E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Squamous Cell (Sq) Non-Small Cell Lung Cancer (NSCLC) |
Cáncer de pulmón no microcítico (CPNM) epidermoide avanzado o metastásico |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 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 determine the incidence of high-grade (CTCAE v4.0 Grades 3-4), treatment-related, select adverse events in subjects with advanced or metastatic SqNSCLC who progressed during or after at least 2 systemic therapies. |
Determinar la incidencia de determinados acontecimientos adversos relacionados con el tratamiento de alto grado (grados 3-4 según los CTCAE, versión 4.0) en sujetos con CPNM epidermoide avanzado o metastásico que han presentado progresión durante o después de recibir al menos dos líneas de tratamiento sistémico previas. |
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E.2.2 | Secondary objectives of the trial |
-To determine the incidence and to characterize the outcome of all high-grade (CTCAE v4.0 Grades 3-4), select adverse events in subjects with advanced or metastatic SqNSCLC who have progressed during or after at least 2 prior systemic therapies and are treated with nivolumab monotherapy -To estimate overall survival (OS) in all treated subjects -To estimate investigator-assessed objective response rate (ORR) |
-Determinar la incidencia y definir el desenlace de determinados acontecimientos adversos de alto grado (grados 3-4 según los CTCAE, versión 4.0) en sujetos con CPNM epidermoide avanzado o metastásico que han presentado progresión durante o después de recibir al menos dos líneas de tratamiento sistémico previas y que sean tratados con nivolumab en monoterapia. -Calcular la supervivencia global (SG) en todos los sujetos tratados. -Calcular la tasa de respuestas objetivas (TRO) conforme a la evaluación del investigador |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria a) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): i) PS 0 to 1 (Subgroup1) ii) PS 2 (Subgroup 2; maximum of 300 subjects; clinical risk/benefit ratio will be monitored by the Scientific Steering Committee following a Safety Management Plan b) Subjects with histologically or cytologically-documented SqNSCLC who presented with stage IIIb/stage IV disease or who developed recurrent or progressive disease following prior definitive therapy for localized or local advanced disease. Enrollees must not be eligible for another clinical study with nivolumab. A fresh biopsy is not required to take part in the study. c) Subjects must have experienced disease progression or recurrence during or after both a platinum doublet-based chemotherapy regimen and at least 1 additional systemic therapy i) Additional systemic therapies are defined as agents that are locally accepted and established for use as monotherapy or in combination for the treatment of stage IIIb/stage IV SqNSCLC. ii) Experimental therapies when given as a separate regimen are considered as separate lines of therapy. iii) Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate line of therapy. iv) Prior platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease is considered first-line therapy only if recurrent (local or metastatic) or progressive disease developed within 6 months of completing therapy. Subjects with recurrent disease > 6 months must also have progressed during or after at least 2 subsequent regimens (a platinum doublet-based chemotherapy regimen and at least 1 additional systemic therapy OR at least 2 additional systemic therapies) given to treat the recurrence d) Subjects with CNS metastases: i) Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first dose. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of < or = 10 mg daily prednisone (or equivalent) OR ii) Subjects are eligible if they have previously untreated CNS metastases that are neurologically asymptomatic. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of < or = 10 mg daily prednisone (or equivalent) |
Criterios de inclusión fundamentales a) Estado funcional (EF) del Eastern Cooperative Oncology Group (ECOG): i) EF de 0 a 1 (subgrupo 1) ii)EF de 2 (subgrupo 2; máximo de 300 sujetos; el comité de dirección científica evaluará la relación beneficio/riesgo clínico conforme a un plan de gestión de la seguridad. b) Sujetos con CPNM epidermoide confirmado mediante histología o citología que hayan debutado con enfermedad en estadio IIIb/IV o que hayan presentado recidiva o progresión de la enfermedad después de un tratamiento definitivo previo por enfermedad localizada o avanzada local. Los sujetos incluidos no podrán ser elegibles para participar en otro estudio clínico de nivolumab. No se exigirá una biopsia reciente para participar en el estudio. c) Los sujetos tendrán que haber presentado progresión de la enfermedad o recidiva durante o después de recibir una pauta de quimioterapia con dos fármacos a base de platino y al menos un tratamiento sistémico adicional. i) Se entiende por tratamiento sistémico adicional todo medicamento que se encuentre aceptado localmente y esté aceptado para uso en monoterapia o en combinación para el tratamiento del CPNM epidermoide en estadio IIIb/IV. ii) Los tratamientos experimentales, cuando se administren como regímenes independientes, se considerarán líneas independientes de tratamiento. iii) El tratamiento de mantenimiento tras la quimioterapia con dos fármacos a base de platino no se considerará una línea independiente de tratamiento. iv) La quimiorradioterapia adyuvante, neoadyuvante o definitiva con platino previa, administrada por enfermedad localmente avanzada, solo se considerará tratamiento de primera línea en caso de que se haya producido recidiva (local o metastásica) o progresión de la enfermedad en los seis meses siguientes a la finalización del tratamiento. Los sujetos con recidiva de la enfermedad más de seis meses después de que haya finalizado el tratamiento previo también tendrán que haber presentado progresión durante o después de recibir al menos dos líneas de tratamiento posteriores (una pauta de quimioterapia con dos fármacos a base de platino y al menos un tratamiento sistémico adicional O al menos dos tratamientos sistémicos adicionales) administradas para tratar la recidiva. d) Sujetos con metástasis en el SNC: i) Estos sujetos podrán participar si se tratan las metástasis en el SNC y recuperan el estado neurológico basal (salvo los signos o síntomas residuales relacionados con el tratamiento del SNC) durante al menos dos semanas antes de la primera dosis. Además, no podrán estar recibiendo corticoides o bien tendrán que estar recibiendo una dosis estable o decreciente < o = 10 mg de prednisona al día (o equivalente). O ii) Estos sujetos podrán participar si presentan metástasis en el SNC no tratadas previamente y asintomáticas desde el punto de vista neurológico. Además, no podrán estar recibiendo corticoides o bien tendrán que estar recibiendo una dosis estable o decreciente < o = 10 mg de prednisona al día (o equivalente). |
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E.4 | Principal exclusion criteria |
Key exclusion criteria: a) Subjects with untreated, symptomatic CNS metastases are excluded b) Subjects with carcinomatous meningitis are excluded. |
Criterios de exclusión fundamentales a) Sujetos con metástasis en el SNC sintomáticas y no tratadas. b) Sujetos con meningitis carcinomatosa |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of high-grade (CTCAE v4.0 Grades 3-4 or higher), treatment-related, select adverse events |
El criterio de valoración principal es la incidencia de determinados acontecimientos adversos relacionados con el tratamiento de alto grado (grados 3-4 según los CTCAE, versión 4.0). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints include: -Incidence of high grade (Grade 3-4) select adverse events -Median time to onset and median time to resolution (Grades 3-4) of select adverse events -OS is defined as the time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive. OS will be followed continuously while subjects are on treatment and every 3 months via in-person or phone contact after subjects discontinue the study drug. -ORR is defined as the number and percentage of subjects with a best overall response (BOR) of confirmed CR or PR. ORR as assessed by the investigator will be reported. |
Los criterios de valoración secundarios comprenden: -Incidencia de determinados acontecimientos adversos de alto grado (grados 3-4). -Mediana del tiempo transcurrido hasta la aparición y mediana del tiempo transcurrido hasta la resolución de determinados acontecimientos adversos (grados 3-4). -SG definida como el tiempo transcurrido entre la fecha de la primera administración y la fecha de la muerte. Los datos de los sujetos que no hayan fallecido serán objeto de censura estadística en la última fecha en que se sepa que seguían vivos. Se hará un seguimiento continuo de la SG mientras los sujetos reciban el fármaco del estudio y cada tres meses, mediante contacto en persona o por teléfono, después de que suspendan el tratamiento. -TRO definida como el número y el porcentaje de sujetos con una mejor respuesta global (MRG) de RC o RP confirmada. Se comunicará la TRO conforme a la evaluación del investigador. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life data |
Datos de calidad de vida |
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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) | 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 | 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.8.3 |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 195 |
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 |
Austria |
Belgium |
Bulgaria |
Croatia |
Czech Republic |
Denmark |
Finland |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Lithuania |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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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LVLS |
última visita último sujeto |
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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 | 5 |
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 | 5 |
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 |