Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10046720 Term: Urothelial carcinoma bladder stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classif
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =18 years at the time of informed consent. 2.Histologically proven, cT2-T4a N0, M0 urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes (e.g. squamous cell carcinoma) are allowed if urothelial (transitional cell) differentiation is predominant. However, the presence of small cell or neuroendocrine variants will make a participant ineligible. 3. Ineligible for or have elected not to undergo radical cystectomy. 4. All adverse events associated with any prior surgery and/or intravesical therapy must haveresolved to CTCAE version 5.0 Grade 1.5xULN (except participants with Gilbert's Syndrome, who must have a total bilirubin <3.0 mg/dL), ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5x institutional ULN c. Renal function: Creatinine clearance =30 mL/min using the Cockcroft-Gault formula. 24-hour creatinine clearance test will also be accepted for estimating renal function in situations where Cockcroft-Gault formula is not a good predictor of estimating adequate renal function. Note: If cisplatin is chosen as the radio-sensitizing agent, creatinine clearance must be =50 mL/min. 8. Contraceptive use by participants should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. Investigators will advise participants on the options for banking of sperm and ova, for reproductive conservation. a. A participant must be either of the following: i. Not of childbearing potential ii. Of childbearing potential and practicing true abstinence, or have a sole partner who is vasectomized, or practicing at least 1 highly effective user independent method of contraception. Participant must agree to continue the above throughout the study and for 6 months after the last dose of study treatment. Note: If a participant becomes of childbearing potential after start of the study, the participant must comply with point (ii), as described above. A participant must also agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study treatment, and not be breastfeeding and not planning to become pregnant during the study and for at least 6 months after the last dose of study treatment. Participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility. Investigators will advise participants on the options for banking of ova for reproductive conservation. b. Participants must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any
Exclusion criteria
Exclusion criteria: 1. Active malignancies other than the disease being treated under study. 2. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. 3. Must not have diffuse carcinoma in situ based on cystoscopy and biopsy. Diffuse, or multi-focal, CIS is defined as the presence of at least 4 distinct CIS lesions in the bladder at the time of the Screening re-TURBT. 4. Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging within 42 days prior to randomization. 5. 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. 6. Evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has healed prior to randomization. 7. Bladder post-void residual volume >350 mL at screening after second voided urine. 8. History of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000-mL. 9. Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to randomization. 10. Received intervening serial intravesical chemotherapy or immunotherapy from the time of pre-screening (diagnostic) or screening (completion) cystoscopy/Transurethral Resection of Bladder Tumor to starting study treatment. Peri-operative intravesical chemotherapy prior to study treatment is allowed per institutional guidelines. 11. Prior therapy with an anti-programmed cell death 1, anti-PD-ligand agent, or with an agent directed to another co-inhibitory T-cell receptor. 12. Participants with a history of Grade =3 toxic effects when using anti-TNF or anti-IL-6 agents. 13. Received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent. Participants with a history of prior pelvic radiotherapy are excluded 14. An active autoimmune disease that has required systemic treatment in the past 2 years are excluded. 15. Received a live virus vaccine within 30 days prior to he initiation of study treatment. Inactivated (non-live or non-replicating) vaccines approved or authorized for emergency use (eg, COVID 19) by local health authorities are allowed. 16. Active infection requiring systemic IV therapy within 14 days prior to randomization. 18. A pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted if it does not interfere with placement or retention of TAR-200 in the bladder. Participants with unilateral hydronephrosis are permitted; however, participants with bilateral hydronephrosis are excluded. 19. Indwelling urinary catheters are not permitted; however, intermittent catheterization is acceptable. 20. Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses >10 mg/day of prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF-alpha blockers. Use of immunosuppressive medications for the management of immune related adverse events, infusion related reactions, or in participants with contrast allergies is acceptable. Use of inhaled, topical, and intranasal corticosteroids are permitted. 21. Must not have clinically significant liver disease t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare bladder intact event-free survival (BI-EFS) in participants receiving TAR-200 in combination with cetrelimab versus concurrent chemoradiotherapy.;Secondary Objective: - To compare metastasis-free survival (MFS) in participants receiving TAR-200 in combination with IV cetrelimab versus concurrent chemoradiotherapy - To compare the Overall Survival (OS) in participants receiving TAR-200 in combination with IV cetrelimab versus concurrent chemoradiotherapy - To compare the Overall Response Rate (ORR)(Complete Response [CR] or Partial Response [PR]) in both treatment arms at Week 18. - To assess the safety and tolerability of participants receiving TAR-200 in combination with IV cetrelimab versus concurrent chemoradiotherapy ;Primary end point(s): Time from randomization to the first BI-EFS event, including histologically proven presence of muscle-invasive bladder cancer (MIBC), clinical evidence of nodal or metastatic disease (as assessed by RECIST 1.1 criteria), radical cystectomy (RC), or death due to any cause.;Timepoint(s) of evaluation of this end point: 18 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time from randomization to first radiologic (as assessed by RECIST 1.1 criteria) evidence of metastatic disease or death due to any cause. - Time from randomization to death. - The ORR is defined as the proportion of participants who achieve a CR or PR - Frequency and grade of adverse events (AEs) (according to Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) and according to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE). NCI PROCTCAE assessments will be done for all urinary and all gastrointestinal items in the NCI PRO-CTCAE item library. Laboratory abnormalities: CTCAE grades and NCI PRO-CTCAE grades comparing baseline to the worst post-baseline value.;Timepoint(s) of evaluation of this end point: - Duration of trial | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, European Union, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, South Africa, Spain, Taiwan, Türkiye, Ukraine, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed