E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ewing's Sarcoma Family of Tumours |
Sarcoma de Ewing |
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E.1.1.1 | Medical condition in easily understood language |
Ewing's Sarcoma Family of Tumours |
Sarcoma de Ewing |
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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 | 17.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the induction/consolidation chemotherapy randomisation (R1) is to compare the VIDE strategy (VIDE induction and VAI/VAC consolidation) with the VDC/IE strategy (compressed VDC/IE induction and IE/VC consolidation). The event-free survival (EFS) of the two chemotherapy regimens will be compared, and also the relative toxicity experienced by patients both before and after local control of the primary tumour |
El objetivo de la randomización de la quimioterapia de inducción/consolidación (R1) es comparar la estrategia VIDE (inducción VIDE y consolidación VAI/VAC) con la estrategia VDC/IE (inducción VDC/IE comprimida y consolidación IE/VC). Se comparará la supervivencia libre de eventos (SLE) de los dos regímenes quimioterápicos, y también la toxicidad experimentada por los pacientes antes y después del control local del tumor primario |
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E.2.2 | Secondary objectives of the trial |
The objective of the zoledronic acid randomisation (R2) is to determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome in patients with localised ESFT or with pulmonary and/or pleural metastases only at diagnosis. |
El objetivo de la randomización del ácido zoledrónico (R2) es determinar si la adición del ácido zoledrónico a la quimioterapia de consolidación, tal y como se asignó en la R1, está asociada con una mejora en el resultado clínico en pacientes con sarcoma de Ewing localizado o con metástasis pulmonares y/o pleurales sólo en el diagnóstico |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The biological studies associated with this trial are incorporated into the Euro Ewing 2012 protocol (version 2.0, dated 3rd March 2014). The objective of the biological studies is to identify informative prognostic biomarkers for assessment of disease status and response at diagnosis and throughout the disease course. Whether they are predictive of response to therapy and may be used to improve stratification of patients and whether they might predict those patients that may not tolerate a particular therapy will be explored. |
Los estudios biológicos asociados a este ensayo son incorporados en el protocolo Euro Ewing 2012 (versión 2.0, del 3 de Marzo 2014). El objetivo de los estudios biológicos es identificar biomarcadores pronósticos informativos para la evaluación del estado de la enfermedad y la respuesta en el diagnóstico y en el curso de la enfermedad. Se estudiará si son predictivos de la respuesta al tratamiento y se pueden usar para mejorar la estratificación de los pacientes y predecir aquellos pacientes que puedan no tolerar una terapia en particular. |
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E.3 | Principal inclusion criteria |
? Histologically confirmed ESFT of bone or soft tissue ? Localised or pulmonary and/or pleural metastatic disease ? Age >2 years and <50 years (from second birthday to 49 years 364 days) at the date of diagnostic biopsy ? Randomisation ?45 days after diagnostic biopsy/surgery ? Patient assessed as medically fit to receive the treatment in either of the R1 treatment arms ? No prior treatment for ESFT other than surgery ? Documented negative pregnancy test for female patients of childbearing potential ? Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where applicable ? Written informed consent from the patient and/or the parent/legal guardian |
? Sarcoma de Ewing en el hueso o tejido blando confirmado histológicamente ? Enfermedad localizada o metastásica pulmonar y/o pleural ? Edad ?2 años y ?50 años (desde el segundo cumpleaños hasta 49 años y 364 días) en la fecha de la biopsia diagnóstica ? Randomización ? 45 días después de la biopsia/cirugía de diagnóstico ? Paciente evaluado como clínicamente adecuado para recibir el tratamiento en cualquiera de los brazos de tratamiento R1 ? Ausencia de tratamiento anterior para el Sarcoma de Ewing excepto cirugía ? Prueba de embarazo negativa documentada para mujeres en edad fértil ? Pacientes que acceden al uso de métodos anticonceptivos durante el tratamiento y durante 12 meses después del último tratamiento del ensayo (mujeres) o 6 meses después del último tratamiento del ensayo (hombres), donde aplique ? Consentimiento informado escrito del paciente y/o padre/tutor legal |
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E.4 | Principal exclusion criteria |
? Extrapulmonary metastatic disease ? Contra-indication to the treatment in either of the R1 treatment arms ? Second malignancy ? Pregnant or breastfeeding women ? Follow-up not possible due to social, geographic or psychological reasons |
? Enfermedad metastásica extrapulmonar ? Contraindicación del tratamiento de algún brazo de la R1 ? Segunda malignidad ? Mujeres embarazadas o lactantes ? Cuando no sea posible el seguimiento debido a razones sociales, geográficas o psicológicas |
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-free survival (EFS) |
Supervivencia libre de eventos (SLE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For each randomisation, EFS is defined as the time from randomisation to first event, where an event is progression without complete remission, recurrence (following complete remission), diagnosis of second malignancy or death. Patients who have not had an event will be censored at their last follow-up date. Patients lost to follow-up without an event will be censored at the date of their last consultation. |
Para cada randomización, supervivencia libre de eventos (SLE) se define como el tiempo desde la randomización al primer evento, donde un evento es progresión sin remisión completa, recidiva (después de remisión completa), diagnóstico de segunda malignidad o muerte. Los pacientes que no han tenido ningún evento serán censurados el día de su último seguimiento. Los pacientes perdidos para seguimiento sin ningún evento serán censurados el día de su última consulta. |
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E.5.2 | Secondary end point(s) |
? Overall Survival (OS) ? Adverse events and toxicity, defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 ? Histological response of the primary tumour to induction chemotherapy if surgery is performed as local control. ? Primary tumour and lung and/or pleural metastases response ? Achievement of local control at the end of treatment ? Growth parameters and jaw osteonecrosis (R2 only) |
? Supervivencia global (SG) ? Efectos adversos y toxicidad, utilizando la terminología NCI-CTCAE v4.0. ? Respuesta histológica del tumor primario a la quimioterapia de inducción si la cirugía es llevada a cabo como control local ? Respuesta del tumor primario y de las metástasis pulmonares y/o pleurales ? Logro del control local al final del tratamiento ? Parámetros de crecimiento y osteonecrosis mandibular (sólo R2) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
? Overall Survival (OS) ? evaluated continually ? Adverse events and toxicity ? evaluated after each course of chemotherapy, or as reported ? Histological response of the primary tumour to induction chemotherapy if surgery is performed as local control ? evaluated at the time of surgery following induction chemotherapy ? Primary tumour and lung and/or pleural metastases response-evaluated after 2 cycles (Arm A), or 3 cycles (Arm B). ? Achievement of local control at the end of treatment ? evaluated at the time of surgery following induction chemotherapy or at the end of treatment or six months after the end of treatment ? Growth parameters (R2 only)? evaluated at baseline, end of treatment and at follow up ? Jaw osteonecrosis (R2 only)? evaluated at the end of or during treatment |
?SG-evaluada continuamente ?Efectos adversos y toxicidad-evaluado después de cada curso de quimioterapia, o como sea informado ?Respuesta histológica del tumor primario a la quimioterapia de inducción si la cirugía es llevada a cabo como control local-evaluada en el momento de la cirugía que sigue a la quimioterap de inducción ?Respuesta del tumor primario de las metástasis pulmonares y/o pleurales-evaluada después de 2 ciclos (Brazo A) o 3 (Brazo B) ?Logro del control local al final del tratamiento-evaluado en el momento de la cirugía que sigue a la inducción o al final del tratamiento o 6 meses después ?Parámetros de crecimiento (sólo R2)-evaluado en el basal, al final del tratamiento y en el seguimiento ?Osteonecrosis mandibular (sólo R2)-evaluado al final o durante el tratamiento |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 |
France |
Ireland |
Israel |
Spain |
United Kingdom |
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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The trial will remain open until all trial objectives have been met. |
El ensayo permanecerá abierto hasta que todos los objetivos del ensayo se hayan alcanzado |
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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 | 11 |
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 | 11 |
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 |