E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with locally advanced or metastatic (stage IIIb-IVb) EGFRm (exon 19 deletion or exon 21 L858R) NSCLC with T790M resistance mutation at progression on prior EGFR TKI therapy |
Los pacientes con CPNM con EGFRm (exon 19 deleción o exón 21 L858R) localmente avanzado o metastásico (etapa IIIb-IVb) con mutación de resistencia a T790M con progresión en la terapia previa con TKI de EGFR |
|
E.1.1.1 | Medical condition in easily understood language |
Patients who already received EGFR Inhibitor therapy against their lung cancer that has progressed or spread to other parts of the body and that has specific changes in the EGFR gene |
Los pacientes que ya recibieron tratamiento con inhibidores de EGFR que ha progresado o hayan progresado a otras partes del cuerpo y que tiene cambios específicos en el gen de EGFR |
|
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 | 19.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 assess the efficacy of the combination of osimertinib and bevacizumab versus osimertinib alone in terms of progression-free survival (PFS) assessed by RECIST 1.1. |
Evaluar la eficacia de la combinación de osimertinib y bevacizumab versus osimertinib solo en términos de supervivencia libre de progresión (PFS) evaluada por RECIST 1.1. |
|
E.2.2 | Secondary objectives of the trial |
To compare short and long term clinical efficacy outcomes as well as tolerability of the two treatments. |
Comparar los resultados de eficacia clínica a corto y largo plazo, así como la tolerabilidad de los dos tratamientos. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or IVa/IVb according to 8th TNM classification, after progression following prior EGFR TKI (erlotinib, gefitinib, dacomitinib or afatinib) therapy as the most recent treatment regimen. • Pathological diagnosis of predominantly non-squamous NSCLC. • Maximum of one line of previous platinum based chemotherapy. • Histological or cytological confirmation of EGFRm (exon19 deletion or exon 21 L858R). • Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent EGFR TKI regimen. • Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE tumor material is not yet fully depleted) after disease progression on the most recent EGFR TKI treatment available for central confirmation of T790M. • Measurable or evaluable disease • Adequate haematological, renal and liver function • Performance status 0-2 |
- Cancer de pulmón no microcítico, estadio IIIb / IIIc (no susceptible de terapia radical) o IVa / IVb de acuerdo con la 8ª clasificación TNM, después de la progresión después del tratamiento con TKI EGFR anterior (erlotinib, gefitinib, dacomitinib o afatinib) como el tratamiento más reciente. • Diagnóstico patológico de NSCLC predominantemente no escamoso. • Máximo de una línea de quimioterapia previa basada en platino. • Confirmación histológica o citológica de EGFRm (exon19 deleción o exón 21 L858R). • Mutación de T790M confirmada localmente determinada a partir de la biopsia (preferida) o del ADN circulante del tumor, documentado en tejido, plasma o suero después de la progresión de la enfermedad en el régimen de TKI EGFR más reciente. • El tejido o la citología de plasma, suero y tumor (preferente) (si se tomó biopsia y el material tumoral de FFPE aún no se ha agotado completamente) después de la progresión de la enfermedad en el tratamiento con TKI EGFR más reciente disponible para la confirmación central de T790M. • Enfermedad mensurable o evaluable • Función hematológica, renal y hepática adecuada • ECOG 0-2 |
|
E.4 | Principal exclusion criteria |
Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small cell lung cancer (SCLC) component. • Symptomatic or active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. • Previous treatment with osimertinib and/or bevacizumab • Patients currently receiving medications or herbal supplements known to be potent CYP3A4 inducers • Any unresolved toxicities from prior therapy greater than CTCAE V 4.0 grade 1 • Cualquier toxicidad no resuelta de terapia previa mayor que CTCAE V 4.0 grado 1 |
Pacientes con NSCLC mixto con predominio de cáncer de células escamosas, o con cualquier componente de cáncer de pulmón de células pequeñas (SCLC). • Metástasis del sistema nervioso central sintomáticas o activas, según lo indicado por síntomas clínicos, edema cerebral y / o crecimiento progresivo. • Tratamiento previo con osimertinib y / o bevacizumab • Los pacientes que actualmente reciben medicamentos o suplementos de hierbas que se sabe son potentes inductores de CYP3A4 • Cualquier toxicidad no resuelta de terapia previa mayor que CTCAE V 4.0 grado 1 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) based on RECIST 1.1 criteria |
Supervivencia libre de progresión basado en los criterios RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from the date of randomisation until documented progression or death, if progression is not documented |
Tiempo desde la fecha de la asignación al azar hasta progresión documentada o muerte, si la progresión no está documentada |
|
E.5.2 | Secondary end point(s) |
• Objective Response (OR), based on RECIST 1.1 criteria • Disease control, defined as complete or partial response, or disease stabilisation, confirmed at subsequent radiological assessment •Adverse events graded by CTCAE V4.0 •Overall survival (OS) |
Respuesta Objetiva (OR), basada en criterios RECIST 1.1 • Control de la enfermedad, definido como respuesta completa o parcial, o estabilización de la enfermedad, confirmado en evaluación • Eventos adversos clasificados por CTCAE V4.0 • Supervivencia general (SO) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• OR : across all assessment time-points during the period from randomisation to termination of trial Treatment • Disease control: across all assessment time-points during the period from randomisation to termination of trial Treatment • AEs:from date of signature of informed consent until 30 days after all Trial Treatment discontinuation • OS: time from the date of randomisation until death from any cause |
OR: en todos los puntos de tiempo de evaluación durante el período comprendido entre la asignación al azar y la terminación del ensayo. Tratamiento • Control de la enfermedad: en todos los puntos de tiempo de evaluación durante el período comprendido entre la asignación al azar y la terminación del ensayo. • AEs: a partir de la fecha de firma del consentimiento informado hasta 30 días después de la interrupción del tratamiento de todos los ensayos • OS: tiempo desde la fecha de la asignación al azar hasta la muerte por cualquier causa |
|
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | 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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Ireland |
Korea, Republic of |
Netherlands |
Singapore |
Switzerland |
|
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 required total trial follow-up duration is expected to be 48 months. Estimating a run-in period of 6 months, and a 6-month preparation of the report, the total trial duration is expected to be 5 years from enrolement of the first Patient. |
Se espera que la duración total requerida para el seguimiento del ensayo sea de 48 meses. La estimación de un período de ejecución de 6 meses, y una preparación de seis meses del informe, la duración total del ensayo se espera que sea de 5 años a partir del enrolamiento del primer paciente. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |