E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced squamous cell carcinoma of the head and neck (SCCHN) |
CARCINOMA A CELLULE SQUAMOSE DELLA TESTA E DEL COLLO LOCALMENTE AVANZATO |
|
E.1.1.1 | Medical condition in easily understood language |
Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells and develops in the mucous membranes (lining) of the different structures in the mouth, throat, and larynx |
IL CARCINOMA A CELLULE SQUAMOSE è TUMORE CHE SI ORIGINA DA PARTICOLARI CELLULE CHIAMATE SQUAMOSE E SI SVILUPPA NELLE MEMBRANE MUCOSE (FODERA) DI DIFFERENTI STRUTTURE IN BOCCA, COLLO E LARINGE |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
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 evaluate the efficacy of atezolizumab compared with placebo based on investigator assessed event free survival (EFS) and overall survival (OS) |
Valutare l'efficacia di atezolizumab rispetto al placebo sulla base della sopravvivenza libera da eventi (EFS) valutata dallo sperimentatore e della sopravvivenza globale (OS) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of atezolizumab compared with placebo based on independent review facility (IRF) assessed EFS - To evaluate clinical benefit in atezolizumab compared with placebo in terms of impact on health-related quality of life and physical functioning - To evaluate the safety and tolerability of atezolizumab - To characterize the pharmacokinetics of atezolizumab - To evaluate the incidence and titers of anti-drug antibody(ADA) against atezolizumab |
- Valutare l'efficacia di atezolizumab rispetto al placebo sulla base della sopravvivenza libera da eventi (EFS) valutata dalla struttura di revisione indipendente (IRF). - valutare il beneficio clinico di atezolizumab rispetto a placebo in termi di impatto sulla qualit¿ della vita correlata alla salute e funzionalità fisica - valutare la sicurezza e la tollerabilità di atezolizumab - caratterizzare la farmacocinetica di atezolizumab - valutare l'incidenza e i titoli di ADA diretti contro atezolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age >= 18 years - Ability to comply with the study protocol, in the investigator's judgment - Histologically or cytologically confirmed squamous cell carcinoma of the head and neck SCCHN - Human papillomavirus (HPV) status - Completed definitive local therapy - Absence of metastatic disease as documented by radiographic scans - Adequate hematologic and end-organ function - For patients receiving therapeutic anticoagulation: stable anticoagulant regimen - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of study treatment. Women must refrain from donating eggs during this same period - Confirmed response of CR, PR, or SD to definitive local therapy documented in radiographic scans = 8 weeks after completion of definitive local therapy |
Età >= 18 anni - Capacità di rispettare il protocollo dello studio secondo il giudizio dello sperimentatore. - SCCHN confermato dall’esame istologico o citologico - Stato HPV - Aver completato il trattamento locale definitivo - Assenza di malattia metastatica secondo quanto documentato dalle indagini radiografichei - Adeguata funzionalità ematologica e d’organo - Nei pazienti sottoposti a trattamento anticoagulante: regime anticoagulante stabile. - Nelle donne in età fertile: consenso a praticare l’astinenza dai rapporti eterosessuali o ad adottare metodi contraccettivi che garantiscano un tasso di insuccesso < 1% all’anno durante il periodo di trattamento e per 5 mesi dopo la somministrazione dell’ultima dose del trattamento in studio. Le donne dovranno astenersi dalla donazione di ovuli durante lo stesso periodo di tempo. - Risposta confermata di CR, PR o SD alla terapia locale definitiva documentata da TAC con contrasto o RMN con contrasto della regione della testa e del collo eseguita >= 8 settimane dopo il completamento della terapia locale definitiva |
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E.4 | Principal exclusion criteria |
- Patients who have received surgery alone or radiotherapy alone as definitive local therapy - Squamous cell carcinoma of the nasopharynx or paranasal sinuses or non-squamous histology - Evidence of disease progression or metastatic disease during or following definitive local therapy documented in the post-definitive local therapy screening scans - Uncontrolled or symptomatic hypercalcemia - Active or history of autoimmune disease or immune deficiency - Active tuberculosis - Significant cardiovascular disease - History of malignancy-, including prior SCCHN primary tumors (other than SCCHN) within 5 years prior to screening, patients who have malignancies of a negligible risk of metastasis or death are eligible - Prior allogeneic stem cell or solid organ transplantation - Current treatment with anti-viral therapy for HBV - Prior neoadjuvant (i.e., induction) treatment or any systemic anti-cancer therapy without definitive local therapy for locally advanced head and neck cancer - Treatment with systemic immunostimulatory agents - Treatment with systemic immunosuppressive - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins - Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment - Patients who have received a non-FDA or non-EMA approved anti-EGFR agent or any other non-FDA or non-EMA approved agent as part of concurrent radiotherapy - Any systemic therapy in the adjuvant setting such as after surgery, radiation, or concurrent chemoradiotherapy |
- Pazienti sottoposti alla sola chirurgia o alla sola radioterapia come trattamento locale definitivo - Carcinoma rinofaringeo a cellule squamose o sinusite paranasale o istologia non squamosa - Evidenze di progressione della malattia o malattia metastatica durante o dopo il trattamento locale definitivo, documentate alle indagini radiologiche di screening effettuate post-trattamento locale definitivo - Ipercalcemia non controllata o sintomatica - Anamnesi presente o pregressa di malattia autoimmune o immunodeficienza - Tubercolosi attiva - Cardiovasculopatia significativa - Anamnesi di neoplasia maligna inclusi precedenti tumori primari SCCHN (diversi dal presente SCCHN) nei 5 anni precedenti lo screening, fatta eccezione per quelle soggette a un rischio trascurabile di metastasi o decesso - Precedente trapianto allogenico di cellule staminali o di organi solidi - Trattamento in corso con una terapia antivirale per HBV - Precedente trattamento neoadiuvante (per es. induzione) o terapia antitumorale sistemica senza trattamento locale definitivo per carcinoma della testa e del collo localmente avanzato - Trattamento con immunostimolanti sistemici - Trattamento con immunosoppressori sistemici - Anamnesi di reazioni allergiche anafilattiche severe agli anticorpi chimerici o umanizzati,o alle proteine di fusione - Gravidanza o allattamento o intenzione di iniziare una gravidanza durante il trattamento in studio o nei 5 mesi successivi alla somministrazione dell’ultima dose del trattamento in studio - Pazienti che abbiano ricevuto un agente anti-EGFR o un qualsiasi altro agente,come parte della radioterapia concomitante,non approvato da FDA o da EMA - Qualsiasi terapia sistemica nel trattamento adiuvante dopo la chirurgia, la radioterapia o la CRT concomitante. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Investigator-assessed EFS 2. OS after randomization |
1. EFS valutata dallo sperimentatore 2. OS dopo la randomizzazione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Approximately up to 110 months |
1-2. Approssimativamente fino a 110 mesi |
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E.5.2 | Secondary end point(s) |
1. IRF-assessed EFS 2. Change from baseline in physical function and Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer (EEORTC) Quality of Life Questionnaire over time while receiving treatment 3. Percentage of patients with adverse events 4. Serum concentration of atezolizumab at specified timepoints 5. Incidence of ADA response to atezolizumab |
1. EFS valutata dalla struttura di revisione indipendente 2. Variazione della funzionalità fisica nel tempo rispetto al basale durante il trattamento, valutata mediante l’uso della sottoscala relativa alla funzionalità fisica a cinque voci del questionario EORTC QLQ-C30 3. Percentuale di pazienti che presentano ecenti avversi 4. Concentrazione sierica di atezolizumab a scadenze prestabilite 5. Incidenza della risposta ADA ad atezolizumab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Approximately up to 110 months 2. Baseline up until 30 days from last dose 3. Baseline until up to 90 days after end of treatment (approximately 1 year) 4-5. At pre-defined intervals from Cycle 1, Day 1, through end of treatment (approximately 1 year) |
1. Approssimativamente fino a 110 mesi 2. Dal basale fino a 30 giorni dall’ultima dose 3. Dal basale fino a 90 giorni dalla fine del trattamento 4-5. A intervalli predefiniti dal ciclo 1, gioro 1, alla fine del trattamento (approssimativamente 1 anno) |
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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 | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 | Information not present in EudraCT |
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 |
Brazil |
Canada |
China |
India |
Korea, Republic of |
Russian Federation |
South Africa |
Taiwan |
Ukraine |
United States |
France |
Germany |
Italy |
Poland |
Spain |
United Kingdom |
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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
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The end of this study is defined as the date when all patients meet one of the following criteria: experienced an OS event, become lost to follow-up, withdrawn consent, or completed at least 60 months of follow-up after randomization, whichever occurs first. In addition, the Sponsor
may decide to terminate the study at any time. |
La fine dello studio coincider¿ con la data in cui tutti i pazienti soddisferanno uno dei seguenti criteri: manifestazione di un evento di OS, perdita al follow-up, revoca del consenso o completamento di almeno 60 mesi di follow-up dopo la randomizzazione, a seconda di quale evento si verifichi per primo. Lo Sponsor potr¿ inoltre decidere di interrompere la ricerca in qualsiasi momento. |
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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 | 7 |
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 | 9 |
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 |