E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric patients with recurrent//refractory high grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), low grade astrocytoma, neuroblastoma, ependymoma, medulloblastoma/primitive neuroectodermal tumours (PNET), rhabdomyosarcoma (RMS) and/or other solid tumours with known ErbB pathway deregulation regardless of tumour histology |
Pacientes pediátricos con glioma de gran malignidad (HGG), glioma pontino intrínseco difuso (DIPG), astrocitoma de escasa malignidad, neuroblastoma, ependimoma, meduloblastoma o tumor neuroectodérmico primitivo (PNET), rabdomiosarcoma (RMS) y/o otros tumores sólidos con una desregulación conocida de la vía de ErbB, recidivantes o refractarios. |
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E.1.1.1 | Medical condition in easily understood language |
pediatric oncology |
oncología pediátrica |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029091 |
E.1.2 | Term | Neoplasm of unspecified nature of endocrine glands and other parts of nervous system |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029006 |
E.1.2 | Term | Neoplasm of uncertain behavior of brain and spinal cord |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029050 |
E.1.2 | Term | Neoplasm of uncertain behaviour of connective and other soft tissue |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028992 |
E.1.2 | Term | Neoplasm CNS |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-Establish MTD of afatinib in pediatric patients -describe pharmacokinetics of afatinib -investigate objective response (OR) to treatment |
-Determinar la dosis máxima tolerada (MTD) de afatinib en pacientes pediátricos -Describir la farmacocinética (FC) de afatinib -Investigar la respuesta objetiva (OR) al tratamiento. |
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E.2.2 | Secondary objectives of the trial |
-Safety -pharmacokinetics -efficacy by objective reponse |
-Seguridad -Farmacocinética -Eficacia según la OR |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Paediatric patients - aged ?2 years - <18 years at the time of informed consent - who present with recurrent/refractory disease after they received at least one prior standard treatment regimen and for whom no effective conventional therapy exists - Dose finding part: patients with a diagnosis of HGG, DIPG, low grade astrocytoma, neuroblastoma, ependymoma, medulloblastoma/PNET, RMS, and/or solid tumours with known ErbB pathway deregulation regardless of tumour histology. - MTD expansion cohort: patients with solid tumours (regardless of histology) selected by any biomarker(s) for ErbB pathway deregulation, which was previously identified in a biomarker prevalence study done outside of this clinical trial protocol -Performance status >= 50% (Lansky for =<12ys; Karnofsky for >12ys) |
- Pacientes pediátricos - de ?2 años a <18 años de edad en el momento de otorgar el consentimiento informado - que presentan enfermedad recidivante o refractaria después de recibir al menos un tratamiento de referencia previo, y para los cuales no existe ningún tratamiento tradicional eficaz - Parte de búsqueda de dosis: pacientes con diagnóstico de HGG, DIPG, astrocitoma de escasa malignidad, neuroblastoma, ependimoma, meduloblastoma o PNET, RMS y/o tumores sólidos con una desregulación conocida de la vía de ErbB sin tener en cuenta la histología del tumor. - Cohorte de ampliación de MTD: pacientes con tumores sólidos (sin tener en cuenta la histología) seleccionados por cualquier biomarcador para la desregulación de la vía de ErbB, que se ha identificado previamente en un estudio de prevalencia de biomarcadores realizado fuera de este protocolo de ensayo clínico. -Estado funcional >= 50% (Lansky for =<12ys; Karnofsky for >12ys) |
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E.4 | Principal exclusion criteria |
-relevant toxicity from previous treatment -known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis |
-toxicidad relevante en tratamiento previo -insuficiencia cardíaca, hepática renal o de médula ósea preexistente, conocida y relevante, ILD, keratitis |
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E.5 End points |
E.5.1 | Primary end point(s) |
In dose finding part 1) DLT measured during the first course of treatment 2) Pharmacokinetics (AUC, Cmax, tmax and accumulation (or effective) half-life)
In MTD expansion cohort 3)Objective Response by investigator assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression of disease. |
En la parte de búsqueda de dosis: 1) Toxicidad limitante de la dosis (DLT) determinada durante la primera parte del tratamiento 2) Farmacocinética(AUC, Cmax, tmax y semivida de acumulación (o efectiva))
En la cohorte de ampliación MTD: 3) Respuesta objetiva (OR) evaluada por el investigador mediante los criterios del centro, según el tipo de tumor estudiado, realizado cada 8 semanas hasta que se produzca la progresión de la enfermedad |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: up to 1 year
2: up to 1 year
3: up to 2 years |
1: hasta 1 año
2: hasta 1 año
3: hasta 2 años |
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E.5.2 | Secondary end point(s) |
In dose finding part 1) Objective Response by investigator assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression of disease.
In MTD expansion cohort 2) Progression free survival (PFS) 3) Pharmacokinetics (AUC, Cmax, tmax and accumulation (or effective) half-life) |
En la parte de búsqueda de dosis: 1)Respuesta objetiva (OR) evaluada por el investigador mediante los criterios del centro, según el tipo de tumor estudiado, realizado cada 8 semanas hasta que se produzca la progresión de la enfermedad
En la cohorte de ampliación MTD: 2) Supervivencia sin progresión (PFS) 3) Farmacocinética(AUC, Cmax, tmax y semivida de acumulación (o efectiva)) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: up to 2 years
2: up to 2 years
3: up to 2 years |
1: hasta 2 años
2: hasta 2 años
3: hasta 2 años |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
efficacy assessment in biomarker preselected patients |
evaluación de la eficacia en pacientes con biomarcador preseleccionado |
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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 |
phase I trial in paediatric population |
estudio de fase I en población pediátrica |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
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 | 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 |
Austria |
Canada |
Denmark |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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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
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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 | 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 |