E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Loco-regionally advanced head and head squamous cell carcinoma with no evidence of disease after chemo-radiotherapy |
Carcinoma de células escamosas de cabeza y cuello locorregionalmente avanzado sin evidencia de enfermedad tras quimiterapia. |
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E.1.1.1 | Medical condition in easily understood language |
Head and neck cancer |
Cáncer de cabeza y cuello |
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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 | 14.0 |
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) |
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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 investigate the efficacy of afatinib over placebo when given as adjuvant therapy after chemo-radiotherapy (CRT) in primary unresected patients with loco-regionally advanced squamous cell carcinoma stage III or IVa/b of the oral cavity, oropharynx, or hypopharynx, or larynx stage IVa/b |
Investigar la eficacia de afatinib sobre placebo cuando se administra como terapia adyuvante tras quimio-radioterapia (QRT) en pacientes no sometidos a resección primaria con carcinoma de células escamosas locorregionalmente avanzado en estadio III o IVa/b de la cavidad oral, orofaringe o hipofaringe o estadio IVa/b de laringe. |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety of afatinib over placebo when given as adjuvant therapy after chemo-radiotherapy (CRT) in primary unresected patients with loco-regionally advanced squamous cell carcinoma stage III or IVa/b of the oral cavity, oropharynx, or hypopharynx, or larynx stage IVa/b |
Investigar la la seguridad de afatinib sobre placebo cuando se administra como terapia adyuvante tras quimio-radioterapia (QRT) en pacientes no sometidos a resección primaria con carcinoma de células escamosas locorregionalmente avanzado en estadio III o IVa/b de la cavidad oral, orofaringe o hipofaringe o estadio IVa/b de laringe. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
?Histologically or cytologically confirmed loco-regionally advanced squamous cell carcinoma, stage III, IVa, or IVb, of the oral cavity, oropharynx, or hypopharynx, or larynx stage IVa or IVb ?Unresected tumour prior to chemo-radiotherapy due to: o Technical unresectability (tumour fixation/invasion to either base of the skull, cervical vertebrae, nasopharynx, or fixed lymph nodes); and/or o Low surgical curability (T3-T4, N2-N3 excluding T1N2); and/or o Organ preservation ?Concomitant platinum-based chemo-radiotherapy (for minimum requirements see the protocol) completed no longer than 16 weeks prior to randomisation. At randomisation, chemo-radiotherapy induced side effects CTCAE grade ? 2 ?Within 16 weeks after concomitant platinum-based CRT, no evidence of disease (NED), defined as no residual tumour, i.e. no measurable or palpable tumour on clinical and radiographic (e.g. CT scan or MRI) examinations as judged by the investigator. In case of palpable mass, NED must be confirmed by biopsy ?ECOG performance status 0 or 1 at the time of randomisation |
1. Carcinoma de células escamosas locorregionalmente avanzado confirmado mediante histología o citología. a) estadios III, IVa o IVb, de la cavidad oral, orofaringe o hipofaringe, o b) laringe estadio IVa o IVb 2. Tumor no sometido a resección antes de la quimio-radioterapia debido a: a) Incapacidad técnica para resección (fijación / invasión tumoral en la base del cráneo, las vértebras cervicales, nasofaringe o nódulos linfáticos fijados) y/o b) Baja curación quirúrgica (T3-T4, N2-N3 excluyendo T1N2) y/o c) Conservación de órgano 3. Quimio-radioterapia concomitante basada en platino finalizada no más de 16 semanas antes de la asignación aleatoria (randomización): a) En la asignación aleatoria, efectos secundarios inducidos por la quimio-radioterapia grado CTCAE 2 (excepción: los pacientes con sonda de alimentación son elegibles si el paciente se ha recuperado del acontecimiento adverso que requería sonda de alimentación) 4. Ausencia de evidencia de enfermedad en las 16 semanas posteriores a la QRT concomitante basada en platino, definida como ausencia de tumor residual, es decir, sin tumor medible o palpable en los exámenes clínicos o radiográficos (p. ej. TAC o RMN) según criterio del investigador. En caso de masa palpable, la ausencia de evidencia de enfermedad debe confirmarse mediante biopsia |
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E.4 | Principal exclusion criteria |
?Patients with smoking history of ? 10 pack years and with primary tumour site base of tongue ?Patients with smoking history of ? 10 pack years and with primary tumour site tonsil ?Primary cancer of nasopharynx, sinuses, or salivary glands ?Prior treatment with EGFR-targeted small molecules, EGFR-targeted antibodies, and/or any investigational agents for treatment of HNSCC |
Pacientes con hábitos de tabaquismo de 10 paquetes de tabaco por año y con tumor primario situado en la base de la lengua Pacientes con hábitos de tabaquismo de 10 paquetes de tabaco por año y con tumor primario situado en la amígdala Cáncer primario de nasofaringe, senos y/o glándulas salivares Tratamiento previo con moléculas pequeñas inhibidoras del EGFR, anticuerpos inhibidores de EGFR y/o cualquier agente en investigación para el tratamiento de HNSCC |
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E.5 End points |
E.5.1 | Primary end point(s) |
Disease Free Survival (DFS) |
Supervivencia libre de enfermedad (SLE) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 4 years |
Aproximadamente 4 años |
|
E.5.2 | Secondary end point(s) |
DFS rate at 2 years Overall Survival (OS) Health Related Quality of Life (HRQOL) |
Tasa de supervivencia libre de enfermedad a los 2 años Supervivencia global (SG) Calidad de vida relacionada con la salud (HRQOL) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 4 years |
Aproximadamente 4 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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | No |
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 | 68 |
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 |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
Denmark |
Finland |
France |
Germany |
Greece |
Ireland |
Italy |
Japan |
Mexico |
Netherlands |
Peru |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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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 will be completed two years after the last patient is randomised and at least 408 events (tumour recurrences or deaths) have occurred, whichever comes last. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |