E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcoma |
Rabdomiosarcoma, sarcoma de tejidos blandos no rabdomiosarcomatoso (incluyendo sarcoma sinovial, sarcoma de partes blandas alveolares y tumor desmoplásico de células pequeñas y redonda), Sarcoma de Ewing/ tumor neuroectodérmico primitivo periférico (PNET), Hepatoblastoma, Neuroblastoma (medible y evaluable) y osteosarcoma |
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E.1.1.1 | Medical condition in easily understood language |
Children, adolescents and young adults have one of the above tumors that have come back after treatment or is not responding to current treatment. |
Niños, adolescents y adultos jóvenes que tengan uno de los tumores antes mencionados que hayan vuelto a aparecer después del tratamiento o no responden al tratamiento actual. |
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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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10019825 |
E.1.2 | Term | Hepatoblastomas |
E.1.2 | System Organ Class | 100000005101 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029260 |
E.1.2 | Term | Neuroblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10041299 |
E.1.2 | Term | Soft tissue sarcomas |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031291 |
E.1.2 | Term | Osteosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10039023 |
E.1.2 | Term | Rhabdomyosarcomas |
E.1.2 | System Organ Class | 100000143528 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015560 |
E.1.2 | Term | Ewing's sarcoma |
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 determine the investigator- assessed objective response rate of pazopanib in children, adolescents and young adults (patients) with relapsed or refractory solid tumors of the following types (each defining a cohort): 1. rhabdomyosarcoma, 2. non-rhabdomyosarcomatous soft tissue sarcoma, or 3. Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET). |
Determinar la tasa de respuestas objetivas evaluada por el investigador de pazopanib en niños, adolescentes y jóvenes adultos (pacientes) con tumores sólidos refractarios o en recidiva de los siguientes tipos (cada uno define una cohorte): 1. rabdomiosarcoma, 2. sarcoma de tejidos blandos no rabdomiosarcomatoso, o 3. sarcoma de Ewing/tumor neuroectodérmico primitivo periférico (PNET) |
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E.2.2 | Secondary objectives of the trial |
To determine the investigator- assessed objective response rate of pazopanib in children, adolescents, and young adults (patients) 1 osteosarcoma, 2 neuroblastoma (measurable), 3 neuroblastoma (evaluable), or 4 hepatoblastoma •To further define and describe the toxicities of oral pazopanib •To further characterize the pharmacokinetics (PK) of pazopanib after administration of the powder suspension formulation •To determine progression free-survival •To determine the time to progression •To determine the therapeutic activity •To assess duration of response •To further examine the biologic relationship between tumor response and angiogenic cytokines. •To assess the genotype/phenotype relationships of VEGF in children with soft tissue sarcoma. •To further explore pazopanib pharmacokinetic/pharmacodynamic •To assess overall survival (OS) in patients with relapsed or refractory solid tumors per cohort |
Determinar la tasa de respuestas objetivas evaluada por el investigador de pazopanib en niños, adolescentes y jóvenes adultos (pacientes) 1 osteosarcoma, 2 neuroblastoma (medible), 3 neuroblastoma (evaluable), o 4 hepatoblastoma . Definir y describir mejor las toxicidades de pazopanib oral . Caracterizar mejor la farmacocinética (PK) de pazopanib después de la administración de la formulación de suspensión en polvo . Determinar la supervivencia libre de progression . Determinar el tiempo hasta la progression . Determinar la actividad terapéutica . Evaluar la duración de la respuesta . Evaluar la relación genotipo/fenotipo del factor de crecimiento endotelial vascular (VEGF) en niños con sarcoma de tejidos blandos. . Explorar mejor la relación farmacocinética/farmacodinámica de pazopanib . Evaluar la supervivencia global (SG) en pacientes con tumores sólidos refractarios o en recidiva por cohorte |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age: Patients must be at least 1 year and less than or equal to 18 years of age at the time of study entry. •Diagnosis: Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse. 1.Rhabdomyosarcoma 2.Non-rhabdomyosarcomatous Soft Tissue Sarcoma (including desmoplastic small round cell tumor) 3.Ewing Sarcoma/Peripheral PNET 4.Osteosarcoma 5.Neuroblastoma (Measurable) 6.Neuroblastoma (Evaluable) 7.Hepatoblastoma •Patient must have disease that has either relapsed or is refractory to prior therapy |
. Edad: El paciente deberá tener al menos 1 año y menos de o igual a 18 años en el momento de la inclusión en el estudio. . Diagnóstico: Los pacientes deberán disponer de verificación histológica de una de las neoplásicas malignas listadas a continuación en el diagnóstico original o en la recaída 1. Rabdomiosarcoma 2. Sarcoma de tejidos blandos no rabdomiosarcomatoso (incluyendo tumor desmoplásico de células pequeñas y redondas ) 3. Sarcoma de Ewing/ tumor neuroectodérmico primitivo periférico (PNET) 4. Osteosarcoma 5. Neuroblastoma (medible) 6. Neuroblastoma (evaluable) 7. Hepatoblastom . Los pacientes deberán presentar enfermedad en recidiva o refractaria a la terapia previa. |
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E.4 | Principal exclusion criteria |
•Pregnant or breast-feeding women are not eligible for this study •Concomitant Medications 1.Corticosteroids: Patients requiring corticosteroid who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible. 2.Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. 3.Anti-Cancer Agents or Radiation Therapy: Patients who are currently receiving other anti-cancer agents or radiation therapy are not eligible. 4.Anti-hypertensive: Patients who are currently receiving more than one anti-hypertensive medication (Grade 3) or whose blood pressure is not controlled (i.e. as defined in Section 3.2.8.) are not eligible for study enrollment. 5.Anti-coagulation: Patients must not be on therapeutic anticoagulation. ((Warfarin (coumadin®) and/or low molecular weight heparin are prohibited.) Prophylactic anticoagulation (ie intraluminal heparin) of venous or arterial access devices is allowed. 6.CYP3A4 Substrates and drugs causing QTc prolongation: Patients receiving drugs with a known risk of torsades de pointes are not eligible. See Appendices IIIA and IIIB and Section 4.8 for a list of enzyme inducing, enzyme inhibiting and other adversely interacting drugs and the appropriate washout periods required prior to study enrollment Note: This list includes the prohibition of grapefruit juice for 14 days prior to enrollment and while receiving pazopanib. 7.Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment •Patients who are unable to swallow tablets or liquid are not eligible. Pazopanib cannot be administered via NG tube or G-tube |
. Las mujeres embarazadas o lactantes no son elegibles para este studio . Medicaciones concomitants 1. Corticosteroides: Los pacientes que precisen corticosteroides que no hayan mantenido una dosis estable o reducida de corticosteroides durante los 7 días antes de la inclusión, no son elegibles. 2. Fármacos en investigación: Los pacientes que estén recibiendo actualmente otro fármaco en investigación no son elegibles. 3. Agentes antineoplásicos o radioterapia: Los pacientes que estén recibiendo actualmente otros agentes antineoplásicos o radioterapia no son elegibles. 4. Medicación antihipertensiva: Los pacientes que estén recibiendo actualmente más de una medicación antihipertensiva (grado 3) o cuya presión arterial no esté controlada (es decir, como se define en el Apartado 3.2.8) no son elegibles para inclusión en el estudio. 5. Anticoagulación: Los pacientes no deberán recibir anticoagulación terapéutica. (La warfarina (coumadin®) y o la heparina de bajo peso molecular están prohibidas). Se permite anticoagulación profiláctica (es decir, heparina intraluminal) de dispositivo de acceso arterial o venoso. 6. Sustratos de CYP3A4 y fármacos que causen prolongación del QTc: Los pacientes que reciban fármacos con un riesgo conocido de torsades de pointes no son elegibles. Véase Suplemento IIIA y IIIB y Apartado 4.8 para una lista de inductores de enzimas, inhibidores de enzimas y de otros fármacos que interactúan negativamente y los periodos de lavado apropiados requeridos antes de la inclusión en el estudio. Nota: Esta lista incluye la prohibición del consumo de zumo de pomelo durante 14 días antes de la inclusión y mientras estén recibiendo pazopanib. 7. Terapia sustitutiva tiroidea: Los pacientes que precisen terapia sustitutiva tiroidea no son elegibles si no han estado recibiendo una dosis de sustitución estable durante por lo menos 4 semanas antes de la inclusión en el estudio . Los pacientes que no puedan tragar comprimidos o líquidos no son elegibles. Pazopanib no puede administrarse a través de sonda nasogástrica o sonda gástrica |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) for the 3 tumor types of primary interest |
Tasa de respuesta objetiva (ORR) para los 3 tipos de tumors de interés primario |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary analysis will be performed 20 weeks after LPFV in the 3 cohorts of primary interest |
Un primer analisis se realizará 20 semanas despues del LPFV en los 3 cohorts de interés primario. |
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E.5.2 | Secondary end point(s) |
ORR for the 4 tumor types of secondary interest Progression-free survival (PFS) Overall survival (OS) Time to progression (TTP) Safety measures Duration of response (DoR) |
ORR para los 4 tipos de tumores de interes secundario supervivencia libre de progression (PFS). Supervivencia global (OS) tiempo hasta la progression (TTP) Medidas de seguridad Duración de la respuesta (DoR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Primary analysis will be performed 20 weeks after LPFV in the 3 cohorts of primary interest |
El análisis principal se realizará 20 semanas despues de la última visita del ultimo paciente en los 3 cohorts de interés principal |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | 7 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Canada |
Czech Republic |
France |
Hungary |
Italy |
Slovakia |
Spain |
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
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One year from the date of the last patient’s first visit. |
Un año desde la fecha de la primera visita del último paciente. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |