E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locoregional Hepatocellular Carcinoma (HCC) |
Carcinoma Hepatocelular Locorregional |
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E.1.1.1 | Medical condition in easily understood language |
Liver Cancer patients who only have cancer in their livers, but who cannot receive surgery |
Pacientes con cáncer de hígado que solo tienen cáncer en el hígado, pero que no pueden recibir cirugía. |
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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 | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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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 assess the efficacy of durvalumab monotherapy when given with transarterial chemoembolization (TACE) compared to TACE + placebo |
Evaluar la eficacia durvalumab en monoterapia cuando se administra con quimioembolización transarterial (TACE) en comparación con TACE + placebo |
|
E.2.2 | Secondary objectives of the trial |
- To assess the efficacy and safety of durvalumab and bevacizumab when given with TACE compared to TACE + placebo
-To assess the efficacy of all immunotherapy arms and TACE compared with placebo by PD-L1 expression and AFP expression level
-To assess disease-related symptoms and health-related quality of life (HRQoL) in patients treated with all immunotherapy arms and TACE compared with placebo
- To evaluate the PK and immunogenicities of all immunotherapy arms with TACE |
- Evaluar la eficacia y seguridad de durvalumab y bevacizumab cuando se administra con TACE en comparación con TACE + placebo.
- Evaluar la eficacia de todos los brazos de inmunoterapia y TACE en comparación con el placebo por la expresión de PD-L1 y el nivel de expresión de AFP.
- Evaluar los síntomas relacionados con la enfermedad y la calidad de vida relacionada con la salud (CVRS) en pacientes tratados con todos los brazos de inmunoterapia y TACE en comparación con placebo.
- Evaluar la FC y la inmunogenicidad de todos los brazos de inmunoterapia con TACE. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- No evidence of extrahepatic disease on baseline imaging - Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE - Child-Pugh score class A to B7 and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment - Measurable disease by mRECIST criteria - Adequate organ and marrow function |
- No hay evidencia de enfermedad extrahepática en las imágenes de referencia. - Enfermedad no susceptible de cirugía curativa o trasplante o ablación curativa, pero enfermedad susceptible de TACE - Puntuación de Child-Pugh clase A a B7 y estado funcional de Eastern Cooperative Oncology Group (ECOG) de 0 o 1 en el momento de la inclusión. - Enfermedad medible por criterios mRECIST. - Función adecuada de órgano y médula. |
|
E.4 | Principal exclusion criteria |
- Any history of nephrotic or nephritic syndrome - Clinically significant cardiovascular disease or history of arterioembolic event including a stroke or myocardial infarction - Any prior or current evidence of coagulopathy or bleeding diathesis or patients who had any kind of surgery in the past 28 days - History of abdominal fistula or GI perforation, non healed gastric ulcer, or active GI bleeding within 6 months prior to enrollment - Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded |
- Cualquier antecedente de síndrome nefrótico o nefrítico. - Enfermedad cardiovascular clínicamente significativa o antecedentes de evento arterioembólico, incluido un accidente cerebrovascular o un infarto de miocardio - Cualquier evidencia previa o actual de coagulopatía o diátesis hemorrágica o pacientes que hayan tenido algún tipo de cirugía en los últimos 28 días - Antecedentes de fístula abdominal o perforación gastrointestinal, úlcera gástrica no curada o sangrado gastrointestinal activo dentro de los 6 meses anteriores al reclutamiento - Se excluyen los pacientes con trombosis de la vena porta Vp3 y Vp4 en la imagen de referencia. |
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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) evaluada mediante los criterios RECIST 1.1 empleando la RCIE |
|
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 recopilarán regularmente en puntos de tiempo predefinidos hasta la progresión de la enfermedad |
|
E.5.2 | Secondary end point(s) |
Overall Survival (OS)
Objective Response Rate (ORR)
Disease Control Rate (DCR)
Duration of Response (DoR)
Time to progression (TTP)
Time from Randomization to Second Progression PFS (PFS2)
Health-related quality of life (HRQoL) patient reported outcomes |
Supervivencia global (SG)
Tasa de Respuesta Objetiva (TRO)
Tasa de Control de la Enfermedad (TCE)
Duración de la Respuesta (DR)
Tiempo hasta la Progresión (THP)
Tiempo desde la Aleatorización hasta la Segunda Progresión (SSP2)
Resultados de calidad de vida relacionada con la salud (CVRS) informados por los pacientes |
|
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 |
Se realizarán evaluaciones regularmente hasta la progresión de la enfermedad o hasta el final del ensayo |
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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 | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Australia |
Brazil |
Canada |
China |
France |
India |
Italy |
Japan |
Korea, Republic of |
Mexico |
Spain |
Taiwan |
Thailand |
United States |
Vietnam |
|
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
|
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |