E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary central nervous system (CNS) malignancies. |
Neoplasias malignas primarias del SNC de alto grado. |
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E.1.1.1 | Medical condition in easily understood language |
Primary central nervous system (CNS) malignancies. |
Neoplasias malignas primarias del SNC de alto grado. |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006153 |
E.1.2 | Term | Brain tumor |
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 estimate anti-tumor activity of study treatments, based on duration of disease control and survival, of children and adolescents with CNS malignancies. |
Estimar la actividad antitumoral de los tratamientos del ensayo, en base a la duración del control de la enfermedad y supervivencia, de niños y adolescentes con tumores primarios del SNC. |
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E.2.2 | Secondary objectives of the trial |
To describe the safety and tolerability of study treatments in children and adolescents with CNS malignancies. |
Estimar la seguridad y la tolerabilidad del tratamiento del ensayo en niños y adolescentes con tumores primarios del SNC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1-Children and adolescents diagnosed with either: _Diffuse Intrinsic Pontine Glioma (DIPG), _High Grade Glioma (HGG), _Medulloblastoma, _Ependymoma, or _Other high-grade tumors of the central nervous system. 2-Lansky play score (LPS) for =< 16 years of age or Karnofsky performance scale (KPS) for > 16 years of age assessed within two weeks of enrollment must be >= 60. 3-A tumor sample must be available for submission to central laboratory [not required for DIPG]. |
1) Niños y adolescentes diagnosticados con: - Glioma Pontino Intrinseco Difuso (GPID). - Glioma de Alto Grado (GHG). - Meduloblastoma. - Ependimoma o, - Otros tumors del SNC de alto grado. 2) Escala de Lansky (LPS) para ≤ 16 años de edad o índice de Karnofsky (KPS) para > 16 años de edad evaluado dentro de las dos semanas de reclutamiento debe ser ≥ 60. 3) Debe estar disponible una muestra del tumor para su envío al laboratorio central [no se requiere para GPID]. |
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E.4 | Principal exclusion criteria |
1-Participants with active, known or suspected autoimmune disease. 2-Participants unable to taper steroids due to ongoing mass effect. 3-Participants with low-grade gliomas or tumors of unknown malignant potential. 4-Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors). |
1) Pacientes con enfermedad autoinmune activa conocida o sospechada. 2) Pacientes en los que no sea posible disminuir la dosis de esteroides debido al efecto de masa del tumor. 3) Pacientes con glioma de bajo grado o tumores de potencial maligno desconocido. 4) Pacientes que hayan recibido un tratamiento previo con cualquier medicamento dirigido a la coestimulación de células T (como los inhibidores del punto de control). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1- Safety Lead In: Safety and tolerability: DLTs, SAEs, AEs leading to discontinuation; 2- Diffuse Intrinsic Pontine Glioma (DIPG): Overall Survival (OS); 3- All other tumor types: Progression Free Survival (PFS). |
1) Seguridad y tolerabilidad: DLTs, efectos adversos graves, efectos adversos que produzcan la interrupción del tratamiento; 2) Glioma Pontino Intrinseco Difuso (GPID): Supervivencia Global (SG). 3) Otro tipo de tumores: Supervivencia Libre de Progresión (SLP). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 6 weeks for (1); Approximately 3 years (from first patient treated) for (2); Approximately 2 years for (3) |
Aproximadamente seis semanas para el objetivo 1; aproximadamente tres años (desde el primer paciente tratado) para el objetivo 2; aproximadamente dos años para el objetivo 3. |
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E.5.2 | Secondary end point(s) |
1- Safety: AEs, SAEs, drug-related AEs, AEs leading to discontinuation, and death. Incidence of laboratory abnormalities; 2- Diffuse Intrinsic Pontine Glioma (DIPG): Progression Free Survival (PFS); 3- Diffuse Intrinsic Pontine Glioma (DIPG): Overall Survival at 12 month point (OS(12)); 4- High Grade Glioma (HGG), Medulloblastoma, Ependymoma, and other high-grade CNS tumors: Progression Free Survival at 6 months (PFS(6)); 5- High Grade Glioma (HGG), Medulloblastoma, Ependymoma, and other high-grade CNS tumors: Overall Survival (OS); 6- High Grade Glioma (HGG), Medulloblastoma, Ependymoma: Overall Survival at 12 month point (OS(12)). |
1) Seguridad: efectos adversos, efectos adversos graves, efectos adversos relacionados con el medicamento que producen la interrupción del tratamiento y la muerte. Incidencia de anormalidades de laboratorio. 2) GPID: SLP 3) GIPD: SG a los 12 meses. 4) Glioma de alto grado, Meduloblastoma, Ependimoma y otros tumores del SNC de alto grado: SLP a los 6 meses. 5) Glioma de alto grado, Meduloblastoma, Ependimoma y otros tumores del SNC de alto grado: SG. 6) Glioma de alto grado, Meduloblastoma, Ependimoma y otros tumores del SNC de alto grado: SG a los 12 meses. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 3 years for (1) and (5); Approximately 18 months to 2 years from first patient treated for (2) and (4); Approximately 24 months to 3 years for (3) and (6). |
Aproximadamente 3 años para los objetivos 1 y 5; aproximadamente de 18 meses a 2 años desde el primer paciente tratado para los objetivos 2 y 4; aproximadamente de 24 meses a 3 años para los objetivos 3 y 6. |
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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 | 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) | 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 |
PD activity and PK parameters in paediatric participants |
Actividad farmacodinámica y parámetros farmacocinéticos en pacientes pediátricos. |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Denmark |
France |
Germany |
Hong Kong |
Israel |
Netherlands |
Norway |
Poland |
Russian Federation |
Spain |
Sweden |
United Kingdom |
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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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LVLS |
Última visita del último paciente (LPLV). |
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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 | 5 |
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 | 5 |
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 |