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 avanzato a cellule renali precedentemente non trattato con fattori di rischio intermedi o bassi |
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E.1.1.1 | Medical condition in easily understood language |
Renal Cell Carcinoma |
Carcinoma renale avanzato |
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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 | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
• Confrontare la PFS di nivolumab in combinazione con ipilimumab e nivolumab in combinazione con placebo in tutti i pazienti randomizzati usando i criteri RECIST 1.1. • Confrontare l’ORR di nivolumab in combinazione con ipilimumab e nivolumab in combinazione con placebo in tutti i pazienti randomizzati usando i criteri RECIST 1.1. |
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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 - To explore association of baseline PD-L1 expression on tumor with clinical benefit |
• Confrontare l’OS di nivolumab in combinazione con ipilimumab e nivolumab in combinazione con placebo in tutti i pazienti randomizzati. • Valutare le misure di efficacia aggiuntive in tutti i partecipanti randomizzati. • Stimare l’incidenza degli eventi avversi (EA) di nivolumab in combinazione con ipilimumab e nivolumab in combinazione con placebo in tutti i partecipanti trattati. • Stabilire se le firme di espressione genica (gene expression, GEP) associate al CCR a cellule chiare (clear cell RCC, ccRCC) migliorino il beneficio clinico di nivolumab in combinazione con ipilimumab e nivolumab in combinazione con placebo in tutti i pazienti randomizzati. - esplorare l’associazione dell’espressione tumorale basale di PD-L1 con il beneficio clinico |
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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 |
Pharmacogenomics Version: Revised Protcol 01 Date: 05/03/2019 Title: NA Objectives: NA
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Farmacogenomica Versione: Revised Protcol 01 Data: 05/03/2019 Titolo: Studio di fase 3b, randomizzato, in doppio cieco di nivolumab in combinazione con ipilimumab rispetto a nivolumab in monoterapia in pazienti con carcinoma avanzato a cellule renali precedentemente non trattato con fattori di rischio intermedi o bassi Obiettivi: Additional Research Sezione 9.8.1 del Protocollo
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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). |
- conferma istologica del carcinoma renale con componente di cellule chiare compresi i partecipanti che potrebbero avere caratteristiche sarcomatoidi. - carcinoma renale Avanzato (RCC) o metastatico RCC (mRCC), (non suscettibile di chirurgia curativa o radioterapia) - Malattia misurabile mediante CT o RM per i criteri RECIST 1.1. - Nessuna precedente terapia sistemica per RCC - rischio intermedio o basso secondo l’ International Metastatic RCC Database Consortium (IMDC). |
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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
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- Qualsiasi metastasi attiva del sistema nervoso centrale (SNC). - Malattia autoimmune attiva, nota o sospetta - Trattamento precedente con anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anticorpi anti-CTLA-4, o qualsiasi altro agente specifico per la co-stimolazione della cellula T. |
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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. Progression free survival (PFS) per BICR 2. Overall Response Rate (ORR) per BICR |
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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. fino a 34 mesi 2. fino a 23 mesi |
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E.5.2 | Secondary end point(s) |
3. Overall survival (OS) 4. Overall response rate (ORR) by Investigator 5. Disease control rate (DCR) by Investigator and by blinded ndependent central review (BICR) 6. Duration of response (DoR) by Investigator and by blinded independent central review (BICR) 7. ime to objective response (TTR) by Investigator and by blinded independent central review (BICR 8. Progression free survival (PFS) and PFS2 per Investigator 9. Incidence of adverse events (AEs), Serious Adverse Events, drug-related SAEs and significant changes in laboratory tests (Hematology tests, Coagulation tests), Clinical Chemistry Tests and Serology Tests) 10. PFS, ORR and OS based on GEP signatures 11.Overall Survival based on programmed cell death protein ligand-1 (PD-L1) expression 12. Overall response rate (ORR) by BICR based on PD-L1 expression 13. Progression Free Survival (PFS) by BICR based on PD-L1 expression) |
3. Overall Survival (OS) 4. Overall Response Rate (ORR) per lo sperimentatore 5. Disease control rate (DCR) per lo sperimentatore e per BICR 6. Duration of response (DoR) per lo sperimentatore e per BICR 7. Tempo per la risposta oggettiva (TTR) per lo sperimentatore e per BICR 8. Progression Free Survival (PFS) e PFS2 per lo sperimentatore 9. Incidenza degli eventi avversi (AEs), Eventi avversi seri, SAE correlati al farmaco in studio e modifiche significative nei test di laboratorio ( Test ematologici, test di coagulazione, test biochimici e test sierologici) 10. PFS, ORR e OS basati sulle firme GEP 11. Overall Survival basato sull’ espressione di PD-L1 ( programmed cell death protein ligand-1) 12. Overall response rate (ORR) secondo BICR basata sull’espressione di PD-L1 13. Progression Free Survival (PFS) secondo BICR basata sull’espressione di PD-L1 |
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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 11. Up to 4 years 12. Up to 4 years 13. Up to 4 years |
3. Fino a 5 anni 4. Fino a 4 anni 5. Fino a 4 anni 6. Fino a 4 anni 7. Fino a 4 anni 8. Fino a 4 anni 9. Fino a 4 anni 10. Fino a 4 anni 11. Fino a 4 anni 12. Fino a 4 anni 13. Fino a 4 anni |
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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 |
Immunogenicità |
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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 | 8 |
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 | Information not present in EudraCT |
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 |
Chile |
Mexico |
Russian Federation |
Austria |
France |
Ireland |
Italy |
Poland |
Portugal |
Romania |
Spain |
Czechia |
Argentina |
Greece |
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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
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LPLV |
LPLV – Ultima visita dell’ultimo paziente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 21 |