E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Treated Unresectable Hepatocellular Carcinoma |
carcinoma hepatocelular irresecable tratado anteriormente |
|
E.1.1.1 | Medical condition in easily understood language |
Unresectable Hepatocellular Carcinoma is a specific type of Liver cancer that is unable to be removed by surgery. |
El carcinoma hepatocelular irresecable es un tipo específico de cáncer de hígado que no se puede extirpar mediante 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 evaluate the efficacy of BGB-A317 through Independent Review Committee (IRC) assessed objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in previously treated, unresectable hepatocellular carcinoma (HCC) |
Evaluar la eficacia de BGB-A317 a través de la tasa de respuesta objetiva (TRO) evaluada por el Comité de revisión independiente (CRI) según los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST) Versión (v)1.1 en el carcinoma hepatocelular (CHC) irresecable tratado anteriormente |
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E.2.2 | Secondary objectives of the trial |
* To assess the efficacy of BGB-A317 through duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), and clinical benefit rate (CBR) assessed by IRC and overall survival (OS) * To assess efficacy of BGB-A317 through ORR, DOR, PFS, DCR, and CBR assessed by the investigators * To further assess the safety and tolerability of BGB-A317 in patients with previously treated unresectable HCC * To assess the health-related quality of life (HRQoL) of BGB-A317 in patients with previously treated unresectable HCC |
*Evaluar la eficacia de BGB-A317 mediante la duración de la respuesta (DR), la supervivencia sin progresión (SSP), la tasa de control de la enfermedad (TCE) y la tasa de beneficio clínico (TBC) evaluadas por el CRI y la supervivencia general (SG) *Evaluar la eficacia de BGB-A317 a través de la TRO, la DR, la SSP, la TCE y la TBC evaluadas por los investigadores *Evaluar la seguridad y la tolerabilidad de BGB-A317 en pacientes con CHC irresecable tratado anteriormente *Evaluar la calidad de vida relacionada con la salud (CdVRS) de BGB-A317 en pacientes con CHC irresecable tratado anteriormente |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed HCC 2. Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to locoregional therapy or relapsed after locoregional therapy, and not amenable to a curative treatment approach 3. Has received at least 1 line of systemic therapy for unresectable HCC Measurable disease 4. Child-Pugh score A 5. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1 6. Adequate organ function |
1. CHC confirmado histológicamente 2. Que se clasifique como enfermedad en estadio C del Barcelona Clinic Liver Cancer (BCLC) o estadio B del BCLC que no es susceptible de tratamiento locorregional o con recidiva después del mismo, y no es susceptible de un enfoque de tratamiento curativo. 3. Ha recibido al menos 1 línea de tratamiento sistémico para CHC irresecable 4. Se exige también que todos los pacientes pertenezcan a la Clase A de Child- Pugh 5. Que tengan una puntuación ≤ 1 del estado general según el Grupo de Oncología Cooperativo del Este 6. Función adecuada del órgano |
|
E.4 | Principal exclusion criteria |
1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology 2. Prior therapies targeting PD-1 or PD-L1 3. Has known brain or leptomeningeal metastasis 4. Tumor thrombus involving main trunk of portal vein or inferior vena cava 5. Loco-regional therapy to the liver within 4 weeks before enrollment 6. Medical history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc 7. Has received: a. Within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration: any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin) or any investigational therapies b. Within 14 days of the first study drug administration: sorafenib, regorafenib, or any Chinese herbal medicine or Chinese patent medicines used to control cancer 8. Active autoimmune diseases or history of autoimmune diseases that may relapse. 9. Patient with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before study drug administration |
1. CHC fibrolamelar conocido, CHC sarcomatoide o colangiocarcinoma mixto e histología del CHC 2. Terapias anteriores dirigidas a PD-1 o PD-L1 3. Tiene metástasis cerebrales o leptomeníngeas conocidas 4. Trombo tumoral que afecta al tronco principal de la vena porta o la vena cava inferior 5. Terapia locorregional para el hígado dentro de las 4 semanas antes de la inclusión 6. Antecedentes médicos de enfermedad pulmonar intersticial, neumonitis no infecciosa o enfermedades sistémicas no controladas, que incluyen diabetes, hipertensión, fibrosis pulmonar, enfermedades pulmonares agudas, etc. 7. Ha recibido: a. Dentro de los 28 días o 5 vidas medias (lo que sea más corto) de la primera administración del medicamento del estudio: cualquier quimioterapia, inmunoterapia (p. Ej., Interleucina, interferón, timoxina) o cualquier terapia de investigación segundo. Dentro de los 14 días posteriores a la primera administración del medicamento del estudio: sorafenib, regorafenib o cualquier medicamento herbario chino o medicamentos de patente china utilizados para controlar el cáncer 8. Enfermedades autoinmunes activas o antecedentes de enfermedades autoinmunes que pueden recaer. 9. Paciente con cualquier condición que requiera tratamiento sistémico con corticosteroides (> 10 mg diarios de prednisona o equivalente) u otra medicación inmunosupresora dentro de los 14 días previos a la administración del medicamento del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR (complete response [CR] + partial response [PR]) based on RECIST Version 1.1 in patients with previously treated unresectable HCC as evaluated by an IRC |
TRO (respuesta completa [RC] + respuesta parcial [RP]) en función de RECIST v 1.1 en pacientes con CHC irresecable tratado anteriormente según la evaluación de un CRI |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Per protocol |
por protocolo |
|
E.5.2 | Secondary end point(s) |
* DOR, PFS, DCR and CBR assessed by IRC, and OS * ORR, DOR. PFS, DCR and CBR assessed by Investigators * Safety and tolerability assessment of adverse events (AEs), serious adverse events (SAEs), physical examination, vital signs, electrocardiogram (ECG), and laboratory measurements * HRQoL measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Hepatocellular Carcinoma 18 Questions (EORTC QLQ HCC18) index score, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) index-score, and the 5-level version of the European Quality of Life 5-Dimensional Questionnaire (EQ-5D-5L) |
*DR, SSP, TCE y TBC evaluadas por el CRI, y SG *TRO, DR. SSP, TCE y TBC evaluadas por los investigadores *Evaluación de la seguridad y la tolerabilidad de los acontecimientos adversos (AA), acontecimientos adversos graves (AAG), exploración física, constantes vitales, electrocardiograma (ECG) y pruebas analíticas *CdVRS medida mediante la puntuación del índice de 18 preguntas sobre el carcinoma hepatocelular de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC QLQ HCC18), puntuación del índice de la escala básica de 30 elementos del Cuestionario de Calidad de vida de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC QLQ-C30), y la versión de 5 niveles del cuestionario europeo de calidad de vida de 5 dimensiones (EQ-5D-5L) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
per protocol |
por protocolo |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 35 |
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 |
China |
France |
Germany |
Italy |
Poland |
Spain |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
Study termination is defined as the time point when data collection for the patient will stop. The study will continue until the last patient has died, becomes lost to follow up, or withdraws from study, or until sponsor decides to terminate the study. |
La terminación del estudio se define como el momento en que se detiene la recopilación de datos del paciente. El estudio continuará hasta que el último paciente haya muerto, discontinue durante el seguimiento, o se retire del estudio, o hasta que el patrocinador decida finalizar el estudio. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 17 |