E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent and/or metastatic head and neck squamous cell carcinoma in patients who have progessed after platinum based therapy |
Carcinoma de células escamosas de cabeza y cuello recurrente y/o metastásico en pacientes que han progresado tras recibir terapia con platino. |
|
E.1.1.1 | Medical condition in easily understood language |
Head and neck cancer |
Cáncer de cabeza y cuello |
|
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 | 14.0 |
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) |
|
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 investigate the efficacy of afatinib versus methotrexate therapy in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who have progressed after platinum-based therapy given for R/M HNSCC |
Investigar la eficacia de afatinib frente al tratamiento con metotrexato en pacientes con carcinoma de celulas escamosas de cabeza y cuello (HNSCC) recurrente y/o metastásico que hayan mostrado progresión tras terapia con platino administrada para HNSCC recurrente o metastásico. |
|
E.2.2 | Secondary objectives of the trial |
To investigate the safety of afatinib versus methotrexate therapy in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who have progressed after platinum-based therapy given for R/M HNSCC |
Investigar la seguridad de afatinib frente al tratamiento con metotrexato en pacientes con carcinoma de celulas escamosas de cabeza y cuello (HNSCC) recurrente y/o metastásico que hayan mostrado progresión tras terapia con platino administrada para HNSCC Rerurrente o metastásico. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Incl crit #1: Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, which has recurred/metastasised and is not amenable for salvage surgery or radiotherapy. Incl crit #2: Documented progressive disease based on investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST) following receipt of cisplatin and/or carboplatin (minimum doses described below) administered for recurrent and/or metastatic disease independent of whether patient progressed during or after platinum based therapy. Cisplatin, minimum dose: at least two cycles of cisplatin, 60 mg/m2/cycle or a total cumulative dose of 120 mg/m2 during 8 weeks Carboplatin, minimum dose: at least two cycles of carboplatin area under the concentration-time curve (AUC) 4/cyclecycle or a total cumulative dose of AUC 8 during eight weeks. Incl crit #3: Measurable disease according to RECIST (version 1.1). Incl crit #4: ECOG performance status 0 or 1 at the time of randomisation |
- Carcinoma de células escamosas, confirmado por histología o citología, de la cavidad oral, orofaringe, hipofaringe o laringe, que haya recurrido/metastatizado y no sea susceptible de cirugía o radioterapia de rescate.
-Enfermedad progresiva documentada según evaluación del investigador de acuerdo con los Criterios de Evaluación de Respuesta en Tumores Sólidos (RECIST) tras recibir cisplatino y/o carboplatino (dosis mínimas descritas más abajo) administrados para enfermedad recurrente y/o metastásica independientemente de si la enfermedad progresó durante o después de la terapia basada en platino.
- Cisplatino, dosis mínima: al menos dos ciclos de cisplatino, ?60 mg/m2/ciclo o una dosis total acumulada de ?120 mg/m2 durante ocho semanas
- Carboplatino, dosis mínima: al menos dos ciclos de carboplatino con área bajo la curva concentración-tiempo (AUC) ?4/ciclo o una dosis total acumulada de AUC ?8 durante ocho semanas.
- Enfermedad medible según RECIST (versión 1.1).
- Estado general según ECOG de 0 o 1 en el momento de la aleatorización. |
|
E.4 | Principal exclusion criteria |
Excl crit #1: Progressive disease within three months of completion of curatively intended treatment for locoregionally advanced or for metastatic HNSCC. Excl crit #3: More than one chemotherapeutic regimen given for recurrent and/or metastatic disease. Excl crit #4: Prior treatment with EGFR-targeted small molecules. Excl crit #5: Unresolved chronic toxicity, other than hearing loss, tinnitus or dry mouth, CTCAE grade >2 from previous anti-cancer therapy or unresolved skin toxicities CTCAE grade >1 and/or diarrhoea CTCAE grade >1 caused by prior treatment with EGFR targeted antibodies. |
-Enfermedad progresiva en los tres meses posteriores a la finalización de un
tratamiento planeado como curativo para HNSCC locorregionalmente avanzado o
metastásico.
- Más de un régimen de quimioterapia administrado para enfermedad recurrente
y/o metastásica.
- Tratamiento previo con moléculas pequeñas dirigidas frente a EGFR.
- Toxicidad crónica no resuelta, distinta de pérdida auditiva, tinnitus o sequedad de
boca de grado >2 CTCAE por terapia antineoplásica previa o toxicidades
cutáneas no resueltas de grado >1 CTCAE y/o diarrea de grado >1 CTCAE
originadas por tratamiento previo con anticuerpos dirigidos frente a EGFR. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) |
supervivencia sin progresión (SSP) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 364 disease progression events, estimated to be approximately 20 months after start of recruitment. |
Tras 364 acontecimientos de progresión, que se estima que ocurrirán tras 20 meses del inicio del reclutamiento, aproximadamente. |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoint is Overall Survival (OS). Other secondary enpoints are Objective Response and Health related quality of life (HRQOL). |
Criterio secundario de valoración clave es Supervivencia global (SG). Otros criterios secundarios de evaluación son
- Respuesta objetiva basada en RECIST versión 1.1
- Calidad de vida relacionada con la salud (HRQOL) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 343 death events, estimated to be approximately 26 months after start of recruitment. For the key secondary endpoint OS a futility analysis will be made after approximately 40% of the death events, estimated to be after 14 months after start of recuitment. |
Tras 343 fallecimientos, que se estima que ocurran tras 26 meses del inicio del reclutamiento, aproximadamente. Para el criterio secundario de valoración SG se realizará un análisis intermedio de utilidad cuando se hayan producido alrededor del 40% de las muertes, que se estima que ocurra tras 14 meses del inicio del reclutamiento. |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
Argentina |
Austria |
Belgium |
Brazil |
Chile |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Mexico |
Netherlands |
Peru |
Russian Federation |
South Africa |
Spain |
Sweden |
Switzerland |
United States |
|
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 trial is considered completed after all patients have progressed and the required number of death events has occurred |
|
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |