E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muscle-Invasive Bladder Cancer |
Cáncer de vejiga musculoinvasivo |
|
E.1.1.1 | Medical condition in easily understood language |
Bladder Cancer |
Cáncer de vejiga |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To compare the pCR rate of neoadjuvant nivolumab + NKTR-214 to Standard of Care (SOC, no neoadjuvant therapy) in all randomized participants - To compare the event-free survival (EFS) of neoadjuvant nivolumab + NKTR-214 followed by adjuvant nivolumab + NKTR-214 after radical cystectomy (RC) versus SOC (no neoadjuvant or adjuvant therapy) |
- Comparar la tasa de RCp de nivolumab + NKTR-214 neoadyuvantes con el tratamiento de referencia (TdR, sin tratamiento neoadyuvante) en todos los pacientes aleatorizados - Comparar la supervivencia libre de acontecimientos (SLA) de nivolumab + NKTR-214 neoadyuvantes seguido por nivolumab + NKTR-214 adyuvantes después de cistectomía radical (CR) frente al TdR (sin tratamiento neoadyuvante o adyuvante) |
|
E.2.2 | Secondary objectives of the trial |
- To compare the pCR rate of neoadjuvant nivolumab monotherapy to SOC (no neoadjuvant therapy) at the time of surgery - To compare the EFS of neoadjuvant nivolumab followed by adjuvant nivolumab versus SOC - To compare the overall survival (OS) of each experimental arm versus SOC - To assess safety and tolerability for each treatment arm |
- Comparar la tasa de RCp de nivolumab en monoterapia neoadyuvante con la obtenida con el TdR (sin tratamiento neoadyuvante) en el momento de la cirugía - Comparar la SLA con nivolumab neoadyuvante seguido por nivolumab adyuvante frente al TdR - Comparar la supervivencia global (SG) de cada brazo experimental frente al TdR - Evaluar la seguridad y la tolerabilidad de cada brazo de tratamiento |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Additional research is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements. This collection for additional research is intended to expand the translational Research and Development capability at BMS, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis and for the advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression, and response to treatment. Refer to protocol section 9.8.11 |
La investigación adicional es opcional para todos los participantes del estudio, excepto donde la retención y/o recogida está prohibida por legislación local, comités éticos o requerimientos institucionales. Esta recogida para la investigación adicional tiene como objetivo expandir la capacidad translacional de I+D en Bristol-Myers Squibb, y apoyará objetivos de investigación aún no definidos que fomentarán nuestra comprensión de la enfermedad y las opciones de tratamiento. También se podrá utilizar para apoyar las solicitudes de análisis de las autoridades sanitarias, y el avance del desarrollo farmacodiagnóstico para orientar mejor los fármacos hacia los pacientes adecuados. Esto también puede incluir la exploración genética/genómica dirigida a explorar las vías de la enfermedad, la progresión y la respuesta al tratamiento. Consultar la sección 9.8.11 del protocolo |
|
E.3 | Principal inclusion criteria |
- MIBC, clinical stage T2-T4a, N0, M0, diagnosed at transurethral resection of bladder tumor (TURBT) - Must be deemed eligible for RC by urologist, and must agree to undergo RC. For arms A and B, participants must agree to undergo RC after completion of neoadjuvant therapy. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Cisplatin-ineligible participants will be defined by any one of the following criteria: i) Impaired renal function (glomerular filtration rate [GFR] ≥ 30 but < 60 mL/min) ii) GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula) iii) Common Terminology Criteria for Adverse Events (CTCAE) version 5, ≥ Grade 2 hearing loss (assessed per local SOC). iv) CTCAE version 5, ≥ Grade 2 peripheral neuropathy. |
- CVMI, en estadio clínico T2-T4a, N0, M0, diagnosticados mediante resección transuretral del tumor de vejiga (RTUTV) - El paciente debe ser considerado elegible para CR por su urólogo y debe estar de acuerdo en someterse a CR. En los brazos A y B, los pacientes deben estar de acuerdo en someterse a CR después de finalizar el tratamiento neoadyuvante - Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1 - Se definirá a los pacientes inelegibles a cisplatino según uno de los siguientes criterios: i) Deterioro de la función renal (tasa de filtración glomerular [TFG] ≥ 30 pero < 60 ml/min) ii) La TFG debe evaluarse mediante medición directa (esto es, aclaramiento de creatinina) o, si no se dispone de ella, mediante cálculo a partir de creatinina sérica/plasmática (fórmula de Cockcroft-Gault) iii) Pérdida auditiva (evaluada según la manera de referencia) de grado ≥ 2 de los Criterios de Terminología Común de Acontecimientos Adversos (CTCAE) versión 5 iv) Neuropatía periférica de grado ≥ 2 de los CTCAE versión 5 |
|
E.4 | Principal exclusion criteria |
- Clinical evidence of pathologic lymph node (LN) or metastatic bladder cancer. - Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is not permitted. Prior Bacillus Calmette-Guerin (BCG) or other intravesicular treatment of non-muscle invasive bladder cancer (NMIBC) is permitted if completed at least 6 weeks prior to initiating study treatment. - Evidence of urothelial carcinoma (UC) in upper urinary tracts (ureters or renal pelvis) or history of previous MIBC or urothelial carcinoma not confined to the bladder. Other protocol defined inclusion/exclusion criteria could apply. |
- Pruebas clínicas de cáncer de vejiga con ganglios linfáticos (GL) patológicos o metastásico - No se permite tratamiento sistémico, radioterapia o cirugía previos para cáncer de vejiga aparte de TRUTV o biopsias. Se permite tratamiento previo con bacilo de Calmette-Guerin (BCG) u otro tratamiento intravesical del cáncer de vejiga no musculoinvasivo (CVNMI) si se terminó al menos 6 semanas antes de comenzar el tratamiento del estudio - Pruebas de carcinoma urotelial (CU) en las vías urinarias superiores (uréteres o pelvis renal) o antecedentes de CVMI o CU previo no limitado a la vejiga. Se pueden aplicar otros criterios de inclusión/exclusión definidos en el protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Pathologic complete response (pCR) rate of neoadjuvant nivolumab + NKTR-214 to Standard of Care (SOC) in all randomized participants - Event-free survival (EFS) of neoadjuvant nivolumab + NKTR-214 followed by adjuvant nivolumab + NKTR-214 after RC vs. SOC |
- Tasa de respuesta completa patológica (RCp) de nivolumab + NKTR-214 neoadyuvantes frente al tratamiento de referencia (TdR) en todos los pacientes aleatorizados - Supervivencia libre de acontecimientos (SLA) de nivolumab + NKTR-214 neoadyuvantes seguido de de nivolumab + NKTR-214 adyuvantes tras CR frente al TdR |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Approximately 36 months - Approximately 54 months |
- Aproximadamente 36 meses - Aproximadamente 54 meses |
|
E.5.2 | Secondary end point(s) |
- pCR rate of neoadjuvant nivolumab monotherapy to SOC at the time of surgery - EFS of neoadjuvant nivolumab followed by adjuvant nivolumab vs. SOC - Overall survival - Incidence of adverse events (AEs), of serious adverse events (SAEs), of AEs leading to discontinuation, of immune-mediated AEs (imAEs), of laboratory abnormalities |
- Tasa de RCp de nivolumab en monoterapia neoadyuvante frente al TdR en el momento de la cirugía - SLA de nivolumab neoadyuvante seguido de nivolumab adyuvante frente al TdR - Supervivencia global - Incidencia de acontecimientos adversos (AAs), de acontecimientos adversos graves (AAGs), de AAs que conducen a la suspensión, de AAs mediados por el sistema inmunitario, de anomalías de laboratorio |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Approximately 36 months - Approximately 54 months - Approximately 74 months - Up to 5 years |
- Aproximadamente 36 meses - Aproximadamente 54 meses - Aproximadamente 74 meses - Hasta 5 años |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Cistectomía radical |
Radical Cystectomy |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Greece |
Israel |
Italy |
Mexico |
Netherlands |
New Zealand |
Poland |
Russian Federation |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |