E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced (Stage IIIB or IV) NSCLC previously treated withh 4 cycles of a platinum-based chemotherapy (for Tarceva(r)) |
NSCLC avanzato (stadio IIIB o IV) precedentemente trattato con 4 cicli di una chemioterapia a base di platino (per Tarceva (r)) |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Non-small Cell Lung Cancer. |
Cancro avanzato del polmone 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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
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 |
Outcome Measure: Overall survival (OS): First-line maintenance Tarceva versus Tarceva at a time of disease progression |
Risultato valutato: sopravvivenza globale (OS): Tarceva in mantenimento in prima linea rispetto a Tarceva alla progressione della malattia |
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E.2.2 | Secondary objectives of the trial |
- Outcome Measure: Progression-free survival (PFS): First-line maintenance Tarceva versus placebo (tumour assessments according to RECIST criteria) - Outcome Measure: Overall response rate (ORR): First-line maintenance Tarceva versus placebo) - Outcome Measure: Disease control rate (DCR): First-line maintenance Tarceva versus placebo - Outcome Measure: Safety: Incidence of adverse events |
- Risultato valutato: sopravvivenza libera da progressione (PFS): Tarceva in mantenimento in prima linea rispetto al placebo (valutazioni del tumore in base ai criteri RECIST) - Risultato valutato: tasso di risposta globale (ORR): Tarceva in mantenimento in prima linea rispetto al placebo) - Risultato valutato: tasso di controllo della malattia (DCR): Tarceva in mantenimento in prima linea rispetto al placebo - Risultato valutato: Sicurezza: incidenza di eventi avversi |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients, >/= 18 year of age (or >/= legal age of consent if greater than 18) - Advanced or recurrent (Stage IIIb) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) - Completion of 4 cycles of platinum-based chemotherapy without progression (end of last chemotherapy cycle </= 28 days prior to randomization) - ECOG performance status 0-1 |
- Pazienti adulti,>/= 18 anni di età (o >/= dell’età legale per consenso, se maggiore di 18) - Cancro al polmone non a piccole cellule (NSCLC) avanzato o ricorrente (stadio IIIb) o metastatico (stadio IV) - Aver completato 4 cicli di chemioterapia a base di platino senza progressione (la fine dell’ultimo ciclo di chemioterapia </= 28 giorni prima della randomizzazione) - Stato di performance ECOG 0-1 |
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E.4 | Principal exclusion criteria |
- Prior exposure to agents directed at HER axis (e.g. erlotinib, gafitinib, cetuximab) - Patients whose tumors harbour an EGFR activating mutation - Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease before screening (platinum-based chemotherapy) - Use of pemetrexed in maintenance setting (pemetrexed is allowed during the chemotherapy run-in) - Patients who have undergone complete tumour resection after responding to the platinum-based chemotherapy during the screening phase Any other malignancies within 5 years, except for curatively resected carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ or organ confined prostate cancer - CNS metastases or spinal cord compression that has not been definitely treated with surgery and/or radiation, or treated CNS metastases or spinal cord compression without stable disease for >/= 2 months - HIV, hepatitis B or hepatitis C infection - Any inflammatory changes of the surface of the eye |
- Precedente esposizione ad agenti diretti contro l'asse HER (e.g. erlotinib, gafitinib, cetuximab) - Pazienti il cui tumore presenta una mutazione attivante per EGFR - Precedente chemioterapia o terapia con agenti anti-neoplastici sistemici per patologia avanzata prima dello screening (chemioterapia a base di platino) - Uso di pemetrexed in regime di mantenimento (pemetrexed è permesso durante il run-in della chemioterapia) - I pazienti che hanno effettuato una resezione completa del tumore dopo aver risposto ad una chemioterapia a base di platino nel corso della fase di screening - Qualunque altro tumore nei 5 anni precedenti, fatta eccezione per resezioni terapeutiche del carcinoma della cervice in situ, cancro della pelle basale o squamoso, carcinoma duttale in situ o cancro della prostata confinato all'organo - Metastasi CNS o compressione della colonna vertebrale che non sono state trattate in modo definitivo con la chirurgia e/o radioterapia, o metastsi al CNS o compressioni della colonna vertebrale trattate senza patologia stabile per >/= 2 mesi - Infezione da HIV, epatite B o epatice C - Qualunque cambiamento della superficie dell'occhio di tipo infiammatorio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS): First-line maintenance Tarceva versus Tarceva at time of disease progression |
Sopravvivenza globale (OS): Tarceva in mantenimento in prima linea rispetto a Tarceva alla progressione della malattia |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timeframe: 42 months |
Tempo di rilevazione: 42 mesi |
|
E.5.2 | Secondary end point(s) |
- Outcome Measure: Progression-free survival (PFS): First-line maintenance Tarceva versus placebo (tumour assessments according to RECIST criteria) - Outcome Measure: Overall response rate (ORR): First-line maintenance Tarceva versus placebo) - Outcome Measure: Disease control rate (DCR): First-line maintenance Tarceva versus placebo - Outcome Measure: Safety: Incidence of adverse events |
- Risultato valutato: sopravvivenza libera da progressione (PFS): Tarceva in mantenimento in prima linea rispetto al placebo (valutazioni del tumore in base ai criteri RECIST) - Risultato valutato: tasso di risposta globale (ORR): Tarceva in mantenimento in prima linea rispetto al placebo) - Risultato valutato: tasso di controllo della malattia (DCR): Tarceva in mantenimento in prima linea rispetto al placebo - Risultato valutato: Sicurezza: incidenza di eventi avversi |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Progression-free survival (PFS): Timeframe: 42 months - Overall response rate (ORR): Timeframe: 42 months - Disease control rate (DCR): - Safety: Incidence of adverse events: Timeframe: 42 months |
- Sopravvivenza libera da progressione (PFS): Tempo di rilevazione: 42 mesi - Tasso di risposta globale (ORR): Tempo di rilevazione: 42 mesi - Tasso di controllo della malattia (DCR): - Sicurezza: Incidenza degli eventi avversi: Tempo di rilevazione: 42 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 | No |
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 | Yes |
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) | 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 | 12 |
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 | 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 |
Brazil |
Canada |
Chile |
China |
South Africa |
Taiwan |
Thailand |
Ukraine |
United States |
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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 study will end when the final analysis for the primary endpoint (Overall Survival) has been performed. This will occur when the required numbers of events (460 deaths) is achieved, which is expected to happen approximately 10 months after the last patient has been randomized. |
Lo studio terminerà con l'esecuzione dell'analisi finale per l'obiettivo primario (Overall Survival). Questo avverrà al raggiungimento del numero necessario di eventi (460 morti), atteso circa 10 mesi dopo che l'ultimo paziente è stato randomizzato. |
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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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |