContactMedical Information Center
Janssen Pharmaceutical K.K.
Outcome results
None listed