E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic Non-small cell lung cancer (NSCLC) |
CÁNCER DE PULMÓN NO MICROCÍTICO (CPNM) AVANZADO O METASTÁSICO |
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E.1.1.1 | Medical condition in easily understood language |
Advanced or metastatic NSCLC is lung cancer that has spread to areas near the lungs or other organs |
El CPNM avanzado o metastático es un cáncer de pulmón que se ha diseminado a áreas cercanas a los pulmones u otros órganos |
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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 | 20.0 |
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 | 20.0 |
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) |
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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 evaluate the efficacy of alectinib in patients with ALK/RET + advanced or metastatic NSCLC as determined by the blood somatic mutation profiling (bSMP) assay (Cohorts A and B) •To evaluate the efficacy of atezolizumab compared with platinum-based chemotherapy consisting of a platinum agent (cisplatin or carboplatin) in combination with either pemetrexed (non-squamous disease) or gemcitabine (squamous disease) in chemotherapy-naive patients with inoperable Stage IIIB or Stage IV NSCLC in patients who are biomarker positive by the blood tumor mutational burden (bTMB) assay (Cohort C) |
•Evaluar la eficacia de alectinib en pacientes con CPNM avanzado o metastásico RET+ determinado en el análisis bSMP (Cohortes A y B) • Evaluar la eficacia de atezolizumab comparado con quimioterapia basada en platino, que consiste en un compuesto derivado de platino (cisplatino o carboplatino) en combinación con pemetrexed (CPNM no escamoso) o gemcitabina (CPNM escamoso), en pacientes con CPNM inoperable en estadio IIIB o IV, no tratados previamente con quimioterapia, que son biomarcador positivo para bTMB (Cohorte C) |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the safety and tolerability of alectinib and atezolizumab (Cohorts A, B, and C) •To explore the pharmacokinetic (PK) characteristics of alectinib in RET+ patients (Cohort B) •To evaluate the impact of alectinib/ atezolizumab on patient-reported outcome (PROs) |
• Evaluar la seguridad y la tolerancia de alectinib y atezolizumab(Cohortes A, B y C) • Evaluar las características farmacocinéticas (PK) de alectinib en pacientes RET + (Cohorte B) • Evaluar el impacto de alectinib/atezolizumab sobre los PROs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC - Age >=18 years - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Measurable disease (as defined by RECIST, v1.1) - Adequate recovery from most recent systemic or local treatment for cancer - Adequate organ function - Life expectancy >=12 weeks - For female patients of childbearing potential and male patients, willingness to use acceptable methods of contraception |
• Presentar CPNM no resecable en estadio IIIb, no tratable con una modalidad de quimiorradiación combinada (avanzado) o en estadio IV (metastásico), con diagnóstico confirmado histológica o citológicamente • Tener 18 años de edad • Estado funcional del Eastern Cooperative Oncology Group (ECOG) 02 • Enfermedad medible (definida de acuerdo con los criterios RECIST,v1.1) • Se deben haber recuperado adecuadamente de los efectos del tratamiento sistémico o local más reciente para el cáncer • Función de órganos adecuada • Esperanza de vida 12 semanas • Las mujeres potencialmente fértiles y los varones deben estar dispuestos a utilizar métodos anticonceptivos aceptables |
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E.4 | Principal exclusion criteria |
- Inability to swallow oral medication - Women who are pregnant or lactating - Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments - History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, limited stage bladder cancer, Stage I uterine cancer, or other cancers from which the patient has been disease-free for at least 2 years -Significant cardiovascular disease -Known HIV positivity or AIDS-related illness -Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study -Inability to comply with other requirements of the protocol |
• Incapacidad para tomar medicamentos por vía oral • Mujeres embarazadas o en período de lactancia • Metástasis del SNC activas o no tratadas, evidenciadas en la evaluación con tomografía computarizada (TAC) o resonancia magnética (RM) realizada durante el período de selección y en estudios radiográficos previos • Antecedentes de otras neoplasias malignas en los 5 años previos a la selección en el estudio, exceptuando carcinoma in situ de cérvix, carcinoma de piel no melanoma, adenocarcinoma ductal in situ de mama, cáncer de próstata in situ, cáncer de vejiga en estadio limitado, cáncer de útero en estadio I, tratados adecuadamente, u otros tumores con un período libre de enfermedad durante al menos dos años • Enfermedad cardiovascular significativa • Positividad para VIH confirmada o patologías relacionadas con SIDA • Condiciones médicas concomitantes o antedentes de un trastorno previo que implique para el paciente un riesgo inaceptable en caso de que sea tratado con alguno de los fármacos del estudio o que afecten la interpretación de los datos del estudio • Incapacidad para cumplir los otros requisitos del protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Investigator-assessed ORR based on confirmed objective response (Cohorts A and B) 2. Investigator-assessed PFS according to RECIST v1.1 (Cohort C) |
1.IRO evaluada por el investigador basándose en la respuesta objetiva confirmada (cohortes A y B) 2. PSLP evaluado por el investigador de acuerdo con RECIST v1.1 (Cohorte C) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 6 years |
1-2. Hasta 6 años |
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E.5.2 | Secondary end point(s) |
1. Investigator-assessed DOR, CBR, and PFS per RECIST v1.1 (Cohorts A and B) 2. IRF-assessed ORR, DOR, CBR, and PFS per RECIST v1.1 (Cohorts A and B) 3. IRF-assessed PFS, ORR, and DOR according to RECIST v1.1 (Cohort C) 4. Investigator-assessed ORR, and DOR according to RECIST v1.1 (Cohort C) 5. OS (Cohorts A, B, and C) 6. Investigator-assessed PFS rates at 6-month and 1-year landmark timepoints (Cohort C) 7. Incidence, type, and severity of adverse events (based on the NCI CTCAE v4.0), including SAEs and AEs of special interest (Cohorts A, B, and C) 8. Changes in vital signs, physical findings, and clinical laboratory results during and following administration of protocol-specified IMPs (Cohorts A and B) 9. DLTs, if any, associated with alectinib at escalating doses in RET+ patients (Cohort B) 10. PK parameters of alectinib in RET+ patients (Cohort B) 11. Proportion of patients who improved compared with baseline in patient-reported lung cancer symptoms of cough, dyspnea, and chest pain and TTD as measured by SILC (Cohorts A, B, and C) 12. Mean change from baseline in HRQoL, patient functioning, and symptoms as measured by the EORTC QLQ-C30 (Cohorts A, B, and C) 13. Health status as assessed by the EQ-5D-5L questionnaire (Cohorts A, B, and C)) 14. Relationship between circulating biomarkers related to alectinib exposure and efficacy (Cohorts A and B) |
1. DR, IBC y SLP evaluados por el investigador de acuerdo con los criterios RECIST v1.1 (Cohortes A y B) 2. IRO, DR, IBC y SLP evaluados por un CRI de acuerdo con los criterios RECIST v1.1 (Cohortes A y B) 3. IRO, DR, IBC y SLP evaluados por un CRI de acuerdo con los criterios RECIST v1.1 (Cohorte C) 4. IRO, DR, IBC y SLP evaluados por un CRI de acuerdo con los criterios RECIST v1.1 (Cohorte C) 5. SG (Cohortes A, B, y C) 6. Tasas de SLP evaluadas por el investigador a 6 meses y 1 año, como puntos de referencia (Cohorte C) 7. Incidencia, tipo y severidad de los acontecimientos adversos (basándose en los criterios NCI CTCAE v4.0), incluyendo AAG y AA de especial interés (Cohortes A, B y C) 8. Cambios en las constantes vitales, hallazgos de la exploración física y resultados de las pruebas de laboratorio clínico durante y después de la administración de los MI especificados en el protocolo (Cohortes A y B) 9.TLD, si las hubiera, asociadas con las dosis ascendentes de alectinib en pacientes RET + (Cohorte B) 10. PK parámetros de alectinib en RET + pacientes (Cohorte B) 11. Proporción de pacientes que presentan mejoría respecto a la situación basal en los síntomas de cáncer de pulmón de tos, disnea y dolor torácico valorados por el paciente, basándose en la escala SILC (Cohortes A, B y C) 12 Variación media respecto a la situación basal en la CVRS, el nivel funcional del paciente y los síntomas, determinada basándose en el cuestionario EORTC QLQ-C30 y la escala SILC (Cohortes A, B y C) 13. Estado de salud valorado con el cuestionario EQ-5D-5L (Cohortes A,B y C) 14 Relación entre los biomarcadores circulantes asociados con la exposición y la eficacia de alectinib (Cohortes A y B) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to 6 years 6. At 6 month and 1 year 7-8. Up to 6 years 9. From Day 1 (D1) to D28 of Cycle 1 (C1) 10. Dose-Finding Phase: C1D1, C1D8, C2D1, C3D1, C4D1 Expansion Phase: C1D1, C2D1, C3D1, C4D1 11-14. Up to 6 years |
6. A los 6 meses y 1 año 7-8. Hasta 6 años 9. Desde el Día 1 (D1) hasta D28 del Ciclo 1 (C1) 10. Fase de búsqueda de dosis: C1D1, C1D8, C2D1, C3D1, C4D1 Fase de expansión: C1D1, C2D1, C3D1, C4D1 11-14. Hasta 6 años |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Australia |
Belgium |
Brazil |
Canada |
Chile |
France |
Germany |
Hong Kong |
Israel |
Italy |
Korea, Republic of |
Mexico |
Poland |
Spain |
Switzerland |
Thailand |
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 end of this study is defined as the date when the last patient, last visit (LPLV) or assessment occurs for the collection of the last data point for the last treatment cohort.
The umbrella nature of this protocol may provide for an extension of the overall duration of this study to meet the objectives of additional cohorts and/or additional therapies added through protocol amendments |
Este estudio terminará en la fecha en la que tenga lugar la última visita o evaluación del último paciente (UVUP) para la recogida de los últimos datos en la última cohorte de tratamiento. La estructura paraguas de este protocolo puede posibilitar que se prolongue la duración total de este estudio para cumplir los objetivos de las cohortes y/o los tratamientos adicionales que se añadan mediante enmiendas al protocolo |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |