E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III non-small cell lung cancer |
Carcinoma polmonare non a piccole cellule in stadio III |
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E.1.1.1 | Medical condition in easily understood language |
Non-small cell lung cancer |
Carcinoma polmonare non a piccole cellule |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Clinical activity - To compare the antitumor activity of durvalumab alone vs durvalumab in combination with novel agents. |
Attività clinica - Confrontare l'attività antitumorale di durvalumab in monoterapia rispetto a durvalumab, in combinazione con nuovi agenti |
|
E.2.2 | Secondary objectives of the trial |
Safety - To evaluate the safety and tolerability of durvalumab alone and durvalumab in combination with novel agents. Clinical activity - To further compare the efficacy of durvalumab alone vs durvalumab in combination with novel agents. Pharmacokinetics (a) To describe the pharmacokinetics (PK) of durvalumab alone and durvalumab in combination with novel agents. (b) To describe the PK of novel agents in combination with durvalumab. Immunogenicity (a) To assess the immunogenicity of durvalumab alone or in combination with novel agents (b) To assess the immunogenicity of novel biologic agents in combination with durvalumab |
Sicurezza - Valutare la sicurezza e la tollerabilità di durvalumab in monoterapia e durvalumab in combinazione con nuovi agenti Attività clinica - Confrontare ulteriormente l'efficacia di durvalumab in monoterapia rispetto a durvalumab in combinazione con nuovi agenti Farmacocinetica (a) Descrivere la farmacocinetica (PK) di durvalumab in monoterapia e di durvalumab in combinazione con nuovi agenti (b) Descrivere la PK di nuovi agenti in combinazione con durvalumab Immunogenicità (a) Valutare l'immunogenicità di durvalumab in monoterapia o in combinazione con nuovi agenti (b) Valutare l'immunogenicità di nuovi agenti biologici in combinazione con durvalumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation 2. Age 18 years or older 3. Body weight = 35 kg 4. Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease 5. Subjects must have completed, without progressing, definitive cCRT within 28 days prior to being randomized into the study. 6. Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1 7. Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy 8. Life expectancy = 12 weeks 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 |
1. Consenso informato scritto e qualsiasi autorizzazione richiesta a livello locale ottenuta dal soggetto prima dell’esecuzione di qualsiasi procedura correlata al protocollo, ivi compresa la valutazione di screening 2. Età pari a o maggiore di 18 anni 3. Peso corporeo = 35 kg 4. I soggetti devono presentare NSCLC istologicamente o citologicamente documentato con malattia localmente avanzata, non resecabile, di Stadio III 5. I soggetti devono aver portato a termine la cCRT definitiva, senza progressione, 28 giorni prima della randomizzazione nello studio 6. I soggetti devono presentare almeno una lesione tumorale sottoposta a pregressa radioterapia, misurabile secondo i criteri RECIST v1.1 7. Fornitura del campione di tessuto tumorale, quando disponibile, risalente alla prima diagnosi ottenuta prima dell’instaurazione di radio-chemioterapia 8. Aspettativa di vita = 12 settimane 9. Stato di performance di 0 o 1 nella scala Gruppo cooperativo orientale di oncologia (ECOG) |
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E.4 | Principal exclusion criteria |
1. Mixed small cell and non-small cell lung cancer histology 2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. 3. Subjects with history of = Grade 2 pneumonitis from prior chemoradiation therapy 4. Subjects with a history of venous thrombosis within the past 3 months 5. Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months 6. Congestive heart failure 7. Active or prior documented autoimmune or inflammatory disorders 8. History of active primary immunodeficiency 9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) 10. History of allogenic organ transplantation 11. QTcF interval = 470 ms 12. History of another primary malignancy 13. Concurrent enrollment in another therapeutic clinical study or during the follow-up period of an interventional study. Enrollment in observational studies will be allowed 14. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study |
1. Carcinoma polmonare dall’istologia mista a piccole cellule e non a piccole cellule 2. Impiego attuale o pregresso di farmaci immunosoppressori nei 14 giorni precedenti alla somministrazione della prima dose del farmaco in studio 3. Soggetti con anamnesi di polmonite di grado = 2 da pregressa radio-chemioterapia 4. Soggetti con anamnesi di trombosi venosa nei 3 mesi precedenti 5. Soggetti con anamnesi di infarto del miocardio, attacco ischemico transitorio o ictus nei 6 mesi precedenti 6. Insufficienza cardiaca congestizia 7. Patologie autoimmuni o infiammatorie attive o pregresse 8. Anamnesi di immunodeficienza primaria attiva 9. Infezione attiva, tra cui tubercolosi, epatite B, epatite C o virus dell’immunodeficienza umana (HIV) 10. Anamnesi di trapianto d’organo allogenico 11. Intervallo QTcF = 470 ms 12. Anamnesi di altra malignità primaria 13. Arruolamento concomitante in altro studio clinico terapeutico o durante il periodo di follow-up di uno studio interventistico. L’arruolamento in studi osservazionali sarà consentito 14. Donne incinte, che stanno allattando o che intendono intraprendere una gravidanza durante la partecipazione allo studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical activity - Objective response (OR) per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1) |
Attività clinica - Risposta obiettiva (OR) secondo i Criteri di valutazione della risposta nei tumori solidi versione 1.1 (RECIST v1.1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization until documention of disease progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first. |
Dalla randomizzazione alla documentazione di progressione della malattia o all’ultima valutazione utile della malattia in assenza di PD prima dell’inizio della successiva terapia antitumorale o dell’interruzione dello studio, in base all’evento che si verifica prima. |
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E.5.2 | Secondary end point(s) |
Safety - Presence of adverse events (AEs), serious adverse events (SAEs), and abnormal laboratory parameters and vital signs. Clinical activity - Duration of response (DoR), disease control (DC), progression-free survival (PFS) at 12 months, and PFS per RECIST v1.1 and overall survival (OS). Pharmacokinetics - Concentration of durvalumab or novel agents in serum. Immunogenicity - Antidrug antibody (ADA) incidence of durvalumab or novel biologic agents |
Sicurezza - Presenza di eventi avversi (EA), eventi avversi seri (EAS), anomalie nei parametri di laboratorio e nei segni vitali.
Attività clinica - Durata della risposta (DoR), controllo della malattia (DC), sopravvivenza libera da progressione (PFS) a 12 mesi, PFS secondo i criteri RECIST v1.1 e sopravvivenza complessiva (OS).
Farmacocinetica - Concentrazione di durvalumab o di nuovi agenti nel siero.
Immunogenicità - Incidenza di anticorpi anti-farmaco (ADA) di durvalumab o di nuovi agenti biologici. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety - From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment.
DoR - From randomization until documention of disease progression.
DC - From randomization until progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first.
PFS and OS - From start of treatment until study completion or death, whichever comes first.
Pharmacokinetics and immunogenicity - During the treatment period and follow-up. |
Sicurezza - Dal momento del consenso informato per l’intero periodo di trattamento (12 mesi) o fino a 3 mesi dopo la somministrazione dell’ultima dose di trattamento in studio.
DoR - Dalla randomizzazione alla documentazione di progressione della malattia.
DC - Dalla randomizzazione alla progressione o all’ultima valutazione utile della malattia in assenza di PD prima dell’inizio della successiva terapia antitumorale o dell’interruzione dello studio, in base all’evento che si verifica prima.
PFS e OS - Dall’inizio del trattamento al completamento dello studio o al decesso, in base all’evento che si verifica prima.
Farmacocinetica e immunogenicità - Durante il periodo di trattamento e follow-up. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Immunogenicità |
|
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Studio su piattaforma |
Platform study |
|
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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Canada |
Hong Kong |
Taiwan |
United States |
France |
Germany |
Italy |
Poland |
Portugal |
Spain |
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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
|
The end of the study ("study completion") is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This date will be 5 years after the final subject is entered into the study or when the sponsor stops the study, whichever occurs first. |
Con fine dello studio (“completamento dello studio”) si denota la data dell’ultima valutazione/visita specificata nel protocollo (con indicazione di recapito telefonico) per l’ultimo soggetto partecipante allo studio. Tale data sarà 5 anni dopo l’ingresso dell’ultimo soggetto o quando lo sponsor interrompe lo studio, in base all’evento che si verifica prima. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |