E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Small cell lung cancer (SCLC) |
carcinoma polmonare a piccole cellule in stadio esteso, microcitoma (SCLC) |
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E.1.1.1 | Medical condition in easily understood language |
SCLC is a disease in which cancer cells form in tissues of the lung. |
SCLC è una malattia in cui si formano cellule tumorali nei tessuti polmonari. |
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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 | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10041067 |
E.1.2 | Term | 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 evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) on the basis of progression free survival (PFS) and overall survival (OS) in primary population (PP, patients without present or history of brain metastases at baseline). |
valutare l’efficacia di tiragolumab più atezolizumab più carboplatino ed etoposide (CE) rispetto a placebo più atezolizumab e CE in pazienti con carcinoma polmonare a piccole cellule in stadio esteso (ES-SCLC) non trattato sulla base dei seguenti endpoint co-primari: Sopravvivenza libera da progressione (PFS) e Sopravvivenza globale (OS) in pazienti randomizzati senza presenza o anamnesi di metastasi cerebrali al basale (Primary Population PP) |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of tiragolumab plus atezolizumab and CE compared with placebo plus atezolizumab and CE on the basis of PFS, OS in intent to treat (ITT) population, Confirmed objective response rate, duration of response, progression free survival at 6 months and at 12 months, overall survival rates at 12 months and 24 months and time to confirmed deterioration in the PP and ITT population • To evaluate the safety of tiragolumab plus atezolizumab and CE compared with placebo plus atezolizumab and CE • To characterize the pharmacokinetics of tiragolumab and atezolizumab • To evaluate the immune response to tiragolumab and atezolizumab |
-valutare l’efficacia di tiragolumab più atezolizumab e CE rispetto a placebo più atezolizumab e CE sulla base dei seguenti endpoint: PFS nella popolazione intent to treat (ITT), OS nella pop. ITT, tasso di risposta obiettiva (ORR) confermata in PP e nella pop. ITT che presenta malattia misurabile al basale, Durata della risposta (DOR) in PP e nella pop.ITT, tassi di PFS a 6 e 12 mesi nella PP e nella pop.ITT, Tassi di OS a 12 e 24 mesi nella PP e nella popolazione ITT, Tempo al peggioramento dell’attività fisica e delle condizioni generali di salute riferite dal paziente QoL(GHS/QoL) confermato in base al Quality of life Questionnaire Core (QLQ-C30) della EuropeanOrganization for the Research and Treatment of Cancer(EORTC) nellaPPenella popolazioneITT -valutare la sicurezza di tiragolumab più atezolizumab e CE rispetto a placebo più atezolizumab e CE -caratterizzare la farmacocinetica di tiragolumab e atezolizumab -valutare la risposta immunitaria a tiragolumab e atezolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - Eastern Cooperative Oncology Group performance status of 0 or 1 - Histologically or cytologically confirmed ES-SCLC - No prior systemic treatment for ES-SCLC - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 - Adequate hematologic and end-organ function |
-Età >=18 anni -Performance status secondo l’ECOG pari a 0 o 1 -ES-SCLC confermato dall’esame istologico o citologico -Nessun precedente trattamento sistemico per l’ES-SCLC -Malattia misurabile secondo i criteri RECIST v1.1 -Adeguata funzionalità ematologica, epatica e renale |
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E.4 | Principal exclusion criteria |
- Symptomatic or actively progressing CNS metastases - Leptomeningeal disease - Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome - Active or history of autoimmune disease or immune deficiency - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Severe infection at the time of randomization - Treatment with investigational agent within 28 days prior to initiation of treatment study - Current treatment with anti-viral therapy for HBV or HCV - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies - Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to randomization - Treatment with systemic immunosuppressive medications within 1 week prior to randomization or anticipation of need for systemic immunosuppressive medication during study treatment |
-Metastasi a carico del sistema nervoso centrale (SNC) sintomatiche o in progressione attiva. -Neoplasie maligne diverse dall’SCLC nei 5 anni precedenti la randomizzazione, fatta eccezione per quelle soggette a un rischio trascurabile di metastasi o decesso e trattate con intento curativo -Malattia autoimmune o immunodeficienza attiva o pregressa -Anamnesi positiva per fibrosi polmonare idiopatica, polmonite in organizzazione, polmonite indotta da farmaci o polmonite idiopatica, oppure evidenza di polmonite attiva alla TC del torace allo screening -Infezione severa al momento della randomizzazione -Trattamento con qualsiasi agente sperimentale nei 28 giorni precedenti l’inizio del trattamento sperimentale. -Trattamento in corso con una terapia antivirale per l’HBV o l’HCV -Precedente trattamento con agonisti di CD137 o terapie che bloccano i checkpoint immunitari, anticorpi terapeutici anti-CTLA-4, anti-TIGIT, anti PD-1 e anti PD-L1 -Trattamento con immunostimolanti sistemici nelle 4 settimane o nelle 5 emivite del farmaco precedenti la randomizzazione -Trattamento con immunosoppressori sistemici nella settimana precedente la randomizzazione o necessità prevista di immunosoppressori sistemici durante il trattamento in studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression-free survival in the PP 2. Overall survival in the PP |
1. Sopravvivenza libera da progressione (PFS) nella popolazione intent to treat (ITT) 2. Sopravvivenza globale (OS) nella popolazione ITT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 50 months |
1-2 fino a 50 mesi |
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E.5.2 | Secondary end point(s) |
1. Progression free survival in the ITT 2. Overall survival in the ITT 3. Confirmed objective response rate in the PP and ITT population 4. Duration of response in the PP and ITT population 5. Progression-free survival rates at 6 months and at 12 months in the PP and ITT population 6. Overall survival rates at 12 months and 24 months in the PP and ITT population 7. Time to confirmed deterioration in the PP and ITT population 8. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 9. Severity for cytokine-release syndrome (CRS) will also be determined according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS consensus grading scale 10. Minimum serum concentration [Cmin]of tiragolumab and atezolizumab at specified timepoints 11. Maximum serum concentration [Cmax] of tiragolumab and atezolizumab at specified timepoints 12. Prevalence of ADAs to tiragolumab and atezolizumab at baseline and during the study. |
1.PFS nella popolazione intent to treat (ITT) 2. OS nella popolazione ITT 3. Tasso di risposta obiettiva (ORR) confermata in PP e nella popolazione ITT che presenta malattia misurabile al basale 4. Durata della risposta (DOR) nella PP e nella popolazione ITT 5. Tassi di PFS a 6 e 12 mesi nella PP e nella popolazione ITT 6. Tassi di OS a 12 e 24 mesi nella PP e nella popolazione ITT 7. Tempo al peggioramento confermato nella PP e nella popolazione ITT 8. Incidenza e severità degli eventi avversi, con severità stabilita in base ai criteri comuni di terminologia per gli eventi avversi del National Cancer Institute (NCI), versione 5.0 (CTCAE v5.0) 9. La gravità della sindrome da rilascio di citochine (CRS) sarà anche determinata in accordo alla scala di valutazione dell'American Society for Transplantation and Cellular Therapy (ASTCT) 10. Concentrazione sierica minima di tiragolumab e atezolizumab a specifici timepoint 11. Concentrazione sierica massima di tiragolumab e atezolizumab a specifici timepoint. 12. Prevalenza di anticorpi anti-farmaco (ADA) diretti contro tiragolumab e atezolizumab al basale e e durante lo studio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-10. Up to 50 months |
1-10 fino a 50 mesi |
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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) | Yes |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 |
China |
Japan |
New Zealand |
Russian Federation |
Singapore |
Taiwan |
Turkey |
United States |
Austria |
Belgium |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
Switzerland |
United Kingdom |
Czechia |
Greece |
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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 study will occur when both of the following criteria have been met: - The last patient, last visit (LPLV) has occurred. - Approximately 288 deaths have been observed among randomized patients in the PP. Additionally, the Sponsor may decide to terminate the study at any time. If the Sponsor decides to terminate the study, patients who are still receiving study treatment or undergoing survival follow-up may be enrolled in an extension study. |
Lo studio si concluderà quando:• Sarà stata effettuata l’ultima visita dell’ultimo paziente (LPLV); • Saranno stati osservati circa 288 decessi nella PP. Lo Sponsor potrà inoltre decidere di interrompere la ricerca in qualsiasi momento. Se lo Sponsor deciderà di porre fine allo studio, i pazienti ancora in terapia con il trattamento in studio o sottoposti al follow-up per la sopravvivenza potranno essere arruolati in uno studio di estensione. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 50 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 50 |
E.8.9.2 | In all countries concerned by the trial days | 0 |