E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular Carcinoma |
carcinoma hepatocelular |
|
E.1.1.1 | Medical condition in easily understood language |
Liver Cancer |
Cancer de Higado |
|
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 | 16.1 |
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 |
Determine the recommended phase II dose (RP2D) of MSC2156119J.
Evaluate efficacy of MSC2156119J in subjects with MET+ advanced HCC pretreated with sorafenib and Child Pugh class A liver function. |
Determinar la DRF2 de MSC2156119J.
Evaluar la eficacia de MSC2156119J en sujetos con CHC avanzado MET+ tratados previamente con sorafenib y con función hepática de clase A de Child Pugh. |
|
E.2.2 | Secondary objectives of the trial |
Characterize the single and multiple dose pharmacokinetics (PK) of MSC2156119J. Assess antitumor activity and biochemical response of MSC2156119J. Evaluate safety and tolerability of MSC2156119J.
Evaluate the safety and tolerability of MSC2156119J. Evaluate antitumor activity and biochemical response of MSC2156119J |
Determinar la FC de dosis únicas y múltiples de MSC2156119J. Evaluar la actividad antitumoral y la respuesta bioquímica de MSC2156119J. Evaluar la seguridad y la tolerabilidad de MSC2156119J.
Evaluar la seguridad y la tolerabilidad de MSC2156119J. Evaluar la actividad antitumoral y la respuesta bioquímica de MSC2156119J. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed HCC; 2. Child Pugh Class A liver function score; 3. For phase II only: MET+ status 4. Male or female, 18 years of age or older; 5. Measurable disease in accordance with RECIST Version 1.1; 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (inclusive); 7. Previously treated with sorafenib for ? 4 weeks and discontinued sorafenib treatment at least 14 days prior to Day 1 due to either intolerance or radiographic progression; 8. Signed and dated informed consent indicating that the subject (or legally acceptable representative if applicable by local laws) has been informed of all the pertinent aspects of the trial prior to enrollment; 9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures; and 10. Life expectancy of at least 3 months as judged by the investigator. |
1. CHC confirmado mediante histología o citología. 2. Función hepática de clase A de Child Pugh. 3. Para la Fase II solo: Estado MET+ 4. Hombre o mujer con una edad mínima de 18 años. 5. Enfermedad mensurable de acuerdo con los criterios RECIST, versión 1.1. 6. Grado de actividad del Grupo Oncológico Cooperativo del Este (ECOG) de 0-1 (inclusive). 7. Tratamiento previo con sorafenib durante ? 4 semanas y suspensión del mismo al menos 14 días antes del día 1 por intolerancia o progresión radiológica. 8. Consentimiento informado firmado y fechado en el que se indique que se ha informado al sujeto (o a su representante legal si procede según la legislación local) de todos los aspectos pertinentes del ensayo antes del registro. 9. Disposición a cumplir las visitas programadas, el plan de tratamiento, las pruebas analíticas y otros procedimientos del ensayo;y 10. Esperanza de vida mínima de 3 meses a juicio del investigador. |
|
E.4 | Principal exclusion criteria |
1. Prior systemic anticancer treatment for advanced HCC (except for sorafenib as described in the inclusion criteria); 2. Prior treatment with any agent targeting the HGF/c-Met pathway; 3. Local-regional therapy within 4 weeks before Day 1 4. Impaired cardiac function 5. Additional exclusion criteria could apply. |
1. Tratamiento antineoplásico sistémico previo para el CHC avanzado (excepto sorafenib, según se describe en los criterios de inclusión). 2. Tratamiento previo con cualquier fármaco que actúe sobre la vía del HGF/c-Met. 3. Tratamiento locorregional en las 4 semanas previas al día 1. 4. Disfunción cardíaca 5. Criterios de exclusion adicionales podrían aplicar |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib: Number of DLTs occuring in Cycle 1
Phase II: Progression-free survival (PFS) status at 12 weeks |
Fase Ib: incidencia de las TLD que se produzcan durante el ciclo 1.
Fase II: estado de supervivencia sin progresión (SSP) a las 12 semanas |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Time to Progression according to RECIST v. 1.1 -Progression free survival according to RECIST v. 1.1 and mRECIST for HCC -Time-to-symptomatic progression according to RECIST v. 1.1 -Overall survival -Best overall response rate -Disease control rate -Biological response rate |
-Tiempo Hasta Progresion (THP) conforme a los criterios RECIST, versión 1.1 y mRECIST para CHC -Tiempo hasta la progresión sintomática conforme a los criterios RECIST. - Supervivencia Global - Mejor tasa de respuesta global - Tasa de control de la enfermedad - Tasa de respuesta biológica |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
? To determine the recommended phase II dose (RP2D) of MSC2156119J |
|
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
| 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 | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
The end of the trial will be defined as 12 months after the last subject?s first dose of MSC2156119J. Subjects who are on active treatment with MSC2156119J at the time of end of the trial will be offered further treatment with MSC2156119J and assessments will be made as appropriate to determine whether a potential benefit from further treatment is seen. |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |