E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Renal Cell Carcinoma with Intermediate- or Poor-Risk Factors |
Carcinoma de células renales avanzado con factores de riesgo intermedio o alto |
|
E.1.1.1 | Medical condition in easily understood language |
Renal Cell Carcinoma |
Carcinoma de células renales |
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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 | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
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 PFS using RECIST 1.1 of nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants - To compare the ORR using RECIST 1.1 of nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants |
- Comparar la SLP, usando los RECIST 1.1, de nivolumab en combinación con ipilimumab y nivolumab y placebo en todos los participantes aleatorizados - Comparar la TRO, usando los RECIST 1.1, de nivolumab en combinación con ipilimumab y nivolumab y placebo en todos los participantes aleatorizados. |
|
E.2.2 | Secondary objectives of the trial |
- To compare the OS of nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants - To evaluate additional efficacy measures in all randomized participants. - To estimate the incidence of AEs of nivolumab combined with ipilimumab and nivolumab and placebo in all treated participants - To investigate whether gene expression (GEP) signatures related to clear cell RCC (ccRCC) enrich for clinical benefit with nivolumab combined with ipilimumab and nivolumab and placebo in all randomized participants |
- Comparar la SG de nivolumab en combinación con ipilimumab y nivolumab y placebo en todos los participantes aleatorizados - Evaluar medidas adicionales de la eficacia en todos los participantes aleatorizados - Estimar la incidencia de acontecimientos adversos (AA) de nivolumab en combinación con ipilimumab y de nivolumab y placebo en todos los participantes aleatorizados - Investigar si las firmas de expresión génica (GEP) relacionadas con el CCR de células claras (CCRcc) enriquecen en cuanto a beneficio clínico con nivolumab en combinación con ipilimumab y nivolumab y placebo en todos los participantes aleatorizados |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histological confirmation of renal carcinoma with clear cell component including participants who may have sarcomatoid features. - Advanced (not amenable to curative surgery or radiation therapy) renal cell carcinoma (RCC) or metastatic RCC (mRCC). - Measurable disease by CT or MRI per RECIST 1.1 criteria. - No prior systemic therapy for RCC - Must be intermediate or poor risk as per International Metastatic RCC Database Consortium (IMDC). |
- Confirmación histológica de carcinoma renal con componente de células claras, incluidos pacientes que puedan tener rasgos sarcomatoides. - Carcinoma de células renales (CCR) avanzado (no susceptible de cirugía o radioterapia curativas) o carcinoma de células renales metastásico (CCRm). - Enfermedad medible mediante tomografía computarizada (TC) o resonancia magnética (RM) según los criterios RECIST 1.1. - No haber recibido ningún tratamiento sistémico previo para CCR. - Los participantes deben tener un riesgo intermedio o alto según la IMDC (International Metastatic RCC Database Consortium). |
|
E.4 | Principal exclusion criteria |
- Any active central nervous system (CNS) metastases. - Active, known, or suspected autoimmune disease - Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA-4 antibody, or any other agents specifically targeting T-cell co stimulation or checkpoint pathways |
- Cualquier metástasis del sistema nervioso central (SNC) activa. - Enfermedad autoinmune activa, conocida o sospechosa. - Tratamiento previo con un anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anticuerpo anti CTLA-4, o cualquier otro agente que se dirige específicamente a la co-estimulación de las células T o a las vías de control. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression free survival (PFS) by BICR 2. Overall Response Rate (ORR) by BICR |
1. Supervivencia libre de progresión (SLP) de acuerdo con la revisión central independiente enmascarada (RCIE) 2. Tasa de respuesta objetiva (TRO) de acuerdo con la revisión central independiente enmascarada (RCIE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 34 months 2. Up to 23 months |
1. Hasta 34 meses 2. Hasta 23 meses |
|
E.5.2 | Secondary end point(s) |
3. Overall survival (OS) 4. Overall response rate (ORR) by Investigator 5. Disease control rate (DCR) 6. Duration of response (DoR) 7. Time to objective response (TTR) 8. Progression free survival (PFS) and PFS2 per Investigator 9. Incidence of adverse events (AEs) 10. PFS, ORR and OS based on GEP signatures |
3. Supervivencia global (SG) 4. Tasa de respuesta objetiva (TRO) según el investigador 5. Tasa de control de la enfermedad (TCE) 6. Duración de la respuesta (DdR) 7. Tiempo hasta la respuesta objetiva (THR) 8. Supervivencia libre de progresión (SLP) y SLP2 según el investigador 9. Incidencia de acontecimientos adversos (AAs) 10. SLP, TRO y SG basadas en las firmas de GEP |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
3. Up to 5 years 4. Up to 4 years 5. Up to 4 years 6. Up to 4 years 7. Up to 4 years 8. Up to 4 years 9. Up to 4 years 10. Up to 4 years |
3. Hasta 5 años 4. Hasta 4 años 5. Hasta 4 años 6. Hasta 4 años 7. Hasta 4 años 8. Hasta 4 años 9. Hasta 4 años 10. Hasta 4 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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Inmunogenicidad |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 |
Austria |
Chile |
Czech Republic |
France |
Greece |
Ireland |
Italy |
Mexico |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
|
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
|
LPLV |
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 | 2 |
E.8.9.1 | In the Member State concerned days | 22 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 21 |