| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have not received prior systemic chemotherapy. |
| Pacientes con CCECC recurrente o metastásico que no hayan recibido quimioterapia sistémica previa por CCECC recurrente o metastásico. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Specific type of cancer of head and neck called "squamous cell carcinoma of the head and neck" (SCCHN) |
| Tipo de cáncer específico de cabeza y cuello "Carcinoma de células escamosas de cabeza y cuello" (CCECC) |
|
| 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 | 18.1 |
| 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) |
|
| 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 assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS and OS |
| Evaluar la eficacia del tratamiento de combinación de MEDI4736 + tremelimumab en comparación con el TdR en términos de SLP y SG |
|
| E.2.2 | Secondary objectives of the trial |
To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS, ORR, DoR, APF12, PFS2, OS, and OS24
To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS, ORR, PFS2, OS, and OS24
To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS, ORR, and OS
To assess disease-related symptoms and health-related quality of life in patients treated with MEDI4736 + tremelimumab combination therapy compared to SoC using the EORTC 30-item Core QLQ-C30 version 3 and the 35-item Head and Neck QLQ H&N35 module
To assess the PK of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy
To investigate the immunogenicity of MEDI4736 and tremelimumab
To assess the safety and tolerability profile of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy compared to SoC in the first-line setting for treatment of SCCHN |
Eval. efic. del tto. de comb. MEDI4736 + tremel. en comp. con el TdR en térm. de SLP, TRO, DdR, VLP12, SLP2, SG y SG24.
Eval. efic. de MEDI4736 en monot. en comp. con el TdR en térm. de SLP, TRO, SLP2, SG y SG24.
Eval. efic. del tto. de comb. MEDI4736 + tremel. en comp. con MEDI4736 en monot. en térm. de SLP, TRO y SG.
Eval. sínt. relac. con la enf. y la calidad de vida relac. con la salud en pac. tratados con el tto. de comb. MEDI4736 + tremel. en comp. con el TdR usando Cuest. Básico de Calidad de Vida de 30 apart. (QLQ-C30) de la Org. Eur. para Invest. y el Tto. del Cáncer (EORTC), vs 3, y el mód. del Cuest. de Calidad Vida Cáncer de Cabeza y Cuello de 35 apartados (QLQ-H&N35).
Evaluar la FC del tto. de comb. MEDI4736 + tremel. y de MEDI4736 en monot.
Invest. la inmunog. de MEDI4736 y tremel.
Eval. perfil de seg. y tolerab. del tto. de comb. de MEDI4736 + tremel. y de MEDI4736 en monot. en comp. con el TdR en el contexto de primera línea para el tto. del CCECC. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age > o = 18 years at the time of screening
2. Documented evidence of SCCHN (oral cavity, oropharynx, hypopharynx, or larynx).
3. A fresh tumor biopsy for the purpose of screening or an available archival
tumor sample.
4. No prior systemic chemotherapy for recurrent or metastatic disease
5. World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment
6. No prior exposure to immune-mediated therapy |
1. Edad > o = 18 años en el momento de la selección
2. CCECC (de cavidad oral, orofaringe, hipofaringe o laringe).
3. Las lesiones tumorales empleadas para las biopsias de reciente adquisición no deben ser las mismas lesiones empleadas como lesiones diana RECIST 1.1, a menos que no haya otras lesiones disponibles para biopsia.
4. Ninguna quimioterapia sistémica previa para enfermedad recurrente o metastásica
5. Estado funcional de la Organización Mundial de la Salud (OMS)/ECOG de 0 ó 1 al reclutamiento
6.Los pacientes no deben haber tenido exposición previa a tratamiento mediado por el sistema inmunitario |
|
| E.4 | Principal exclusion criteria |
1. Received any systemic therapy for recurrent or metastatic SCCHN
2. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn?s disease], diverticulitis |
1. El paciente ha recibido cualquier tratamiento sistémico para CCECC recurrente o metastásico
2. Progresión o recidiva tumoral dentro de un plazo de 6 meses después de la última dosis de tratamiento con platino en el contexto del tratamiento primario
3. Recepción de cualquier radioterapia o tratamiento hormonal para el cáncer dentro de los 30 días previos a la primera dosis del tratamiento del ensayo
4. Trastornos autoinmunitarios o inflamatorios documentados activos o previos (como enfermedad inflamatoria intestinal [p. ej., colitis, enfermedad de Crohn], diverticulitis. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Co-primary: PFS using the Investigator?s assessments according to RECIST 1.1, and OS |
| Coprincipial: SLP usando las evaluaciones por el investigador de acuerdo con los RECIST 1.1 SG |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| PFS - At baseline, after that every 6 weeks for the first 24 weeks relative to the date of randomization, and then every 8 weeks until progression. |
| SLP - Cada 6 semanas durante las primeras 24 semanas, luego cada 8 semanas en adelante (en relación con la fecha de aleatorización). |
|
| E.5.2 | Secondary end point(s) |
PFS in patients with PD-L1-negative SCCHN using Investigator assessments according to RECIST 1.1
OS in patients with PD-L1-negative SCCHN
ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1
PFS2 using local standard clinical practice
OS24
EORTC QLQ-C30
EORTC QLQ-H&N35
Changes in World Health Organization/Eastern Cooperative Oncology Group performance status
Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK parameters, such as peak concentration and trough
Presence of ADAs for MEDI4736 and tremelimumab |
SLP en pacientes con CCECC negativo para PD-L1 usando las evaluaciones por el investigador de acuerdo con los RECIST 1.1.
SG en pacientes con CCECC negativo para PD-L1
TRO, DdR y VLP12 usando las evaluaciones por el investigador de acuerdo con los RECIST 1.1
SLP2 según la práctica clínica habitual local
SG24
QLQ-C30 de la EORTC
QLQ-H&N35 de la EORTC
Cambios en el estado funcional de la Organización Mundial de la Salud /Eastern Cooperative Oncology Group
Concentración de MEDI4736 y tremelimumab en sangre y parámetros FC no compartimentales, como la concentración máxima y en el valle
Presencia de AAF frente a MEDI4736 y tremelimumab |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS - At baseline, after that every 6 weeks for the first 24 weeks relative to the date of randomization, and then every 8 weeks until progression.
EORTC QLQ-C30- Every 4 weeks for the first 12 weeks relative to the date of randomization, then every 8 weeks thereafter.
EORTC QLQ-H&N35 - Every 2 weeks for the first 12 weeks relative to the date of randomization, then every 4 weeks thereafter. |
SLP - Cada 6 semanas durante las primeras 24 semanas, luego cada 8 semanas en adelante (en relación con la fecha de aleatorización) .
QLQ-C30 - Cada 4 semanas durante las primeras 12 semanas en relación con la fecha de aleatorización, luego cada 8 semanas en adelante
CQLQ-H&N35 - Cada 2 semanas durante las 12 primeras semanas respecto a la fecha de aleatorización, después cada 4 semanas en adelante |
|
| 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) | 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Cetuximab + Platinum (cisplatino o carboplatino) + 5FU |
| Cetuximab + Platinum (Cisplatin or Carboplatin) + 5FU |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| 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 |
| Brazil |
| Canada |
| France |
| Germany |
| Greece |
| India |
| Italy |
| Japan |
| Korea, Democratic People's Republic of |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Slovakia |
| Spain |
| Taiwan |
| Thailand |
| Ukraine |
| United Kingdom |
| United States |
| Vietnam |
|
| 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
|
| LVLS |
| Última visita del último paciente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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