E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIB or IV EGFRm NSCLC with T790M positive mutation |
Estadio IIIB o metastásico (estadio IV) CPNM, con mutación positiva T790M del EGFRm |
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E.1.1.1 | Medical condition in easily understood language |
Specific type of lung cancer called "non-small cell lung cancer" NSCLC |
Tipo específico de cáncer de pulmón llamado "cáncer de pulmón no microcítico" (CPNM) |
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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 | 18.0 |
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) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
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 |
The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy. |
El objetivo principal de este estudio es evaluar la eficacia y la seguridad de la monoterapia con AZD9291 en la práctica real en pacientes adultos con cáncer de pulmón no microcítico (CPNM) con la mutación T790M del receptor del factor de crecimiento epidérmico (EGFR), avanzado/metastásico, que han recibido previamente tratamiento con un inhibidor de la tirosina cinasa del EGFR (EGFR-TKI). |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
No aplicable |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures. 2. Adults (according to each country regulations for age of majority). 3. Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation. 4. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment. 5. World Health Organization (WHO) performance status 0-2 6. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline. 7. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion 6. 8. Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential as defined below: a. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. b. Women under 50 years would be consider post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution. c. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. 9. Male patients must be willing to use barrier contraception, i.e., condoms. |
1. Otorgamiento del consentimiento informado por escrito, firmado y fechado, por el paciente o su representante legal, antes de cualquier procedimiento del estudio. 2. Adultos (de acuerdo a la legislación de cada país acerca de la mayoría de edad). 3. CPNM localmente avanzado (estadio IIIB) o metastásico (estadio IV) EGFRm, no susceptible de cirugía o radioterapia curativa, con confirmación de la presencia de la mutación T790M. 4. Tratamiento previo con un inhibidor de la tirosina cinasa del EGFR. También podrán haber recibido otras líneas de tratamiento. 5. Estado funcional de la Organización Mundial de la Salud (OMS) 0-2. 6. Reserva adecuada de médula ósea y función orgánica adecuada, tal como se desprende del hemograma completo y de la bioquímica en sangre y orina en el basal. 7. ECG en el basal sin las anomalías cardíacas recogidas en el criterio de exclusión nº 6. 8. Las mujeres potencialmente fértiles deben estar utilizando métodos anticonceptivos adecuados, no podrán estar amamantando y deberán presentar un resultado negativo de una prueba de embarazo antes del comienzo del tratamiento. En caso contrario, deberán mostrar evidencia de que no pueden concebir, tal como se define a continuación: a. Posmenopausia, definida como mujer de más de 50 años y amenorreica desde hace como mínimo 12 meses tras la suspensión de todo tratamiento hormonal exógeno. b. Las mujeres menores de 50 años podrían considerarse posmenopáusicas si han mostrado amenorrea durante 12 meses o más tras la suspensión de todo tratamiento hormonal exógeno y unos niveles de hormona luteinizante y de hormona foliculoestimulante en el rango posmenopáusico de la institución. c. Documentación de esterilización quirúrgica irreversible por histerectomía, ovariectomía bilateral o salpingectomía bilateral, pero no por ligadura tubárica. 9. Los pacientes varones deberán estar conformes en utilizar un método anticonceptivo de barrera, esto es, preservativo. |
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E.4 | Principal exclusion criteria |
1. Previous (within 6 months) or current treatment with AZD9291. 2. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4. 3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator?s opinion would significantly alter the risk/benefit balance. 4. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration. 5. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD. 6. Any of the following cardiac criteria: a. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia?s formula. b. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block). c. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events. 7. Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment. 8. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291. |
1. Tratamiento previo (en los 6 meses anteriores) o actual con AZD9291. 2. Tratamiento actual (o imposibilidad de su suspensión como mínimo una semana antes de la recepción de la primera dosis de AZD9291) con productos que se sabe que son potentes inhibidores o inductores del citocromo P450 (CYP) 3A4 (Apéndice C). 3. Cualquier signo de enfermedad sistémica severa o no controlada, tal como hipertensión no controlada, diátesis hemorrágica activa, infección activa (como hepatitis B y C y virus de la inmunodeficiencia humana), o afectación importante de la reserva de médula ósea o de función orgánica (como insuficiencia hepática o renal) que, en opinión del investigador, pudiera influir de manera significativa sobre el balance riesgo/beneficio. 4. Metástasis sintomáticas en sistema nervioso central (SNC) en un paciente neurológicamente inestable o que ha precisado dosis crecientes de corticosteroides para el control de los síntomas en SNC en el plazo de las 2 semanas previas al comienzo de la administración de AZD9291. 5. Antecedentes de neumopatía intersticial (NPI), NPI de origen farmacológico, neumonitis por radiación que precisó tratamiento con corticoides, o cualquier signo de NPI clínicamente activa. 6. Cualquiera de los siguientes criterios cardíacos: a. Valor medio del intervalo QT corregido (QTcF) > 470 ms utilizando la fórmula de Fridericia. b. Cualquier anomalía clínicamente importante del ritmo, la conducción o la morfología del ECG en reposo (por ejemplo, bloqueo completo de rama izquierda, bloqueo auriculoventricular de tercer grado, bloqueo auriculoventricular de segundo grado). c. Cualquier factor que pueda aumentar el riesgo de prolongación del QTc o el riesgo de arritmia. 7. Toda toxicidad no resuelta de un tratamiento previo que sea de Grado ?3 de los CTCAE en el momento de ir a comenzar el tratamiento. 8. Antecedentes de hipersensibilidad a los excipientes de AZD9291, o a fármacos de estructura química o familia similar a la de AZD9291. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), patient-reported lung cancer symptoms. |
Eficacia reportada por el Investigador (incluyendo la respuesta tumoral y la progresión de la enfermedad), la supervivencia global (SG), los síntomas del cáncer de pulmón reportados por los pacientes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and every 6 weeks from randomization until progression and 30 days post last dose. |
Al inicio del estudio y cada 6 semanas desde la aleatorización hasta la progresión y 30 días después de la última dosis. |
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E.5.2 | Secondary end point(s) |
Not applicable. |
No aplicable |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not applicable. |
No aplicable |
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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 | 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
| 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LVLS |
Última 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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |