E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular Carcinoma |
Carcinoma hepatocelular |
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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. |
El propósito principal de este estudio es comparar la Supervivencia General (SG) de nivolumab más ipilimumab frente al tratamiento estándar (standard of care, SOC) (sorafenib o lenvatinib) en todos los participantes aleatorizados con CHC en estadio avanzado que no han recibido tratamiento sistémico anterior. |
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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]). |
* Comparar la TRO [evaluada por la RCIE basada en RECIST 1.1] de nivolumab más ipilimumab frente al tratamiento estándar (standard of care, SOC) (sorafenib o lenvatinib) en todos los participantes aleatorizados con CHC en estadio avanzado que no han recibido tratamiento sistémico anterior. * Comparar la DR [evaluada por la RCIE basada en RECIST 1.1] de nivolumab más ipilimumab frente al tratamiento estándar (standard of care, SOC) (sorafenib o lenvatinib) en todos los participantes aleatorizados con CHC en estadio avanzado que no han recibido tratamiento sistémico anterior. * Comparar la carga sintomática relacionada con el cáncer para los participantes aleatorizados a nivolumab más ipilimumab o al 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 |
-Los participantes deben tener un diagnóstico de CHC basado en la confirmación histológica -Los participantes deben tener CHC avanzado -Los participantes deben tener al menos una lesión medible no tratada previamente según los Criterios de evaluación de la respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors, RECIST) 1.1. -Puntuación Child-Pugh de 5 o 6. -Estado funcional según el Grupo Oncológico Cooperativo de la Costa Este (Eastern Cooperative Oncology Group, ECOG) de 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. |
-CHC fibrolamelar, CHC sarcomatoide o colangiocarcinoma mixto y CHC conocidos -Trasplante de hígado previo -Episodios de encefalopatía hepática (superior o igual a [>=] grado 2) en los 12 meses anteriores a la aleatorización -Metástasis cerebrales o leptomeníngeas activas
Pueden aplicar otros criterios de inclusion/ exclusion según protocolo. |
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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). |
SG, definida como el intervalo entre la fecha de la aleatorización y la fecha de la muerte (por cualquier 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 |
Seguimiento durante en tratamiento y después del tratamiento hasta muerte o pérdida de seguimiento. |
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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 |
-TRO, definida como el porcentaje de participantes cuya MRG es una RP o RC confirmada. -DR, definida como el tiempo desde la primera evidencia documentada de una respuesta de RC o RP hasta la primera progresión de la enfermedad documentada o la muerte por cualquier causa, lo que ocurra primero. -THDS, definida como el tiempo desde la aleatorización hasta un descenso clínicamente significativo en la puntuación de la subescala de HCS de FACT-Hep. -SSP, definido como el tiempo desde la aleatorización hasta la progresión de la enfermedad o la muerte debida a cualquier causa, lo que ocurra primero. -THP, definido como el tiempo desde la aleatorización hasta la primera progression documentada de la enfermedad. |
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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 |
Incidencia de AAs, AAGs, muertes y anomalías de laboratorio en todos los participantes tratados. |
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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 | 10 |
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 | 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 |
Chile |
China |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
New Zealand |
Poland |
Puerto Rico |
Romania |
Russian Federation |
Singapore |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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 |
La última visita o procedimiento programado para el último participante. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |