E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Second-line treatment for adult patient with unresectable advanced or metastatic hepatocellular cancer. |
tratamiento de segunda linea para paciente adulto con cancer hepatocelular no resecable avanzado o metastásico. |
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E.1.1.1 | Medical condition in easily understood language |
The disease under investigation is advanced liver cancer (hepatocellular carcinoma) that cannot be resected, or liver cancer (hepatocellular carcinoma) that has metastatized. |
La enfermedad investigándose es cancer de higado avanzado (carcinoma hepatocelular) que no es resecable, o cancer de higado (carcinoma hepatocelular) que ha metastatizado. |
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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 | 14.0 |
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 | 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 |
To evaluate efficacy of GC33 vs. placebo through investigator-assessed progression-free survival (PFS) in patients with unresectable advanced or metastatic hepatocellular carcinoma (HCC) previously treated with at least 1 systemic agent, with documented progressive disease, or documented adverse event(s) resulting in discontinuance of that (those) agents, stratified by level of GPC-3 expression (IHC score) |
?Evaluar la eficacia del GC33 frente a placebo en cuanto a la supervivencia sin progresión (SSP) evaluada por el investigador en pacientes con carcinoma hepatocelular (CHC) avanzado inoperable o metastásico tratados previamente con al menos un fármaco sistémico y con progresión de la enfermedad documentada o acontecimientos adversos documentados que causaron la retirada del tratamiento previo, estratificados en función del grado de expresión del GPC 3 (puntuación IHQ). |
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E.2.2 | Secondary objectives of the trial |
1. To compare treatment effect of GC33 vs. placebo on overall survival (OS) 2. To compare treatment effect of GC33 vs. placebo on disease control rate 3. To evaluate the tolerability and safety of GC33 when given as monotherapy in comparison to placebo using the NCI-CTCAE version 4.0 4. To further characterize the pharmacokinetic (PK) profile of GC33 5. To validate the GPC-3 immunohistochemistry(IHC) assay for analysis of GPC-3 expression |
? Comparar el efecto del tratamiento con GC33 frente a placebo sobre la supervivencia global (SG). ? Comparar el efecto del tratamiento con GC33 frente a placebo sobre la tasa de control de la enfermedad. ? Evaluar la tolerabilidad y la seguridad del GC33 administrado en monoterapia en comparación con placebo mediante los CTCAE del NCI, versión 4.0. ? Definir mejor el perfil farmacocinético del GC33. ? Validar el análisis inmunohistoquímico (IHQ) del GPC 3 para el estudio de la expresión del 3 GPC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ?18 years old 2. Life expectancy of at least 12 weeks 3. ECOG Performance Status of 0 or 1 4. Histologically confirmed unresectable advanced or metastatic hepatocellular carcinoma (without fibrolamellar subtype) 5. Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or documented adverse event(s) associated with prior systemic agent(s) that resulted in discontinuance of that(those) agent(s) 6. Not a candidate for curative treatments (e.g. resection, transplantation) 7. Child-Pugh A ( score of 5-6) 8. Adequate hematologic function: Platelet count ? 50x 109/L, Absolute Neutrophil Count ? 1,500/?L, Hemoglobin ? 8.0 g /dL 9. Adequate hepatic function: ALT (SGPT), AST (SGOT) ? 5 x ULN, Bilirubin ? 2 mg/ dL 10. Adequate renal function: Serum Creatinine ? 2 x ULN or calculated Creatinine Clearance ? 60 ml/min using Cockcroft and Gault formula 11. Ability to provide, for central review, a tumor tissue sample containing at least 5 % tumor cells to determine the level of GPC-3 expression by IHC. Determination of GPC-3 expression level is required prior to study entry. 12. Patients must have recovered from effects of any major surgery or significant traumatic injury at least 14 days before the first dose of study treatment 13. Measurable disease (by RECIST 1.1) prior to the administration of study treatment 14. Negative serum pregnancy test |
?Varón o mujer de edad ? 18 años. ?Esperanza de vida de al menos 12 semanas. ?Clase funcional del ECOG de 0 ó 1. ?Carcinoma hepatocelular confirmado histológicamente (sin subtipo fibrolamelar). ?Tratamiento previo con al menos un fármaco sistémico y progresión de la enfermedad documentada tras el tratamiento sistémico o acontecimientos adversos documentados del tratamiento sistémico previo que motivaron la retirada del mismo. ?No ser candidato a tratamientos curativos (por ejemplo, resección, trasplante). ?Clase A de Child Pugh (puntuación de 5 6). -Función hematológica adecuada: Recuento de plaquetas ? 50x 109/l, Recuento absoluto de neutrófilos ? 1,500/?l, Hemoglobina ? 8,0 g/dl -Función hepática adecuada: ALT (SGPT) y AST (SGOT) ? 5 x LSN, Bilirrubina ? 2 mg/dl ?Función renal adecuada: Creatinina sérica ? 2 x LSN o calculo de aclaramiento de Creatinina ? 60 ml/min usando formula Cockcroft and Gault ?Capacidad de aportar, para su revisión central, una muestra de tejido tumoral (al menos 5 % de tumor) para determinar el grado de expresión de GPC 3 mediante IHQ. La determinación de la expresión del GPC 3 en un requisito previo a la incorporación al estudio. ?Haberse recuperado de los efectos de una intervención de cirugía mayor o de un traumatismo importante al menos 14 días antes de la primera dosis del tratamiento del estudio. ?Enfermedad mensurable (según los RECIST, versión 1.1) antes de la administración del tratamiento del estudio. ?En las mujeres premenopáusicas, resultado negativo en la prueba de embarazo en suero |
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E.4 | Principal exclusion criteria |
1. Child-Pugh B or C 2. Known HCC with fibro-lamellar histology 3. Known brain or leptomeningeal metastases 4. Patients with a previous malignancy within the past 5 years are excluded(patients who had curatively treated basal cell carcinoma of the skin,early gastrointestinal cancer by endoscopic resection, and/or insitu carcinoma of the cervix and other malignancies which were considered cured and deemed by the PI to have no impact on the PFS and OS are allowed after discussion with the study medical monitor) 5. Active infectious diseases requiring treatment except for hepatitis B and C 6. NCI CTCAE version 4.0 grade 3 hemorrhage within 4 weeks of starting the study treatment 7. History of organ allograft including liver transplant 8. Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study 9. Patient who have had any anticancer treatment within 2 weeks prior to entering the study 10. Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies 11. Patients receiving Interferon therapy 12. Patients with baseline QTc > 470 ms, or patients with baseline resting bradycardia <45 beats per minutes. 13. Patients who received anticoagulation or thrombolytic agents for therapeutic purposes (except for low-dose administration for catheter clearance or for prophylactic purposes) |
?Clase B o C de Child Pugh. ?CHC con histología fibrolamelar. ?Metástasis cerebrales o leptomeníngeas. ?Antecedentes de tumor maligno (distinto del carcinoma basocelular de la piel, carcinoma cervicouterino in situ o cáncer del tubo digestivo en estadio inicial tratados con fines curativos, el último mediante resección endoscópica, u otros tumores malignos que se consideren curados y que según el investigador no tengan impacto en la SLP y SG tras acuerdo con el monitor médico del estudio) en los cinco últimos años. ?Enfermedad infecciosa activa que requiera tratamiento, excepto hepatitis B y C. ?Hemorragia de grado 3 según los CTCAE del NCI, versión 4.0., en las cuatro semanas anteriores a la primera dosis del tratamiento del estudio. ?Antecedentes de aloinjerto de órganos, como el trasplante hepático. ?Administración prevista o en curso de antineoplásicos distintos de los fármacos del estudio. ?Haber recibido tratamiento antineoplásico en las dos semanas previas a la inclusión en el estudio. ?No haberse recuperado por completo de la toxicidad asociada al tratamiento locorregional o sistémico previo contra el CHC. ?Tratamiento con interferón en dosis altas. ?Intervalo QTc basal mayor de 470 ms, o bradicardia en reposo con menos de 45 latidos por minutos en el momento basal. ?Tratamiento con anticoagulantes o trombolíticos con fines terapéuticos (excepto la administración en dosis bajas para desobstruir un catéter o con fines profilácticos) en las dos semanas previas al día 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival |
Supervivencia libre de progresión |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When PFS data mature (about 24 months from FPFV) |
Datos maduros de SLP (unos 24 meses desde primera visita del primer paciente) |
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E.5.2 | Secondary end point(s) |
Overall survival Time to progression Disease control rate |
Supervivencia global Tiempo de progresión Grado de control de la enfermedad |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Planned at the same time as primary endpoint |
planeado al mismo tiempo que el objetivo exploratorio primario |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Singapore |
Spain |
Taiwan |
United Kingdom |
United States |
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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
|
The study will continue until the last data point from the last patient (Overall Survival) is received, 12 months after the last patient was enrolled, or all patients completed the 28-day follow-up visit, whichever comes later. |
El estudio continuará hasta recibir el último dato dell último paciente (supervivencia global), 12 meses después de la inclusión del último paciente, o cuando todos los pacientes hayan completado los 28 días de seguimiento, lo que ocurra más tarde. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |