| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| ALK-mutated Non-small cell lung cancer |
| cancer de pulmón no microcítico con mutación ALK |
|
| E.1.1.1 | Medical condition in easily understood language |
| ALK-mutated Non-small cell lung cancer |
| cancer de pulmón no microcítico con mutación ALK |
|
| 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 | 14.1 |
| 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 |
The primary objectives for Part 1 of the study are as follows:
To determine the recommended Phase II dose (RP2D) of RO5424802 to be used in Part 2 of the study
? To evaluate the safety and tolerability of 600-mg and 900-mg (if 900 mg is reached) doses of RO5424802 administered twice-daily for 21 days to patients with locally advanced or metastatic NSCLC (stage IIIb or stage IV) who have anaplastic lymphoma kinase (ALK) re-arrangement and in whom prior crizotinib therapy has failed
? To characterize the pharmacokinetics (PK) of RO5424802
The primary efficacy objectives for Part 2 study are as follows:
?To evaluate efficacy of RO5424802 by objective response rate (ORR) as per central independent radiological review committee (IRC) using RECIST criteria version 1.1 in the overall population [with and without prior exposure of cytotoxic chemotherapy treatment(s)]. |
Los objetivos principales de la parte 1 de este estudio son:
? Determinar la dosis de RO5424802 recomendada para la fase II (DRF2) que se utilizará en la parte 2 del estudio
? Evaluar la seguridad y la tolerabilidad de las dosis de 600 y 900 mg (si se alcanza la de
900 mg) de RO5424802 administrado dos veces al día durante 21 días a pacientes con CPNM localmente avanzado o metastásico (en estadio IIIb o IV) que presenten reordenación de la cinasa del linfoma anaplásico (ALK) y en quienes haya fracasado el tratamiento previo con crizotinib
? Describir la farmacocinética (FC) de RO5424802
Los objetivos de eficacia principales de este estudio son los siguientes:
Evaluar la eficacia de RO5424802 mediante la tasa de respuestas objetivas (TRO), determinada por el comité de revisión radiológica independiente (CRI) central con la versión 1.1 de los criterios RECIST en la población global de pacientes [con y sin exposición previa a uno o varios tratamientos de quimioterapia citotóxica] |
|
| E.2.2 | Secondary objectives of the trial |
?To evaluate efficacy of RO5424802 by objective response rate (ORR) as
per central IRC using RECIST criteria version 1.1 in patients without
prior exposure of cytotoxic chemotherapy treatment(s)
?To evaluate efficacy of RO5424802 by ORR per investigator review of
radiographs using RECIST 1.1
?To evaluate disease control rate (DCR) of RO5424802 based on IRC and
investigator review of radiographs |
Evaluar la eficacia de RO5424802 mediante la tasa de respuestas objetivas (TRO),
determinada por el comité de revisión radiológica independiente (CRI) central con la
versión 1.1 de los criterios RECIST en la población global de pacientes [con y sin
exposición previa a uno o varios tratamientos de quimioterapia citotóxica]
? Evaluar la eficacia de RO5424802 mediante la tasa de respuestas objetivas (TRO),
determinada por el CRI central con la versión 1.1 de los criterios RECIST en pacientes
con exposición previa a uno o varios tratamientos de quimioterapia citotóxica |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Patients with locally advanced or metastatic NSCLC (stage IIIB or stage IV by AJCC 7th)
2.Male or female ?18 years old
3.Life expectancy, in the opinion of the investigator, of at least 12 weeks
4.ECOG Performance Status of 0?2
5.Histologically confirmed NSCLC
6.Documented ALK rearrangement based on an FDA approved test
7.Prior treatment with crizotinib and progression based on RECIST criteria version 1.1 with the last dose of crizotinib being within 60 days from enrolment. Patients can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy |
?Pacientes con CPNM localmente avanzado o metastásico (estadio IIIB o IV según la 7ª edición del manual del AJCC)
?Varón o mujer de edad _ 18 años
?Esperanza de vida de al menos 12 semanas en opinión del investigador
?Estado funcional del ECOG de 0-2
?CPNM confirmado mediante histología
?Reordenación de ALK documentada según una prueba aprobada por la FDA
?Tratamiento previo con crizotinib y progresión según la versión 1.1 de los criterios RECIST, con la última dosis de crizotinib administrada en los 60 días previos al reclutamiento. Los pacientes podrán no haber recibido ningún tratamiento anterior de quimioterapia o haber recibido al menos un régimen previo de quimioterapia basado en platino |
|
| E.4 | Principal exclusion criteria |
1.Receipt of any other ALK inhibitors in addition to crizotinib
2.Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks prior to Day 1. Patients who received crizotinib or other tyrosine kinase inhibitors need to have a minimum 2-week wash-out period before the first dose
3.A previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal cancer by endoscopic resection, in situ carcinoma of the cervix or any cured cancer that is considered to have no impact on PFS and OS for the current NSCLC)
4.Active or uncontrolled infectious diseases requiring treatment
5.NCI CTCAE (version 4.03) Grade 3 or higher toxicities due to prior therapy that has not shown improvement and are considered to interfere with current study medication.
6.History of organ transplant
7.Co-administration of anti-cancer therapies other than those administered in this study. |
?Tratamiento con otros inhibidores de ALK además de crizotinib
?Tratamiento con cualquier quimioterapia citotóxica previa para el CPNM con ALK positiva en las 4 semanas previas al día 1. Los pacientes que hayan recibido crizotinib u otros inhibidores de la tirosina cinasa tendrán que pasar por un período de lavado mínimo de 2 semanas antes de la primera dosis
?Neoplasia maligna previa en los últimos 3 años (excepto carcinoma basocelular de la piel tratado de forma curativa, cáncer digestivo precoz tratado mediante resección endoscópica, carcinoma del cuello uterino in situ o cualquier cáncer curado que se considere que no tiene ningún efecto sobre la SSP o la SG para el CPNM actual)
?A previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal cancer by endoscopic resection, in situ carcinoma of the cervix or any cured cancer that is considered to have no impact on PFS and OS for the current NSCLC)
?Enfermedades infecciosas activas o no controladas con necesidad de tratamiento
?Toxicidad de grado 3 o superior de los NCI-CTCAE (versión 4.03) debida al tratamiento previo, que no haya mostrado mejoría y se considere que interfiere con la medicación actual del estudio
?Antecedentes de trasplante de órganos
?Administración conjunta de tratamientos antineoplásicos distintos de los fármacos del estudio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1 ? Determination of a Phase II recommended dose ? Dose Escalation Study
?Incidence of DLTs by NCI CTCAE v4.03 grade and associated dose of RO5424802 (600 and 900 mg BID)
Part 2 ? Evaluation of Safety and Efficacy of RO5424802 in ALK-positive NSCLC Patients with ALK Rearrangements.
?Objective tumor response rate (PR and CR) as assessed by an independent radiological review committee using RECIST v1.1
?Objective responses must be confirmed ?28 days after initial response; [Primary in the ?all patients? and ?patients who have received at least one line of platinum-based cytotoxic chemotherapy? groups |
Parte 1- determinación de una dosis recomendada en fase II ? Estudio de escalada de dosis
Incidencia de TLDs en base al NCI CTCAE v4.03 y asociado a la dosis de RO5424802 (600 y 900 mg dos veces al día
Part 2 ? Evaluación de la seguridad y eficacia de RO5424802 en pacientes con CPNM ALK-positive con reordenamientos ALK.
Grado de respuesta tumoral (RP y RC) valorado por un comité de revisión radiológica independiente usando RECIST v1.1
Las respuestas deben confirmarse ?28 días tras la respuesta inicial ; [primaria en los grupos de ?todos los pacientes ? y ?pacientes que han recibido al menos una línea de quimioterapia citotóxica basada en platinos? . |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Please refer to E.5.1 |
| Ver E.5.1 |
|
| E.5.2 | Secondary end point(s) |
? To evaluate efficacy of RO5424802 by ORR per investigator review of radiographs using RECIST 1.1
? To evaluate disease control rate (DCR) of RO5424802 based on IRC and investigator review of radiographs
? To assess duration of response (DOR) in patients treated with RO5424802 based on IRC and investigator review of radiographs |
? evaluar la eficacia de RO5424802 por ORR según evisión de radiografías por el investigador usando RECIST 1.1
? evaluar el grado de control de la enfermedad (DCR) de RO5424802 en base a IRC y revisión por el invesigador de radiografías.
? valorar la duración de respuesta (DOR) en pacientes tratados con RO5424802 en base al IRC y a la revisión de radiografías por el investigator |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to E.5.2 |
| Ver E.5.2 |
|
| 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 | No |
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Dose escalation |
| Escalada de dosis |
|
| 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 | 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Russian Federation |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
| The end of the study is defined as the date when the last patient, last visit (LPLV) occurs. As patients will be offered continued treatment beyond progression with RO5424802 alone or in combination with erlotinib depending on their EGFR status and whether the treating physicians consider that the patient is still benefiting from RO5424802 treatment, LPLV is expected to occur when the last patient has either died or is lost to follow-up. |
| Se define como Ultima visita del ultimo paciente. Como a los pacientes se les ofrecerá continuar con el tratamiento tras la progresión con RO5424802 solo o en combinación con erlotinib dependiendo de la situación EGFR y si los médicos consideran que el paciente está todavía beneficiándose del tratamiento RO5424802, UVUP se espera ocurra cuando el ultimo paciente haya fallecido o se haya perdido su seguimiento. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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