E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally recurrent or metastatic non-squamous NSCLC which has progressed beyond 1st-line treatment with bevacizumab plus a platinum doublet-containing chemotherapy regimen and bevacizumab (monotherapy) maintenance treatment. |
NSCLC non-squamoso, localmente recidivante o metastatico, progredito dopo il trattamento di 1° linea con bevacizumab più un regime di chemioterapia contenente una doppietta a base di platino e il trattamento di mantenimento con bevacizumab (monoterapia). |
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E.1.1.1 | Medical condition in easily understood language |
Non-squamous non-small cell lung cancer (NSCLC) that has recurred or metastasized (spread from its original location to other parts of the body). |
Carcinoma polmonare non a piccole cellule, abbreviato in “NSCLC”, non-squamoso, in ricaduta o metastatico (che si è diffuso dalla sua localizzazione originaria ad altre parti del corpo). |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of 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 continuous bevacizumab treatment beyond PD1 as measured by overall survival (OS). |
Valutare l'efficacia del trattamento continuativo con bevacizumab dopo la prima progressione della malattia (PD1), misurata in base alla sopravvivenza globale (overall survival, OS). |
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E.2.2 | Secondary objectives of the trial |
- To assess the efficacy as measured by rate of 6-, 12-, and 18-month OS as measured from randomization at 1st progression of disease (PD1). - To assess the efficacy as measured by progression free survival (PFS) and time to progression (TTP) from randomization at PD1, to second (2nd) PD (PD2) (PFS2, TTP2), and to third (3rd) PD (PD3) - To assess the efficacy as measured by response rates (RRs), disease control rates, and duration of response at PD2 and PD3. - To assess the efficacy in the subgroup of adenocarcinoma patients. - To assess the safety of bevacizumab treatment across multiple lines of treatment. |
- Valutazione dell'efficacia, misurata in base al tasso di OS a 6, 12 e 18 mesi, dalla randomizzazione alla prima progressione della malattia (PD1). - Valutazione dell'efficacia, misurata in base alla sopravvivenza libera da progressione (progression free survival, PFS) e al tempo alla progressione (time to progression, TTP), dalla randomizzazione alla PD1, alla seconda (2°) PD (PD2) (PFS2, TTP2) e alla terza (3°) PD (PD3). - Valutazione dell'efficacia, misurata in base ai tassi di risposta (response rate, RR), ai tassi di controllo della malattia e alla persistenza della risposta, al momento della PD2 e della PD3 - Valutazione dell'efficacia nel sottogruppo di pazienti con adenocarcinoma - Valutazione della sicurezza del trattamento con bevacizumab in linee multiple di trattamento |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients, age >/=18 years - Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) - Documented progression of disease (locally recurrent or metastatic) per investigator assessment following firstline treatment 4-6 cycles of Avastin plus a platinum doublet-containing chemotherapy regimen and a minimum of 2 cycles of Avastin (monotherapy) maintenance treatment prior to first progression of disease - No treatment interruption of Avastin treatment greater than 2 consecutive cycles (42 days) between the start of first-line treatment to start of Cycle 1 of second line treatment - Randomization within 4 weeks of progression of disease - At least one unidimensionally measurable lesion meeting RECIST criteria - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 |
- Pazienti adulti, età >/= 18 anni - Canco al polmone non a piccole cellule(NSCLC) non-squamoso confermato istologicamente o citologicamente - Progressione della ptologia documentata (ricorrente locale o metastatica) secondo valutazione dello sperimentatore seguta da una prima linea di trattamento di 4-6 cicli di Avastin più una chemioterapia contenente una doppietta a base di platino ed un minimo di 2 cicli di Avastin (monoterapia) come trattamento di mantenimento prima della prima progressione di malattia - Nessuna interruzione nel trattamento con Avastin maggiore di 2 cicli consecutivi (42 giorni) tra l'inizio del trattamento in prima linea all'inizio del Ciclo 1 del trattamento in seconda linea - Randomizzazione entro 4 settimane dalla progressione della malattia - Almeno una lesione misurabile su una dimensione in accordo con i criteri RECIST - Stato di performance Eastern Cooperative Oncology Group (ECOG) di 0-2 |
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E.4 | Principal exclusion criteria |
- Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component - History of hemoptysis >/=grade 2 within 3 months of randomization - Major cardiac disease |
- Tumori misti non a piccole cellule e a piccole cellule o carcinomi adenosquamosi misti con una componente squamosa predominante - Storia di emottisi di grado >/= 2 entro tre mesi dalla randomizzazione - Patologie cardiache maggiori |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival |
Sopravvivenza globale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study end |
Fine dello studio |
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E.5.2 | Secondary end point(s) |
- Progression free survival - Time to progression - Response rates - Disease control rate - Duration of response in 2nd-line or 3rd-line |
- Sopravvivenza libera da malattia - Tempo alla progressione - Tassi di risposta - Tassi di controllo della malattia - Durata della risposta in 2 linea o in 3 linea |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study end |
Fine dello studio |
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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 | No |
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 |
Quality of life |
Qualita' della vita |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Bevacizumab+SOC vs SOC |
Bevacizumab+SOC vs SOC |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
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 | No |
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 |
Argentina |
Brazil |
India |
Japan |
Jordan |
Kuwait |
Lebanon |
Mexico |
Oman |
Qatar |
United Arab Emirates |
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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End of trial is defined as the completion of observation period (i.e. when 519 deaths have beenreported, which is expected to occur approximately 12 months after the last patient was randomized), or the date at which the last patient dies, whichever occurs first. |
La fine dello studio e' fissata al completamento del periodo di osservazione (quando saranno stati riportati 519 decessi, attesi dopo circa 12 mesi dalla randomizzazione dell'ultimo paziente) o alla data dell'ultimo decesso, quale si verifichi 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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |