E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Small-Cell Lung Cancer |
TUMORE POLMONARE A PICCOLE CELLULE |
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E.1.1.1 | Medical condition in easily understood language |
Small cell lung cancer is a disease in which malignant rapidly dividing cancer cells form in the tissues of the lung |
TUMORE POLMONARE A PICCOLE CELLULE IN STADIO ESTESO |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 lurbinectedin in combination with atezolizumab compared with atezolizumab based on Independent Review Facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS) |
Valutare l’efficacia di lurbinectedina in associazione ad atezolizumab rispetto ad atezolizumab basata su IRF, Sopravvivenza libera da progressione (PFS) e Sopravvivenza globale (OS) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of lurbinectedin in combination with atezolizumab compared with atezolizumab based on Investigator-assessed PFS, Confirmed objective response rate (ORR), duration of response (DOR), PFS rates at 6 months and 12 months, and overall survival (OS) rates at 12 months and 24 months • To evaluate the safety of lurbinectedin in combination with atezolizumab compared with atezolizumab based on incidence and severity of adverse events • To evaluate the immunogenicity of atezolizumab with and without lurbinectedin based on the prevalence of anti-drug antibodies (ADA) to atezolizumab throughout treatment • To evaluate the health-related quality of life of participants treated with lurbinectedin in combination with atezolizumab compared with atezolizumab
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-Valutare l’efficacia di lurbinectedina in associazione ad atezolizumab rispetto ad atezolizumab, basata su PFS valutata dallo sperimentatore, Tasso di risposta obiettiva (ORR) confermata, durata del responso (DOR), Tassi di PFS a 6 e 12 mesi,Tassi di OS a 12 e 24 mesi -Valutare la sicurezza di lurbinectedina in associazione ad atezolizumab rispetto ad atezolizumab, basata su incidenza e severità degli eventi avversi -Valutare l’immunogenicità di atezolizumab con e senza lurbinectedina, basata sulla prevalenza di ADA diretti contro atezolizumab al basale della fase di induzione e incidenza di ADA diretti contro atezolizumab dopo la somministrazione del farmaco per gruppo di trattamento -Valutare la qualità di vita correlata alla salute dei partecipanti trattati con lurbinectedina in associazione ad atezolizumab rispetto ad 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 (ECOG) performance status (PS) of 0 or 1 • Histologically or cytologically confirmed ES-SCLC (per the modified VALG staging system) • No prior systemic treatment for ES-SCLC • Adequate hematologic and end-organ function to receive 4 cycles of induction treatment with carboplatin, etoposide and atezolizumab • Measurable disease, as defined by RECIST v1.1 • Submission of pre-induction therapy tumor sample for exploratory biomarker research • Negative HIV test and no evidence of active Hepatitis B or Hepatitis C at screening • Remain abstinent or use contraception and refrain from donating eggs (women) or donating sperm (men)
Inclusion Criteria for the Maintenance Phase • ECOG performance status (PS) of 0 or 1 • Ongoing response or stable disease per RECIST v1.1 after completion of the induction therapy • Randomized within 5 weeks (35 days) from last dose of induction therapy, or if receiving PCI, randomized within 9 weeks (63 days) from last dose of induction therapy • Toxicities attributed to prior induction anti-cancer therapy or PCI resolved to Grade <=1Adequate hematologic and end-organ function • For participants not receiving therapeutic anticoagulation: INR and aPTT <= 1.5 x ULN |
•Età >= 18 anni • Eastern Cooperative Oncology Group (ECOG) performance status (PS) di 0 o 1 • ES-SCLC istologicamente o citologicamente confermato • Nessun precedente trattamento sistemico per ES-SCLC • Adeguata funzione ematologica e degli organi per ricevere 4 cicli di trattamento di induzione con carboplatino, etoposide e atezolizumab • Malattia misurabile, come definito da RECIST v1.1 • sottomissione di campione tumorale di terapia pre-induzione per ricerca esploratoria dei biomarker • HIV test negativo e nessuna evidenza di Epatite B o Epatite C attiva allo screening • Astinenza o utilizzo di metodi contraccettivi es astenersi dal donare ovuli (donne) o donare sperma (uomini)
Criteri di inclusione per la fase di mantenimento: • ECOG performance status (PS) di 0 o 1 • Rsiposta ongoing o malattia stabile per RECIST v1.1 dopo il completamento della terapia di induzione • Randomizzato entro 5 settimane (35 giorni) dall'ultima dose della terapia di induzione, o se ricevente PCI, randomizzato entro 9 settimane (63 giorni) dall'ultima dose della terapia di induzione • Tossicità attribuita a precedente terapia antitumorale o PCI risolta di grado <=1 Adeguata funzionalità ematologica e degli organi • Per partecipanti che non ricevono terapia anticoagulante: INR and aPTT <= 1.5 x ULN |
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E.4 | Principal exclusion criteria |
• Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the final dose of study treatment • CNS metastases • Planned consolidative chest radiation • Uncontrolled tumor-related pain • Lesions requiring palliative radiotherapy • Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures • Active or history of autoimmune disease or deficiency • Clinically significant liver disease • History of malignancies other than SCLC within 5 years prior to enrollment • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, or lurbinectedin or trabectedin • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan • Treatment with investigational therapy within 28 days prior to enrollment
Exclusion Criteria for the Maintenance Phase • CNS metastases • Receiving consolidative chest radiation • Lesions that require palliative radiotherapy • Severe infection within 2 weeks prior to randomization into maintenance phase • Major surgical procedure, other than for diagnosis, within 4 weeks prior to randomization • Treatment with therapeutic oral or IV antibiotics at the time of randomization
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• partecipanti in gravidanza o in allattamento, o che intendono avviare una gravidanza durante lo studio o nei 6 mesi successivi alla dose finale di trattamento in studio • metastasi al CNS • Radiazioni al petto pianificate consolidative • Dolore tumore correlato non controllato • lesioni richiedenti radioterapia palliativa • Effusione pleurale non controllata, effusione pericardiale o asciti che richiedano procedure di drenaggio ricorrente • Malattia autoimmune attiva o storia di malattia autoimmune o immunodeficienza • malattia epatica clinicamente significativa • Storia di patologie maligne oltre a SCLC nei 5 anni precedenti l'arruolamento • Trattamento precedente con agonisti del CD137 o terapie bloccanti immune checkpoint,incluso anti-CTLA-4, anti-PD-1, e anti-PD-L1 anticorpi terapeutici, o lurbinectedin o trabectedin • Storia di fibrosi idiopatica polmonare, polmoniti indotte da farmaco, o idiopatiche, o evidenza di polmonite attiva al CT scan • Trattamento con un farmaco sperimentale nei 28 giorni precedenti l'arruolamento
Criteri di esclusione per la fase di mantenimento: • metastasi al CNS • Radiazioni al petto pianificate consolidative • lesioni richiedenti radioterapia palliativa • Infezione severa nelle 2 settimane precedenti la randomizzazione alla fase di mantenimento • Trattamento chirurgico maggiore, oltre a quello per la diagnosi, nelle 4 settimane precedenti la randomizzazione • Trattamento terapeutico con antibiotici per via orale o IV al tempo della randomizzazione |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. IRF-assessed progression-free survival (PFS) defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, or death from any cause (whichever occurs first) 2. Overall Survival defined as the time from randomization to death from any cause
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-Sopravvivenza libera da progressione (PFS) valutata dall’IRF, intesa come il tempo intercorso dalla randomizzazione alla prima comparsa di progressione della malattia, secondo quanto stabilito dall’IRF in funzione dei criteri RECIST v1.1, o al decesso per qualsiasi causa (a seconda della circostanza che si verifichi per prima) - Sopravvivenza globale (OS), intesa come il tempo intercorso dalla randomizzazione al decesso per qualsiasi causa |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 52 months |
1-2. fino a 52 mesi |
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E.5.2 | Secondary end point(s) |
1. Investigator-assessed progression-free survival (PFS) 2. Confirmed objective response rate (ORR) 3. Duration of response (DOR) 4. PFS rates at 6 months and 12 months 5. OS rates at 12 months and 24 months 6. Incidence and severity of adverse events, including serious adverse events and adverse events of special interest in randomized participants, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 7. Prevalence of anti-drug antibodies (ADAs) to atezolizumab at induction phase baseline and incidence of ADAs to atezolizumab after drug administration by treatment group 8. Time to confirmed deterioration (TTCD) from maintenance baseline in participant reported physical functioning and global health status as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
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1. Sopravvivenza libera da progressione (PFS) valutata dallo Sperimentatore 2. Tasso di risposta obiettiva (ORR) confermata 3.Durata della risposta (DOR) 4. Tasso di PFS a 6 mesi e a 12 mesi 5. Tasso di OS a 6 mesi e a 12 mesi 6. Incidenza e severità degli eventi avversi, compresi eventi avversi gravi e di interesse particolare, nei partecipanti randomizzati, con severità stabilita in funzione dei criteri NCI CTCAE v5.0 7. Prevalenza di ADA diretti contro atezolizumab al basale della fase di induzione e incidenza di ADA diretti contro atezolizumab dopo la somministrazione del farmaco per gruppo di trattamento 8. Tempo al peggioramento confermato (TTCD) dell’attività fisica e delle condizioni generali di salute riferite dal partecipante dal basale del mantenimento in funzione del questionario EORTC QLQ-C30 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to 52 months 4. At 6 months and 12 months after randomization 5. At 12 months and 24 months after randomization 6. Up to 52 months 7. Induction Phase: Day 1 of Cycle 1-4; Maintenance Phase: Day 1 of Cycle 1-4, 8, 12, and 16, </= 30 days after treatment discontinuation 8. Induction Phase: Day 1 of Cycle 1-4; Maintenance Phase: Day 1 of Cycle 1, <=30 Days after the last dose of study treatment, at treatment discontinuation visit, post treatment follow up visit
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1-3.fino a 52 mesi 4. A 6 mesi e 12 mesi dopo la randomizzazione 5. A 6 mesi e 24 mesi dopo la randomizzazione 6. fino a 52 mesi 7. Fase di induzione: Giorno 1 del Ciclo 1-4; Fase di mantenimento: Giorno 1 del Ciclo 1-4, 8, 12, e 16, </= 30 giorni dopo l'interruzione del trattamento 8. Fase di induzione:Giorno 1 del Ciclo 1-4; Fase di mantenimento: Giorno 1 del Ciclo 1, <=30 giorni dopo l'ultima dose del trattamento in studio, alla visita di interruzione del trattamento, alla visita di follow-up post trattamento |
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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 | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Germany |
Greece |
Hungary |
Italy |
Korea, Republic of |
Poland |
Russian Federation |
Spain |
Taiwan |
Ukraine |
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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last participant, last visit (LPLV) or the date at which the last data point required for statistical analysis (i.e., final OS analysis) or safety follow-up is received from the last participant, whichever occurs later. |
Ultimo partecipante, ultima visita (LPLV) o la data alla quale viene ricevuto l'ultimo dato dell'ultimo partecipante, richiesto per l'analisi statistica o il follow-up di safety, a seconda di quale evento accada per ultimo. |
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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 | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |