E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced stage NSCLC, harbouring HER2 exon 20 mutations |
CPNM en estadio avanzado con mutaciones del exón 20 de HER2 |
|
E.1.1.1 | Medical condition in easily understood language |
A type of lung cancer called ?non small cell lung cancer (NSCLC)? that has recently relapsed. The cancer is harbouring a specific gene mutation (change) in the human epidermal growth factor 2 (HER2) |
Tipo de cáncer de pulmón llamado "cáncer de pulmón no microcítico (CPNM)" que ha recaído recientemente. Alberga una mutación genética específica en el factor de crecimiento epidérmico humano 2 (HER2) |
|
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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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 evaluate the ability of afatinib to control disease in pretreated patients with advanced NSCLC harbouring HER2 exon 20 mutations. |
Evaluar la capacidad de afatinib para controlar la enfermedad en pacientes pretratados con CPNM avanzado que albergan mutaciones del exón 20 de HER2. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate secondary measures of clinical efficacy including progression free survival (PFS), objective response rate (ORR) and overall survival (OS). - To assess the safety and the tolerability of the treatment. |
- Evaluar las variables secundarias de eficacia clínica, incluyendo la supervivencia libre de progresión (SLP), la tasa de respuesta objetiva y la supervivencia global. - Evaluar la seguridad y la tolerabilidad del tratamiento. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically or cytologically confirmed, non-predominant squamous subtype, stage IIIB (non amenable to curative-intent multimodal treatment) or IV NSCLC, according to 7th TNM classification - Tumour is platinum-refractory - Measurable or evaluable disease (according to RECIST 1.1 criteria) - Locally documented HER2 mutation - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Life expectancy >3 months - Adequate haematological, renal and hepatic function - Effective contraception, no pregnancy |
- CPNM de subtipo escamoso no predominante, confirmado por análisis histológico o citológico, en estadio IIIB (no susceptible de tratamiento multimodal con intención curativa) o IV, según la 7ª clasificación TNM - Tumor refractario al platino - Enfermedad mensurable o evaluable (según criterios RECIST 1.1) - Mutación de HER2 documentada localmente - Categoría funcional 0-2 del Grupo Cooperativo de Oncología del Este (ECOG) - Esperanza de vida > 3 meses - Función hematológicas, renal y hepática adecuada - Anticoncepción eficaz, ausencia de embarazo |
|
E.4 | Principal exclusion criteria |
- Mixed small-cell and non-small-cell histologic features - Uncontrolled lepto-meningeal metastatic disease - Previous treatment with HER2 targeted antibody or tyrosine kinase inhibitor - Any previous (in the past 3 years) or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast - History or presence of clinically relevant cardiovascular abnormalities - Other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient?s capacity to participate in the trial - Interstitial lung disease or pulmonary fibrosis - Any concurrent systemic anticancer therapy |
- Características histológicas microcíticas y no microcíticas combinadas - Metástasis leptomeníngeas no controladas - Tratamiento previo con anticuerpos anti-HER2 selectivos o inhibidores de la tirosina-cinasa - Cualquier enfermedad maligna previa (en los últimos 3 años) o concomitante, A EXCEPCIÓN de un carcinoma basocelular o epidermoide de la piel tratado adecuadamente, un carcinoma in situ del cuello uterino de la vejiga o un carcinoma ductal in situ de la mama. - Antecedentes o presencia de alteraciones cardiovasculares con repercusión clínica - Otras enfermedades o trastornos clínicos graves, como por ejemplo infección activa no controlada y cualquier proceso médico grave que pueda mermar la capacidad del paciente para participar en el estudio - Enfermedad pulmonar intersticial o fibrosis pulmonar - Cualquier tratamiento anticanceroso simultáneo por vía sistémica |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Disease control defined as complete or partial response, or disease stabilisation lasting at least 12 weeks. |
Control de la enfermedad definido como respuesta completa o parcial, o estabilización de la enfermedad a las 12 semanas. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Complete or partial response, or disease stabilisation lasting at least 12 weeks. |
Respuesta completa o parcial, o estabilización de la enfermedad a las 12 semanas. |
|
E.5.2 | Secondary end point(s) |
- Progression-free survival by RECIST 1.1 - Objective response determined by RECIST 1.1 - Overall survival - Adverse events graded according to CTCAE V4.0 |
- Supervivencia sin progresión según RECIST 1.1 - Respuesta objetiva determinada según RECIST 1.1 - Supervivencia global - Acontecimientos adversos graduados según CTCAE V4.0 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Progression-free survival: Time from the date of enrolment until documented progression or death, if progression is not documented. Censoring will occur at the last tumour assessment only if patient is lost to follow-up. - Objective response: Best overall response (CR or PR) across all assessment time-points during the period from enrolment to termination of trial treatment. Objective response to afatinib treatment will be determined using RECIST 1.1 criteria. - Overall survival: Time from the date of enrolment until death from any cause. Censoring will occur at the last follow-up date. - Toxicity: Adverse events classified according to NCI CTCAE version 4. |
- Supervivencia libre de progresión: Tiempo desde la fecha de inclusión hasta la documentada progresión o muerte, si la progresión no está documentada. La censura ocurrirá en la última evaluación del tumor solamente si el paciente se perdió durante el seguimiento. - Respuesta Objetiva: Mejor respuesta global (RC o RP) en todos los de tiempo de evaluación durante el período de inclusión para la terminación del tratamiento del ensayo. La respuesta objetiva al tratamiento con afatinib se determinará utilizando RECIST 1.1 criterios. - Supervivencia global: Tiempo desde la fecha de inclusión hasta la muerte por cualquier causa. La censura ocurrirá en la última fecha de seguimiento. - Toxicidad: Los eventos adversos se clasificarán según NCI CTCAE versión 4. |
|
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 | 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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 total trial duration will be approximately 40 months including a 6 months start-up period, 24 months accrual, 6 months follow-up after inclusion of the last patient, and 4 months for preparation of the final trial report. |
La duración total del ensayo será de aproximadamente 40 meses, incluyendo un período de puesta en marcha 6 meses, 24 meses de reclutamiento, 6 meses de seguimiento después de la inclusión del último paciente, y 4 meses para la elaboración del informe final del ensayo. |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |