E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locoregional Hepatocellular Carcinoma (HCC) |
Carcinoma Hepatocelular Locorregional (CHC). |
|
E.1.1.1 | Medical condition in easily understood language |
Liver cancer patients who only have cancer in their livers but cannot receive therapies intended to cure disease e.g. resection, ablation, liver transplantation |
Pacientes con cáncer de hígado que sólo tienen cáncer en su hígado, pero no pueden recibir terapias con intención de curar la enfermedad, por ejemplo, resección, ablación o trasplante hepático |
|
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
|
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 demonstrate superiority of durvalumab + tremelimumab + lenvatinib + TACE relative to TACE alone by assessment of PFS in participants with locoregional HCC |
Demostrar la superioridad de durvalumab + tremelimumab + lenvatinib + TACE frente a la TACE sola mediante la evaluación de la SSP en participantes con CHC locorregional |
|
E.2.2 | Secondary objectives of the trial |
To demonstrate superiority of durvalumab + tremelimumab + TACE relative to TACE alone by assessment of PFS in participants with locoregional HCC
To demonstrate superiority of durvalumab + tremelimumab + lenvatinib + TACE relative to TACE alone by assessment of OS in participants with locoregional HCC
To demonstrate superiority of durvalumab + tremelimumab + TACE relative to TACE alone by assessment of OS in participants with locoregional HCC |
Demostrar la superioridad de durvalumab + tremelimumab + TACE frente a la TACE sola mediante la evaluación de la SSP en participantes con CHC locorregional
Demostrar la superioridad de durvalumab + tremelimumab + lenvatinib + TACE frente a la TACE sola mediante la evaluación de la SG en participantes con CHC locorregional
Demostrar la superioridad de durvalumab + tremelimumab + TACE frente a la TACE sola mediante la evaluación de la SG en participantes con CHC locorregional |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- No evidence of extrahepatic disease - Disease not amenable to curative surgery or transplantation or curative ablation - Disease must be amenable to TACE - Child-Pugh score class A and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria - Adequate organ and marrow function |
- Sin evidencia de enfermedad extrahepática - Enfermedad no candidata a cirugía curativa o transplante o ablación curativa. - La enfermedad debe ser candidata a TACE. - Escala Child-Pugh clase A y Eastern Cooperative Oncology Group (ECOG) estado funcional de 0 ó 1. - Enfermedad medible mediantes Criterio de Respuesta Modificada en Tumores Solidos (mRECIST). - Adecuada función orgánica y de la médula ósea. |
|
E.4 | Principal exclusion criteria |
- History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardia arrhythmia - History of encephalopathy within past 12 months - Uncontrolled arterial hypertension - Co-infection with HBV and HDV - Major portal vein thrombosis visible on baseline imaging |
- Historia de fallo cardiaco congestivo sintomático, angina pectoris inestable, arritmia cardiaca no controlada. - Historia de encefalopatía en los últimos 12 meses. - Hipertensión arterial no controlada. - Co-infección con virus de la hepatitis B y virus de la hepatitis D. - Trombosis venosa portal mayor visible en imagen basal. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR |
Supervivencia Sin progresión (SSP) por RECIST 1.1. evaluado por Evaluación Central Independiente Enmascarada (ECIE) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments for PFS will be collected regularly at predefined time points until disease progression |
Las evaluaciones de SSP se recogerán regularmente en los tiempos predefinidos hasta progresión de enfermedad. |
|
E.5.2 | Secondary end point(s) |
Overall Survival (OS) |
Supervivencia Global (SG) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments will be made regularly until disease progression or until the end of the study |
Las evaluaciones se harán regularmente hasta progresión de enfermedad o hasta final del ensayo. |
|
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Brazil |
Canada |
China |
Egypt |
India |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Philippines |
Taiwan |
Thailand |
United States |
Viet Nam |
France |
Spain |
Germany |
Italy |
Portugal |
Russian Federation |
|
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
|
Last expected visit/contact of the last patient undergoing the study |
La última visita/contacto del último paciente del estudio. |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 5 |