E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and neck cancer of squamous cell origin |
cancer de células de origen escamoso de cuello y cabeza |
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E.1.1.1 | Medical condition in easily understood language |
Head and neck cancer of squamous cell origin |
cancer de células de origen escamoso de cuello y cabeza |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071537 |
E.1.2 | Term | Head and neck cancer stage III |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071536 |
E.1.2 | Term | Head and neck cancer stage IV |
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This is a phase II, open-label, randomized study of MEHD7945A versus cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck who have progressed during or following platinum-based chemotherapy. The main objective is to evaluate the efficacy of MEHD7945A (administered every 2 weeks) versus cetuximab (administered weekly) in all and in biomarker positive patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as measured by progression-free survival (PFS). |
Es un ensayo de fase II abierto, aleatorizado, sobre MEHD7945A frente a cetuximab en pacientes con CECCC R/M que han presentado progresión durante la quimioterapia con platino o después de ella. El objetivo principal es evaluar la eficacia de MEHD7945A (administrado cada 2 semanas) frente a cetuximab (administrado semanalmente) en todos los pacientes y en aquellos con biomarcador positivo con carcinoma recurrente o metastásico de células escamosas de cuello y cabeza, medido como supervivencia libre de progresión. |
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E.2.2 | Secondary objectives of the trial |
? To assess the clinical activity of MEHD7945A versus cetuximab, as measured by objective response rate, disease control rate, duration of objective response, time to disease progression, and overall survival in all patients and in biomarker positive patients ? To evaluate the safety and tolerability of MEHD7945A versus cetuximab ? To characterize the pharmacokinetics of MEHD7945A ? To evaluate the incidence and impact of anti-MEHD7945A antibodies |
-Evaluar la actividad clínica de MEHD7945A frente a cetuximab, medida por la tasa de respuesta libre de enfermedad, tasa de control de la enfermedad, duración de la respuesta libre de enfermedad, tiempo transcurrido hasta la progresión de la enfermedad y supervivencia global, en todos los pacientes y en pacientes cuyos tumores expresan concentraciones elevadas de HRG -Evaluar la seguridad y tolerabilidad de MEHD7945A frente a cetuximab. -Caracterizar la farmacocinética de MEHD7945A -Evaluar la incidencia y el efecto de los anticuerpos contra MEHD7945A |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
?Histologically confirmed Stage III or IV R/M SCCHN (according to the American Joint Committee on Cancer) that has progressed on or after platinum based chemotherapy and is not suitable for local therapy ?Progressive disease on or after a first-line platinum-based chemotherapy regimen for R/M SCCHN (maximum of six cycles) ?Availability and willingness to provide archival tumor tissue for biomarker testing ?Age ?18 years ?Male and female ?No healthy volunteers ?Life expectancy ?12 weeks ?ECOG 0-2 ?Disease that is measurable per RECIST v1.1 ?Adequate hematologic and end-organ function |
-CECCC R/M en estadios III o IV confirmados histológicamente (de acuerdo con el Comité Conjunto estadounidense sobre Cáncer) que ha progresado durante o después de quimioterapia con platino y no apto para tratamiento local -Consentimiento para proporcionar tejido tumoral de archivo para el estudio de biomarcadores -Progresión de la enfermedad durante o después de una quimioterapia de primera línea con platino para un CECCC R/M (máximo de seis ciclos) -Edad ? 18 años -Hombres y mujeres -No voluntaries sanos -Esperanza de vida igual o superior a 12 semanas -Estado funcional según ECOG de 0-2 -Enfermedad mensurable conforme a los criterios RECIST v1.1 -Función hematológica y de los posibles órganos afectados adecuada, |
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E.4 | Principal exclusion criteria |
?Nasopharyngeal cancer ?Prior treatment with an investigational or approved agent for the purpose of inhibiting HER family members with the exception of treatment with an EGFR inhibitor as part of definitive therapy for locally advanced disease and if completed/terminated within more than one year before study enrollment ?Last anti tumor therapy within 4 weeks prior to Day 1 of the study treatment ?Major surgical procedure within 4 weeks prior to Day 1 of the study treatment ?Current severe, uncontrolled systemic disease ?History of cardiac heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment ?History of myocardial infarction within 6 months prior to Day 1 of the study treatment, or history of unstable angina ?Clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; or current alcohol abuse ?Clinically significant gastrointestinal bleeding within 6 months prior to Day 1 of the study treatment ?History of ILD ?History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy ?Primary central nervous system (CNS) malignancy or untreated/active CNS metastases ?Women during pregnancy or lactation |
-Cáncer nasofaríngeo -Tratamiento anterior con un fármaco en investigación o aprobado para inhibir los miembros de la familia HER con la excepción de tratamiento con un inhibidor del EGFR en el marco de un tratamiento definitivo para enfermedad localmente avanzada y se completó o terminó al menos 1 año antes de la inclusión en el estudio. -Último tratamiento antitumoral en las 4 semanas anteriores al día 1 -Intervención de cirugía mayor en las 4 semanas anteriores al día 1 del ciclo 1. -Enfermedad sistémica actual grave no controlada -Antecedentes de insuficiencia cardíaca de cualquier grado según la New York Heart Association o arritmia cardíaca grave que precise tratamiento -Antecedentes de infarto de miocardio en los 6 meses anteriores al día 1 del ciclo 1 o antecedentes de angina de pecho inestable. -Hepatopatía conocida clínicamente importante, como hepatitis activa viral, alcohólica o de otro tipo, cirrosis o alcoholismo actual -Hemorragia digestiva de trascendencia clínica en los 6 meses anteriores al día 1 del ciclo 1 -Historia de enfermedad pulmonar intersticial -Antecedentes de reacción alérgica o hipersensibilidad intensa (de grados 3 o 4) a anticuerpos terapéuticos que haya requerido la interrupción del tratamiento. -Neoplasia maligna primaria del sistema nervioso central (SNC) o metástasis del SNC no tratadas o activas -Embarazo (prueba de embarazo positiva) o lactancia |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is PFS. PFS is defined as the time from randomization to documented disease progression assessed by the investigator or death on study, whichever occurs first. |
La variable primaria es la supervivencia libre de progresión, definida como el tiempo transcurrido desde la aleatorización hasta la progresión documentada de la enfermedad según la evaluación del investigador o la muerte durante el estudio, lo que ocurra antes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Data for each patient without documented disease progression or death on study will be censored at the time of his or her last tumor assessment. If no tumor assessments were performed after the baseline visit, the data will be censored at the time of randomization plus 1 day. Death on study is defined as death from any cause within 30 days of the last dose of study treatment. |
Los datos de los pacientes sin progresión documentada de la enfermedad ni muerte durante el estudio se censurarán en el momento de su última evaluación tumoral. Si después de la visita inicial no se realizaron evaluaciones tumorales, los datos se censurarán en el momento de la aleatorización más 1 día. La muerte en el estudio se define como la muerte debida a cualquier causa dentro de los 30 días tras la última dosis del tratamiento en estudio. |
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E.5.2 | Secondary end point(s) |
?Objective response, disease control, duration of objective response, time to disease progression, and overall survival ?Incidence, nature, and severity of adverse events, graded according to the NCI CTCAE v4.0 ?Clinically significant changes in vital signs, physical findings, and clinical laboratory results during and following administration of study treatment ?MEHD7945A minimum and maximum serum concentration prior to infusion on Day 1 of Cycles 1 through 4 and at study completion (only Cmin at study completion) ?Serum anti-therapy antibodies (ATAs) to MEHD7945A prior to infusion on Day 1 of Cycles 1 and 4 and at study completion |
Respuesta objetiva, control de la enfermedad, duración de la respuesta objetiva, tiempo transcurrido hasta la progresión de la enfermedad, y supervivencia global. -Incidencia, naturaleza y acontecimientos adversos graves, con arreglo al grado de los CTCAE del INC (versión 4.0) -Cambios clínicamente significativos en las constantes vitales, hallazgos físicos, y resultados clínicos de laboratorio durante y tras la administración del tratamiento en estudio. -Concentración sérica mínima y máxima de MEHD7945A antes de la infusión el día 1 de los ciclos 1 a 4 y al final del estudio -Anticuerpos frente a MEHD7945A (ATAs) séricos frente a MEHD7945A antes de la infusión el día 1 de los ciclos 1 y 4, y al final del estudio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Objective response is defined as a complete or partial response according to RECIST v1.1; objective responses must be confirmed ?4 weeks after the initial response. - for other timepoints: as stated above in E.5.2 |
La respuesta libre de enfermedad se define como una respuesta completa o parcial conforme a los criterios RECIST v.1.1; las respuestas objetivas deben confirmarse al menos 4 semanas después de determinar la respuesta inicial. -para otras variables: fijadas en E.5.2 |
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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 | Yes |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Bulgaria |
France |
Germany |
Hungary |
Italy |
Romania |
Spain |
United Kingdom |
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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Study closure is expected to occur either 12 months after the last patient is enrolled in the study or when all patients in the study have died, whichever occurs first. |
el cierre del estudio se espera que ocurra o bien 12 meses tras la inclusión del último paciente del estudio o bien cuando todos los pacientes del estudio hayan fallecido, lo que ocurra primero. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |