E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alveolar soft part sarcoma |
Sarcoma alveolar de partes blandas |
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E.1.1.1 | Medical condition in easily understood language |
Alveolar sarcoma cancer type of soft parts of the body |
Tipo de cáncer sarcoma alveolar de las partes blandas del cuerpo |
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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 | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001883 |
E.1.2 | Term | Alveolar soft part sarcomas |
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 |
To measure the percentage change in the size of patient's tumours after 24 weeks of treatment (or at the time of disease progression if this is sooner) in patients taking cediranib, compared to those taking a placebo. |
Medir el porcentaje de cambio de tamaño de los tumores de los pacientes después de 24 semanas de tratamiento (o en el momento de la progresión de la enfermedad si es antes) en pacientes que toman cediranib, comparado con aquellos que toman placebo. |
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E.2.2 | Secondary objectives of the trial |
? To measure the response rate of patients after 24 weeks of treatment (this is the percentage of patients having a complete response to treatment, a partial response to treatment or stable disease. The different types of 'response' described are defined by specific criteria in a standard document called RECIST v1.1). Also, to measure the best response seen and the best reduction in tumour size for each patient. ? To measure progression-free survival (this is the length of time the patient's cancer does not get worse); also to measure the percentage of patients who are alive and progression-free at 12 months (this is the percentage of patients who at 12 months are still alive and their cancer has not got worse). ? To measure the overall survival of patients, which measures how long each patient survives, regardless of the stage of their disease. ? To evaluate how safe and how well tolerated cediranib is in patients with ASPS |
? Medir índice de respuesta después de 24 semanas de tratamiento (porcentaje de pacientes que tienen una respuesta completa al tratamiento, respuesta parcial al tratamiento o enfermedad estable. Los diferentes tipos de "respuesta" se definen en un documento estándar llamado RECIST v1.1). También, medir la mejor respuesta observada y la mejor reducción en tamaño de tumor para cada paciente. ? Medir supervivencia libre de progresión (este es el periodo de tiempo en el que el cáncer del paciente no empeora); también medir el porcentaje de pacientes que están vivos y libres de progresión a los 12 meses (este es el porcentaje de pacientes que a los 12 meses siguen vivos y su cáncer no ha empeorado). ? Medir la supervivencia global de los pacientes, que mide cuánto tiempo sobrevive el paciente, independientemente de la fase de su enfermedad. ? Evaluar la seguridad y tolerancia del cediranib en pacientes con sarcoma alveolar de partes blandas. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically confirmed diagnosis of ASPS 2.Age 16 years and older 3.Availability of archived tissue blocks or unstained slides to enable confirmation of t(X;17) translocation 4.ECOG Performance Status of 0-1 5.Life expectancy of >12 weeks 6.Progressive disease within 6 months prior to randomisation 7.Measurable metastatic disease using RECISTv1.1, i.e. at least one lesion 10 mm in diameter (15 mm in short axis for nodal lesions) assessable by spiral CT (or MRI for brain metastases). 8.Patients with brain metastases are permitted provided disease is controlled with a stable dose of corticosteroid and/or non-enzyme inducing anticonvulsant 9.The capacity to understand the patient information sheet and ability to provide written informed consent 10.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures 11.Able to swallow and retain oral medication |
1.Diagnóstico histológico confirmado de sarcoma alveolar de partes blandas 2.Edad 16 años o más 3.Disponibilidad de bloques de tejido archivado o unstained slides para confirmación de traslocación t(X;17) 4.ECOG Performance Status: 0-1 5.Esperanza de vida >12 semanas 6.Enfermedad progresiva en 6 meses antes de randomización 7.Enfermedad metastásica medible según RECISTv1.1, ej: al menos una lesión de 10 mm de diámetro (15 mm en eje corto para lesiones nodales) evaluable por TAC espiral (o RMN para metástasis cerebral). 8.Pacientes con metástasis se permiten si la enfermedad está controlada con una dosis estable de corticoesteroide y/o no-enzima induciendo anticonvulsivante 9.La capacidad para entender la hoja de información al paciente y la habilidad para proporcionar el consentimiento informado escrito 10.Voluntad y habilidad para cumplir con las visitas programadas, planes de tratamiento, pruebas de laboratorio y otros procedimientos del estudio 11.Capacidad de tragar y retener medicación oral |
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E.4 | Principal exclusion criteria |
1.Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count ?1.5 x 109/L or platelet count ?100 x 109/L. 2.Serum bilirubin ? 1.5 x ULN (unless Gilbert?s syndrome). 3.ALT or AST ? 2.5 x ULN. If liver metastases are present, ALT or AST > 5 x ULN. 4.Serum creatinine > 1.5 x ULN or a creatinine clearance (calculated or measured) of ? 50mL/min calculated. 5.Greater than +1 proteinuria unless urinary protein < 1.5g in a 24 hr period or protein/creatinine ratio < 1.5. 6.History of significant gastrointestinal impairment, as judged by the Investigator,that would significantly affect the absorption of cediranib. 7.Patients with a history of poorly controlled hypertension with resting blood pressure >150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy. 8.Any evidence of severe or uncontrolled co-morbidities e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, or active and uncontrolled infection. 9.Evidence of prolonged QTc >480 msec (using Bazetts correction, for which the formula is: QTc = QT/?RR) or history of familial long QT syndrome. 10.Significant recent haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks). 11.Major thoracic or abdominal surgery in the 14 days prior to entry into the study, or a surgical incision that is not fully healed. 12.Pregnant or breast-feeding women; women of childbearing potential with a positive pregnancy test prior to receiving study medication; women the intention of pregnancy during study treatment; women of child bearing potential unwilling to have a urine or serum pregnancy test prior to study entry (even if surgically sterilised). 13.Men and women of childbearing potential unwilling to use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) for the duration of the study and should continue such precautions for 2 weeks after receiving the last study treatment. 14.History of anticancer (including investigational, non-registered) treatment in the four weeks prior to first dose of cediranib, with the exception of palliative radiotherapy for symptom control. 15.Known hypersensitivity to cediranib or any of its excipients. 16.History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion. 17.Other concomitant anti-cancer therapy (including LHRH agonists) except steroids. 18.Recent history of thrombosis. 19.Patients with brain metastases if they are symptomatic requiring increasing steroids in the previous six weeks to study entry or those with evidence of recent and/or active bleeding, or those causing uncontrolled seizures. |
1.Reserva de médula ósea inadecuada con un número absoluto de neutrófilos ?1.5 x 109/L o plaquetas ?100 x 109/L 2.Bilirrubina en suero ? 1.5 x ULN (a excepción de síndrome Gilbert) 3.ALT o AST ? 2.5 x ULN. Si metástasis de hígado, ALT o AST > 5 x ULN 4.Creatinina en suero > 1.5 x ULN or creatinina clearance (calculada o medida) de ? 50mL/min calculada 5.Proteinuria mayor que +1 a menos que proteína urinaria < 1.5g en un periodo de 24h o proteína/creatinina ratio < 1.5. 6.Historial de discapacidad gastrointestinal significativa, a juicio del investigador, que afectaría significativamente la absorción de cediranib 7.Pacientes con historia de hipertensión pobremente controlada con presión sanguínea en reposo >150/100 mmHg en la presencia o ausencia de un régimen estable de terapia anti-hipertensión 8.Cualquier evidencia de co-morbidades severas o no controladas, como enfermedad respiratoria, cardiaca, hepática o renal inestable o no compensada, o infección activa y no controlada 9.Evidencia de QTc prolongado >480 msec (usando corrección Bazetts, cuya fórmula es: QTc = QT/?RR) o historia de síndrome QT largo familiar 10.Hemorragia reciente significativa (>30mL sangrado/episodio en 3 meses previos) o hemoptisis (>5mL sangre fresca en 4 semanas previas) 11.Cirugías torácicas o abdominales importantes en los 14 días previos a la entrada en el estudio, o incisión quirúrgica no completamente sanada 12.Mujeres embarazadas o en lactancia; test de embarazo previo a recibir medicación; con intenciones de embarazo durante tratamiento; mujeres no dispuestas a hacer un test de embarazo de orina o suero antes de la entrada en el estudio (incluso con esterilización quirúrgica). 13.Hombres y mujeres en edad fértil no dispuestos a usar medidas de control adecuadas (abstinencia, anticonceptivos orales, dispositivo intrauterino, método de barrera con espermicida, anticonceptivos implantables o inyectables o esterilización quirúrgica) por la duración del estudio, y debería continuar las precauciones por 2 semanas después de recibir el último tratamiento del estudio. 14.Historia de tratamiento antineoplásico (incluyendo investigacional, no registrado) en las cuatro semanas anteriores a la primera dosis de cediranib, con la excepción de radioterapia paliativa para control de síntomas. 15.Hipersensibilidad conocida a cediranib o a cualquiera de sus excipientes. 16.Historia de otras malignidades (excepto para carcinoma espinocelular o carcinoma in situ adecuadamente tratado en basal) en 5 años, a menos que paciente ha estado libre de enfermedad por 2 años y existe diagnóstico de tejido del cáncer primario de interés de una lesión diana. 17.Otra terapia antineoplásica concomitante (incluyendo agonistas LHRH) excepto esteroides. 18.Historia reciente de trombosis. 19.Pacientes con metástasis cerebrales si son sintomáticas requiriendo esteroides en incremento en las seis semanas previas a la entrada del estudio o aquellos con evidencia de sangrado reciente y/o activo, o aquellos causantes de convulsiones descontroladas. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy of cediranib in the treatment of ASPS by measuring the percentage change in tumour size from randomisation to week 24 (or progression if sooner) compared to treatment with placebo. |
Evaluar la eficacia de cediranib en el tratamiento del sarcoma alveolar de partes blandas midiendo el porcentaje de cambio en tamaño de tumor desde randomización a la semana 24 (o progresión si ocurre antes) comparado con el tratamiento con placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 24 from randomisation |
Semana 24 desde randomización |
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E.5.2 | Secondary end point(s) |
1) To measure the response rate of patients after 24 weeks of treatment (this is the percentage of patients having a complete response to treatment, a partial response to treatment or stable disease. The different types of 'response' described are defined by specific criteria in a standard document called RECIST v1.1). Also, to measure the best response seen and the best reduction in tumour size for each patient. 2) To measure progression-free survival (this is the length of time the patient's cancer does not get worse); also to measure the percentage of patients who are alive and progression-free at 12 months (this is the percentage of patients who at 12 months are still alive and their cancer has not got worse). 3) To measure the overall survival of patients, which measures how long each patient survives, regardless of the stage of their disease. 4) To evaluate how safe and how well tolerated cediranib is in patients with ASPS |
1) Medir índice de respuesta después de 24 semanas de tratamiento (porcentaje de pacientes que tienen una respuesta completa al tratamiento, respuesta parcial al tratamiento o enfermedad estable. Los diferentes tipos de "respuesta" se definen en un documento estándar llamado RECIST v1.1). También, medir la mejor respuesta observada y la mejor reducción en tamaño de tumor para cada paciente. 2) Medir supervivencia libre de progresión (este es el periodo de tiempo en el que el cáncer del paciente no empeora); también medir el porcentaje de pacientes que están vivos y libres de progresión a los 12 meses (este es el porcentaje de pacientes que a los 12 meses siguen vivos y su cáncer no ha empeorado). 3) Medir la supervivencia global de los pacientes, que mide cuánto tiempo sobrevive el paciente, independientemente de la fase de su enfermedad. 4) Evaluar la seguridad y tolerancia del cediranib en pacientes con sarcoma alveolar de partes blandas. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 24 weeks 2) 12 months 3) Long term 4) Different stages of the study |
1) 24 semanas 2) 12 meses 3) Largo plazo 4) Diferentes fases del estudio |
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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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
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 |
Las primeras 24 semanas son doble ciego, después todos los pacientes pasan a cediranib (open label). |
First 24 weeks are double blind, then all patients cross over to open label cediranib. |
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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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
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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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The end of the interventional period of the trial is defined as 30 days after the last trial participant receives the last dose of the investigational medicinal product. However patients will continue to be followed up for survival after this time point. |
El final del periodo de intervención del ensayo se define como 30 días después de que el último participante del ensayo reciba la última dosis del producto medicinal en investigación. Sin embargo los pacientes serán seguidos para supervivencia posteriormente. |
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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 | 6 |
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 | 6 |
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 |