E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
standard risk hepatoblastoma |
hepatoblastoma estándar |
|
E.1.1.1 | Medical condition in easily understood language |
liver tumour typical of children |
tumor hepático típico de la edad infantil |
|
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 | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10019825 |
E.1.2 | Term | Hepatoblastomas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019824 |
E.1.2 | Term | Hepatoblastoma resectable |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 assess the efficacy of STS to reduce the hearing impairment caused by Cisplatin chemotherapy |
Evaluar la eficacia de STS para reducir la deficiencia auditiva provocada por la quimioterapia con cisplatino |
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E.2.2 | Secondary objectives of the trial |
To carefully monitor any potential impact of STS on response to Cisplatin and survival. To assess the short- and long-term tolerability of the combination of STS and Cisplatin. To prospectively evaluate and validate biological, radiological and pathological features of standard risk hepatoblastoma for future risk adapted management. To investigate the effect of STS on the formation of Cisplatin-DNA adducts. To prospectively collect patient DNA specifically for the analysis of possible genetic factors that may contribute to the development of treatment related ototoxicity and nephrotoxicity |
Controlar exhaustivamente cualquier impacto potencial de STS en la respuesta a cisplatino y la supervivencia. Evaluar la tolerabilidad a corto y largo plazo de la combinación de STS y cisplatino. Evaluar y validar de manera prospectiva características biológicas, radiológicas y patológicas del hepatoblastoma de riesgo estándar para el tratamiento futuro adaptado al riesgo. Investigar el efecto de STS en la formación de complejos cisplatino-ADN. Recoger de manera prospectiva ADN de los pacientes específicamente para el análisis de posibles factores genéticos que podrían contribuir al desarrollo de ototoxicidad y nefrotoxicidad relacionadas con el tratamiento |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically confirmed newly diagnosed hepatoblastoma Standard risk hepatoblastoma (defined in section 10.1) Age ≤ 18 years and > 1 month Written informed consent and national/local ethics committee and regulatory approval Centre/country willing and able to organise audiometry at the minimum required quality standard and to provide the contact details of the Consultant Audiologist or Ear Nose and Throat Surgeon who will take the responsibility for seeing that this is done (see Section 15.9) Ability to comply with requirements for submission of material for central review For females of child-bearing potential, a negative pregnancy test prior to study treatment is required. Any patient who is of reproductive age should agree to use adequate contraception for the duration of the trial. |
Hepatoblastoma diagnosticado recientemente confirmado histológicamente Hepatoblastoma de riesgo estándar: PRETEXT I, II o III Alfafetoproteína sérica (AFP) > 100 µg//l Ningún criterio de PRETEXT adicional Edad 18 años y > 1 mes Consentimiento informado por escrito y aprobación por parte de los organismos reguladores y del comité ético nacional/local Centro/país dispuesto y capaz de organizar una audiometría Posibilidad de cumplir los requisitos para el envío de material para la revisión central (radiología, patología y audiología) Para mujeres en edad fértil, es necesario obtener una prueba de embarazo negativa antes de iniciar el tratamiento en estudio Cualquier paciente en edad fértil debe acceder a utilizar un método anticonceptivo apropiado mientras dure el ensayo |
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E.4 | Principal exclusion criteria |
High risk hepatoblastoma Hepatocellular carcinoma Treatment starting more than 15 days from written biopsy report Abnormal renal function Any previous chemotherapy Identificador del archivo XML: EnC0NadSa9z49p98r3buLEOnYCI= Página 13 de 31 Recurrent disease Previous hypersensitivity to STS Patient unable to follow the protocol for any reason |
Hepatoblastoma de alto riesgo: Alfafetoproteína sérica (AFP) 100 µg//l Afectación tumoral en las 4 secciones hepáticas (PRETEXT IV) Criterios de PRETEXT adicionales: Enfermedad abdominal extrahepática Hemorragia intraperitoneal o ruptura tumoral Metástasis distantes, en cualquier lugar Metástasis en ganglios linfáticos Afectación de la vena portal principal Afectación de las tres venas hepáticas y/o la Vena Cava Inferior Carcinoma hepatocelular Inicio del tratamiento más de 15 días después del informe escrito de la biopsia Función renal anormal definida como TFG calculada < 75% del límite inferior de la normalidad para la edad en el momento del diagnóstico, que por encima de los 2 años de edad es < 60 ml/min/1,73 m2 Cualquier quimioterapia previa Enfermedad recurrente Hipersensibilidad previa a STS Paciente incapaz de seguir el protocolo por cualquier motivo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of Brock grade 1 hearing loss determined after end of trial treatment or at an age of at least 3.5 years, whichever is later |
Variables primarias Tasa de pérdida auditiva de grado 1 de Brock determinada una vez finalizado el tratamiento en ensayo o a una edad de al menos 3,5 años, lo que ocurra más tarde. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be reached when the last patient has completed his/her audiological testing or reached 3.5 years of age, whichever is later. Patients will then be followed up for the secondary endpoints according to national guidelines |
La variable primaria se alcanzará cuando el último paciente haya finalizado las pruebas audiológicas o haya alcanzado los 3,5 años de edad, lo que suceda más tarde. Luego se realizará el seguimiento de los pacientes para las variables secundarias según las directrices nacionales. |
|
E.5.2 | Secondary end point(s) |
Response to preoperative chemotherapy Complete resection Complete remission Event free survival (EFS) Overall survival (OS) Toxicity as graded by CTCAE v 3.0 Long-term renal clearance Feasibility of central audiology review |
Respuesta a la quimioterapia preoperatoria Resección completa Remisión completa Supervivencia libre de eventos (SLE) Supervivencia global (SG) Toxicidad según la escala CTCAE v 3.0 Aclaramiento renal a largo plazo Viabilidad de la revisión central de la audición |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Expected duration of recruitment period: 3.8 years |
Duración prevista del periodo de inclusión: 3,8 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 | No |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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 | 18 |
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 |
|
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 primary endpoint will be reached when the last patient has completed his/her audiological testing or reached 3.5 years of age, whichever is later. Patients will then be followed up for the secondary endpoints according to national guidelines |
La variable primaria se alcanzará cuando el último paciente haya finalizado las pruebas audiológicas o haya alcanzado los 3,5 años de edad, lo que suceda más tarde. Luego se realizará el seguimiento de los pacientes para las variables secundarias según las directrices nacionales. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |