E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular Carcinoma |
Carcinoma epatocellulare |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049010 |
E.1.2 | Term | Carcinoma hepatocellular |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
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 |
The main purpose of this study is to compare the overall survival (OS) of nivolumab plus ipilimumab versus standard of care (SOC) (sorafenib or lenvatinib) in all randomized participants with advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy. |
L'obiettivo principale di questo studio è confrontare l’OS di nivolumab più ipilimumab rispetto alla terapia SOC (sorafenib o lenvatinib) in tutti i partecipanti randomizzati affetti da HCC avanzato che non hanno ricevuto precedente terapia sistemica. |
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E.2.2 | Secondary objectives of the trial |
To compare the ORR [as assessed by BICR based on RECIST 1.1] of nivolumab plus ipilimumab to SOC (sorafenib or lenvatinib) in all randomized participants with advanced HCC who have not received prior systemic therapy. To evaluate DOR [as assessed by BICR based on RECIST 1.1] of nivolumab plus ipilimumab and SOC (sorafenib or lenvatinib) in all randomized participants with advanced HCC who have not received prior systemic therapy. To compare the cancer-related symptom burden for participants randomized to nivolumab plus ipilimumab or SOC [sorafenib or lenvatinib]). |
Confrontare l’ORR [valutato mediante revisione centrale indipendente in cieco (BICR) in base ai criteri RECIST 1.1] di nivolumab più ipilimumab con la terapia SOC (sorafenib o lenvatinib) in tutti i partecipanti randomizzati affetti da HCC avanzato che non hanno ricevuto precedente terapia sistemica. Confrontare la DOR [valutata mediante BICR in base ai criteri RECIST 1.1] di nivolumab più ipilimumab rispetto alla terapia SOC (sorafenib o lenvatinib) in tutti i partecipanti randomizzati affetti da HCC avanzato che non hanno ricevuto precedente terapia sistemica. Confrontare il carico sintomatologico correlato al tumore per i partecipanti randomizzati a nivolumab più ipilimumab o alla terapia SOC (sorafenib o lenvatinib). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participants must have a diagnosis of HCC based on histological confirmation - Participants must have an advanced HCC - Participants must have at least one Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable previously untreated lesion - Child-Pugh score 5 or 6 - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 |
- I partecipanti devono presentare una diagnosi di HCC confermata istologicamente - I partecipanti devono essere affetti da HCC avanzato - I partecipanti devono presentare almeno una lesione precedentemente non trattata misurabile secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST) 1.1 - Punteggio Child-Pugh 5-6 - Eastern Cooperative Oncology Group (ECOG) Performance status (PS) di 0 o 1 |
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E.4 | Principal exclusion criteria |
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC - Prior liver transplant - Episodes of hepatic encephalopathy (greater than or equal to [>=] Grade 2) within 12 months prior to randomization - Active brain metastases or leptomeningeal metastases
Other protocol inclusion/exclusion criteria may apply. |
- HCC fibrolamellare noto, HCC sarcomatoide, o colangiocarcinoma e HCC misti - Precedente trapianto di fegato - Episodi di encefalopatia epatica (maggiori o uguali a [>=] Grado 2) nei 12 mesi precedenti la randomizzazione - Metastasi cerebrali o leptomeningee attive
Possono essere applicati altri criteri di inclusione/esclusione del protocollo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- OS, defined as the time between the date of randomization and the date of death (by any cause). |
- OS, definita come l’intervallo tra la data di randomizzazione e la data di decesso (per qualsiasi causa). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment and post treatment follow up until death or lost of follow up |
Follow up durante e dopo il trattamento fino al decesso o alla perdita al follow up |
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E.5.2 | Secondary end point(s) |
- ORR, defined as the percentage of participants whose BOR is either a confirmed CR or PR.; - DOR, defined as the time from the first documented evidence of a response of CR or PR until the first documented disease progression or death due to any cause, whichever occurs first; - TTSD, defined as the time from randomization until a clinically meaningful decline in the HCS subscale score of the FACT-Hep.; - PFS, defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.; - TTP, defined as the time from randomization to the first documented disease progression |
- ORR, definito come la percentuale di partecipanti la cui BOR è una CR o PR confermata.; - DOR, definita come l’intervallo tra la prima evidenza documentata di una risposta CR o PR fino alla prima progressione della malattia documentata o al decesso per qualsiasi causa, a seconda di quale evento si verifichi prima; - TTSD, definito come l’intervallo tra la randomizzazione e una riduzione clinicamente significativa nel punteggio della sottoscala relativa all’HCS del questionario di valutazione funzionale della terapia del tumore del distretto epatobiliare (FACT-Hep).; PFS, definita come l’intervallo di tempo compreso tra la randomizzazione e la prima progressione della malattia documentata o il decesso per qualsiasi causa, a seconda dell’evento che si verifica per primo.; TTP, definito come l’intervallo di tempo compreso tra la randomizzazione e la prima progressione della malattia documentata |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Incidence of AEs, SAEs, deaths and laboratory abnormalities in all treated participants; Incidence of AEs, SAEs, deaths and laboratory abnormalities in all treated participants; Incidence of AEs, SAEs, deaths and laboratory abnormalities in all treated participants; Incidence of AEs, SAEs, deaths and laboratory abnormalities in all treated participants; Incidence of AEs, SAEs, deaths and laboratory abnormalities in all treated participants |
Incidenza di EA, SAE, decessi e anomalie di laboratorio in tutti i partecipanti trattati; Incidenza di EA, SAE, decessi e anomalie di laboratorio in tutti i partecipanti trattati; Incidenza di EA, SAE, decessi e anomalie di laboratorio in tutti i partecipanti trattati; Incidenza di EA, SAE, decessi e anomalie di laboratorio in tutti i partecipanti trattati; Incidenza di EA, SAE, decessi e anomalie di laboratorio in tutti i partecipanti trattati |
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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 | No |
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 | No |
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 | 85 |
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 |
Australia |
Brazil |
Canada |
Chile |
China |
Hong Kong |
Japan |
Korea, Republic of |
New Zealand |
Puerto Rico |
Russian Federation |
Singapore |
Taiwan |
United States |
Austria |
Belgium |
France |
Germany |
Italy |
Poland |
Romania |
Spain |
Switzerland |
United Kingdom |
Czechia |
Argentina |
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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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The last visit or scheduled procedure for the last participant |
L'ultima visita o procedura pianificata per l'ultimo partecipante |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |