E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with unresected Stage I/II, lymph-node negative Non-small Cell Lung Cancer |
Pazienti con tumore al polmone non a piccole cellule al I/II stadio, non operabile, linfonodo negativo |
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E.1.1.1 | Medical condition in easily understood language |
Specific type of lung cancer called "Non-Small Cell Lung Cancer" |
Tipologia specifica di tumore polmonare chiamata "Carcinoma Polmonare Non a Piccole Cellule" (NSCLC). |
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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 | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS in patients with T1c to T3N0M0 NSCLC |
Valutare l’efficacia della monoterapia a base di Durvalumab rispetto al placebo in termine di PFS nei pazienti con T1c a T3N0M0 (NSCLC) |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS for all stage I/II NSCLC patients To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS in patients with subset of T1-T3N0 NSCLC To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS in patients with Stage I/II NSCLC To further assess the efficacy of durvalumab monotherapy compared to placebo in terms of lung cancer-specific mortality To further assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS24, TTP, TTDM, and PFS2 To assess the PK of durvalumab To investigate the immunogenicity of durvalumab To assess symptoms and health-related quality of life in patients treated with durvalumab monotherapy compared to placebo using the EORTC QLQ-C30 To assess the safety and tolerability profile of durvalumab monotherapy compared to placebo after administration of SBRT |
Valutare l’effic della monot a base di Durvalumab rispetto al placebo in termine di PFS nei pazienti con NSCLC al I/II stadio Valutare l’effic della monot a base di Durvalumab rispetto al placebo in termine di OS in pazienti con subset T1-T3N0 (NSCLC). Valutare l’effic della monot a base di Durvalumab rispetto al placebo in termini di OS in paz con NSCLC al I/II stadio. Valutare l’effic della monot a base di Durvalumab rispetto al placebo in termini di mortalità specifica per tumore al polmone Valutare l’effic della monot a base di Durvalumab rispetto al placebo in termini di PFS24, TTP, TTDM ePFS2 Valutare la farmacocinetica (PK) di Durvalumab Valutare l’immunogenicità di Durvalumab Valutare i sintomi e QOL relativa alla salute nei pazienti trattati con la monot a base di durvalumab rispetto al placebo utilizzando il EORTC QLQ-C30 Valutare i profili di sicurezza e di tollerabilità della monoterapia a base di Durvalumab rispetto al placebo dopo la somministrazione di SBRT. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age =18 years 2. Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive treatment with SBRT. Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy 3. Completion of SoC SBRT as definitive treatment prior to randomization 4. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1, or 2 5. Life expectancy of at least 12 weeks 6. Body weight >30 kg 7. Submission of available tumor tissue sample 8. Adequate organ and marrow function required 9. Patients with central or peripheral lesions are eligible 10. Staging studies must be done within 10 weeks before randomization 11. Pulmonary Function Testing within 12 weeks of randomization 12. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated definitively with radiation, surgery only, or surgery with adjuvant chemotherapy in whom all treatments completed >1 year prior to randomization are eligible. |
1. Età =18 anni 2. NSCLC Stadio I / II confermato attraverso esame istologico o citologico, con stadiazione clinica I/II linfonodo negativo e grado di malattia compreso tra T1 e T3N0M0 candidati a ricevere il trattamento con radioterapia sterotassica corporea (SBRT). Pazienti che sono clinicamente inoperabili o che sono clinicamente operabili ma che hanno rifiutato la chirurgia o che hanno scelto la SBRT come terapia definitiva 3. Completamento della SBRT (trattamento standard) come trattamento definitivo prima della randomizzazione 4. Performance status (PS) del World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) di 0, 1 o 2 all’arruolamento ed alla randomizzazione 5. Aspettativa di vita di almeno 12 settimane 6. Peso corporeo >30 kg 7. Consegna di un campione disponibile del tumore 8. Adeguata funzionalità degli organi e del midollo osseo 9. Sono eleggibili pazienti con lesioni centrali o periferiche 10. Gli esami per determinare la stadiazione devono essere fatti entro 10 settimane prima della randomizzazione 11. Test di funzionalità polmonare entro 12 settimane dalla randomizzazione 12. Pazienti con una storia di metacronus in stadio I / II (T1-T3N0M0) NSCLC trattato in modo definitivo con radioterapia, solo chirurgia o chirurgia con chemioterapia adiuvante in cui tutti i trattamenti sono stati completati più di 1 anno prima alla randomizzazione sono eleggibili. |
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E.4 | Principal exclusion criteria |
1. Mixed small cell and non-small cell cancer histology 2. History of allogeneic organ transplantation 3. History of another primary malignancy with exceptions 4. History of active primary immunodeficiency 5. Any unresolved toxicity National Cancer Institute (NCI) CTCAE Grade=2 from SBRT (Stereotactic Body Radiation Therapy) |
1. Istologia del tumore mista a piccole cellule e non a piccole cellule 2. Storia di trapianto allogenico 3. Storia di un altro tumore primario senza eccezioni 4. Storia di un'immunodeficienza primaria attiva 5. Qualsiasi tossicità, non risolta dovuta alla SBRT di grado = 2 riportato dal National Cancer Institute (NCI) CTCAE, SBRT (Radioterapia stereotassica corporea) |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS in patients with subset of T1-T3N0 by BICR |
PFS in pazienti con sottotipo T1 a T3N0 secondo BICR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On-study tumor assessments occur 8 weeks after randomization, then every 12 weeks through week 116, then every 16 weeks through 3 years after randomization, then every 6 months thereafter until objective disease progression. |
Le valutazioni del tumore si verificano 8 settimane dopo la randomizzazione, poi ogni 12 settimane fino alla 116ª settimana, poi ogni 16 settimane fino a 3 anni dopo la randomizzazione, e poi ogni 6 mesi fino a progressione |
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E.5.2 | Secondary end point(s) |
- PFS in patients with T1 to T3N0 NSCLC - OS in patients with subset of T1-T3N0 NSCLC - OS in patients with T1 to T3N0M0 NSCLC - Lung cancer mortality - PFS24, TTP, and TTDM using BICR assessments according to RECIST 1.1 - PFS2 using local assessment - Concentration of durvalumab in blood - Presence of ADA for durvalumab - EORTC QLQ-C30: Change in symptoms, functioning and global health status/quality of life - Safety and tolerability: AEs, physical examinations, vital signs, electrocardiograms, and laboratory findings |
- PFS in pazienti con NSCLC da T1 a T3N0 - OS in pazienti con sottotipo NSCLC da T1 a T3N0 - OS in pazienti con NSCLC da T1 a T3N0M0 - Mortalità del tumore al polmone - PFS24, TTP, and TTDM usando valutazioni BICR in base ai criteri RECIST 1.1 - PFS2 con l’utilizzo della valutazione locale - Concentrazione di durvalumab nel sangue - Presenza di ADA per durvalumab - EORTC QLQ-C30: Cambiamenti nei sintomi, funzionalità e stato/qualità della vita globale - Sicurezza e Tollerabilità: eventi avversi, esami fisici, segni vitali, elettrocardiogrammi ed esami di laboratorio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS: from randomization until death due to any cause Lung cancer mortality: time from randomization until death due to lung cancer. PFS24: 24 months TTP: time from randomization until progression (excluding deaths) TTDM: time from randomization until death or distant metastasis PFS2: Time from randomization to second progression (local assessment) ADA: will be collected at Baseline, at Cycles: 1, 8, 14, 26 then months 3 and 6 after completed/discontinued study treatment EORTC QLQ-C30: Screening, at Baseline, Week 2, 4, 6, 8, 12, 16 and 20 weeks after randomization, then every 8 weeks until 3 years after randomization, then every 6 months until PFS2 Safety and tolerability - from randomization until 3 months after treatment discontinuation |
OS: dalla randomizzazione fino alla morte per qualsiasi causa Mortalità per carcinoma polmonare: tempo dalla randomizzazione fino alla morte per tumore polmonare PFS24: 24 mesi TTP: tempo dalla randomizzazione fino alla progressione (esclusi i decessi) TTDM: tempo dalla randomizzazione alla morte o metastasi distanti PFS2: tempo dalla randomizzazione alla seconda progressione (valutazione locale) - ADA: saranno raccolti al baseline, ai cicli: 8, 14, 20, 26 successivamente dopo 3 e 6 mesi dopo il completamento/discontinuazione dal trattamento - EORTC QLQ-C30: Screening al baseline, settimana 2, 4, 6, 8, 12, 16 e 20 settimane dopo la randomizzazione, poi ogni 8 settimane fino 3 anni dopo la randomizzazione, successivamente ogni 6 mesi fino PFS2 - |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability Symptoms and health-related quality of life Healthcare resource utilization |
Tollerabilità, Sintomi e qualità della vita correlati alla salute, Utilizzo di risorse sanitarie |
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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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Belgium |
Canada |
China |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Spain |
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
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Last expected visit/contact of the last patient undergoing the study (last subject last visit) |
Ultima visita prevista / contatto dell'ultimo paziente sottoposto allo studio (ultimo soggetto all'ultima visita) |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |