The purpose of study is to compare bladder intact-event free survival (BI-EFS) in participants receiving TAR-200 in combination with intravenous (IV) cetrelimab versus concurrent chemoradiotherapy.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Ineligible for or have elected not to undergo radical cystectomy
All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (\<) 2 prior to randomization
Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
Thyroid function tests are within the normal range per investigator assessment (or stable on hormone supplementation). Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal test results
Adequate bone marrow, liver, and renal function: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (\>=) 1,500/cubic millimeters (mm\^3); Platelet count \>=80,000/mm\^3; Hemoglobin \>=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (\<=) 1.5 \* upper limit of normal (ULN) or direct bilirubin \<= ULN for participants with total bilirubin levels greater than (\>)1.5\*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin \< 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\* institutional ULN); 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

Criterios de exclusión

Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study
Must not have diffuse CIS 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
Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging (chest, abdomen, and pelvis must be performed using Computed tomography \[CT\] or Magnetic resonance imaging \[MRI\]) within 42 days prior to randomization
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
Evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has healed prior to randomization

Intervenciones

biological

Cetrelimab

Participants will receive intravenous Cetrelimab.

drug

TAR-200

Participants will receive intravesical TAR-200.

drug

Cisplatin

Participants will receive cisplatin intravenously.

drug

Gemcitabine

Participants will receive gemcitabine intravenously.

radiation

Conventional radiation therapy

Participants will receive conventional radiation therapy for bladder (64 gy).

radiation

Hypo-fractioned radiation therapy

Participants will receive hypo-fractioned radiation therapy for bladder (55 gy).

Ubicaciones

Fundacion Intecnus

Bariloche, Argentina

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

Asociacion de Beneficencia Hospital Sirio Libanes

Buenos Aires, Argentina

Instituto Medico Especializado Alexander Fleming

Buenos Aires, Argentina

Centro de Urologia (CDU)

Ciudad Automoma Buenos Aires, Argentina

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Córdoba, Argentina

Centro Urologico Profesor Bengio

Córdoba, Argentina

Sanatorio Allende Cerro

Córdoba, Argentina

Centro Oncologico Riojano Integral (Cori)

La Rioja, Argentina

Centro de Investigacion Pergamino SA

Pergamino, Argentina

CEDIC Centro de Investigaciones Clinicas

Viedma, Argentina

A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder Who Are Not Receiving Radical Cystectomy

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Cetrelimab

TAR-200

Cisplatin

Gemcitabine

Conventional radiation therapy

Hypo-fractioned radiation therapy

Ubicaciones

Fundacion Intecnus

Hospital Italiano de Buenos Aires

Asociacion de Beneficencia Hospital Sirio Libanes

Instituto Medico Especializado Alexander Fleming

Centro de Urologia (CDU)

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Centro Urologico Profesor Bengio

Sanatorio Allende Cerro

Centro Oncologico Riojano Integral (Cori)

Centro de Investigacion Pergamino SA

CEDIC Centro de Investigaciones Clinicas

Patrocinadores