E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2 positive breast cancer with progressive brain metastases after trastuzumab or lapatinib based therapy |
Cáncer de mama HER2 positivo con metástasis cerebrales progresivas después de haber recibido tratamiento a base de trastuzumab o lapatinib. |
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E.1.1.1 | Medical condition in easily understood language |
HER2 positive breast cancer with progressive brain lesions after a treatment with trastuzumab or lapatinib |
Cáncer de mama HER2 positivo con lesiones cerebrales progresivas después de haber recibido tratamiento con trastuzumab o lapatinib. |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006198 |
E.1.2 | Term | Breast cancer recurrent |
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 investigate the antitumour activity and safety of afatinib alone or in combination with vinorelbine versus investigator?s choice of treatment for the treatment of patients with HER2-positive breast cancer with progressive brain metastases after trastuzumab or lapatinib based therapy |
Investigar la actividad antitumoral y la seguridad de afatinib en monoterapia o en combinación con vinorelbina frente al tratamiento de elección del investigador para el tratamiento de pacientes con cáncer de mama HER2 positivo con metástasis cerebrales progresivas después de haber recibido tratamiento a base de trastuzumab o lapatinib. |
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E.2.2 | Secondary objectives of the trial |
Analysis of progression free survival and overall survival, |
Análisis de la supervivencia sin progresión y de la supervivencia global. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Histologically confirmed diagnosis of HER2-overexpressing breast cancer (HER2 status as previously assessed by local lab is acceptable). ? Documented CNS recurrence/progression during or after a HER2 inhibitor (i.e. Trastuzumab, Lapatinib) based therapy (no leptomeningeal carcinomatosis as the only site of CNS metastases) ? At least one measurable and progressive lesion in the CNS (?10 mm on T1-weighted, gadolinium-enhanced MRI) after prior systemic and/or radiation therapy. Measurable or non-measurable extra cranial metastases allowed. |
- Diagnóstico confirmado histológicamente de cáncer de mama con sobreexpresión de HER2 (se acepta un estado HER2 determinado previamente por un laboratorio local). - Recidiva/progresión en el SNC documentada (mediante diagnóstico por la imagen), durante o después de un tratamiento a base de un inhibidor de HER2 (trastuzumab o lapatinib) (no se permite la carcinomatosis leptomeníngea como única localización de metástasis en el SNC). - Al menos una lesión medible y progresiva en el SNC (? 10 mm en RMN realzada con gadolinio ponderada en T1) después de tratamiento sistémico y/o radioterapia previos. Se permiten metástasis extracraneales medibles o no medibles. |
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E.4 | Principal exclusion criteria |
Prior treatment with HER2-targeted treatment other than lapatinib and trastuzumab. ? Any other current malignancy or malignancy diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer). ? Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ?2 diarrhoea of any aetiology. ? History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension (investigator?s assessment), congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia in the investigator?s opinion. ? Cardiac left ventricular function by echocardiogram or MUGA scan with resting ejection fraction of less than 50%. |
- Tratamiento previo con un tratamiento anti HER2 distinto de lapatinib y trastuzumab. - Cualquier otro cáncer concomitante o diagnosticado en los últimos cinco (5) años (que no sean cáncer de piel no melanomatoso ni cáncer de cuello uterino in situ). - Trastornos gastrointestinales agudos recientes o crónicos significativos con diarrea como síntoma principal, por ejemplo, enfermedad de Crohn, malabsorción o diarrea de grado ? 2 de CTC, de cualquier etiología. - Antecedentes o presencia de anomalías cardiovasculares clínicamente significativas, como hipertensión no controlada (evaluación del investigador), insuficiencia cardíaca congestiva de clase 3 de la NYHA, angina inestable o arritmia mal controlada en opinión del investigador. - Función cardiaca ventricular izquierda por ecocardiografía o MUGA con fracción de eyección en reposo inferior al 50%. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Patient benefit at 12 weeks defined as absence of CNS disease progression according to RECIST 1.1 in addition to: no tumour related worsening of the neurological signs and symptoms (NSS), no tumour related increase in corticosteroid dosage and no progression of extra CNS disease. |
Beneficio para las pacientes a las 12 semanas, definido como ausencia de progresión de la enfermedad en el SNC según RECIST 1.1, además de: ausencia de empeoramiento asociado al tumor de los signos y síntomas neurológicos (SSN), ausencia de aumento de la dosis de corticosteroides para el tumor y ausencia de progresión de la enfermedad fuera del SNC. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessment every 6 weeks, including assessment by imaging and assessment of the neurological signs and symptoms and corticosteroid dosage |
Evaluación tumoral cada 6 semanas, incluyendo evaluación por imagen y evaluación de los signos y síntomas neurológicos y dosis de corticosteroides. |
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E.5.2 | Secondary end point(s) |
Progression-free survival (PFS) and overall survival |
? Supervivencia sin progresión ? Supervivencia global. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression-free survival (PFS) is the time from randomisation until the occurrence of disease progression or death, whichever comes first. Overall survival is the time from randomisation to death from any cause. |
Supervivencia sin progresión: Se define como el tiempo desde la fecha de la aleatorización hasta la fecha de progresión de la enfermedad o muerte, lo que ocurra antes. Supervivencia global: Se define como el tiempo desde la fecha de la aleatorización hasta la fecha de la muerte (con independencia de su causa). |
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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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
tratamiento de elección del investigador |
best investigator's choice of treatment |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
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 |
Korea, Republic of |
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 be terminated as soon as the last patient has completed the last additional follow-up visit documenting the disease progression or the start of new treatment or death. |
El ensayo finalizará tan pronto como la última paciente haya finalizado la última visita de seguimiento adicional en la que se documente progresión de la enfermedad, el inicio de un nuevo tratamiento o muerte. |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |