E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Squamous Non-Small-Cell Lung Cancer (NSCLC) |
Advanced or Metastatic Squamous Non-Small-Cell Lung Cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Advanced or Metastatic Squamous Non-Small-Cell Lung Cancer (NSCLC) |
Advanced or Metastatic Squamous Non-Small-Cell Lung Cancer (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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025044 |
E.1.2 | Term | Lung cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objective of the study is to assess whether the addition of oral veliparib to carboplatin and paclitaxel will improve overall survival (OS) when compared to the addition of placebo to carboplatin and paclitaxel, in subjects with previously untreated locally advanced and metastatic squamous NSCLC |
L’obiettivo primario della sperimentazione è di verificare se l’aggiunta di veliparib orale a carboplatino e paclitaxel sia in grado di migliorare la sopravvivenza globale (OS) rispetto all’aggiunta di placebo a carboplatino e paclitaxel, in soggetti con NSCLC squamocellulare avanzato o metastatico che non hanno mai ricevuto in precedenza un trattamento per tale patologia |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess the effects of veliparib combination therapy on: duration of overall response (DOR), progression-free survival (PFS), and objective response rate (ORR). |
Gli obiettivi secondari della sperimentazione sono di valutare gli effetti della terapia combinata di veliparib su: durata della risposta globale (DOR), la sopravvivenza libera da progressione (PFS) e il tasso di risposta oggettiva (ORR) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic substudy - optional blood test |
Sottostudio di Farmacogenetica – campione di sangue opzionale |
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E.3 | Principal inclusion criteria |
-Subject must be ≥ 18 years of age.
-Life expectancy > 12 weeks
-Subject must have cytologically or histologically confirmed squamous NSCLC.
-Subject must have advanced or metastatic squamous NSCLC (stage IIIB or IV) that is not amenable to surgical resection or radiation with curative intent at time of study Screening. Subjects with recurrent squamous NSCLC after surgical treatment that is not amenable to surgical resection or radiation with curative intent are eligible.
-Subject must have at least 1 unidimensional measurable NSCLC lesion on a CT scan as defined by RECIST (version 1.1). |
-Soggetto di età ≥ 18 anni.
-Aspettativa di vita > 12 settimane
- Soggetto affetto da NSCLC squamocellulare confermato da citologia o istologia.
- Soggetto affetto da NSCLC squamocellulare avanzato o metastatico (stadio IIIB o IV) non trattabile con la resezione chirurgica o radioterapia curativa al momento dello Screening previsto dalla sperimentazione. I soggetti con NSCLC squamocellulare recidivante dopo trattamento chirurgico che non è possibile sottoporre a resezione chirurgica o radioterapia con intento curativo sono idonei all’arruolamento.
-Soggetto con almeno una lesione da NSCLC misurabile in una dimensione rilevata da scansione TAC secondo i criteri RECIST (versione 1.1)
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E.4 | Principal exclusion criteria |
-Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).
-Subject has a known hypersensitivity to platinum compounds. Subject has peripheral neuropathy ≥ grade 2.
-Subject has non-squamous NSCLC, or a known EGFR mutation of exon 19 deletion or L858R mutation in exon 21, or a known ALK gene rearrangement.
-Subject has received prior systemic anti-cancer therapy for advanced or metastatic NSCLC. |
- Soggetto con nota ipersensibilità al paclitaxel o ad altri farmaci la cui formulazione contiene olio di ricino poliossietilato (Cremophor).
- Soggetto con nota ipersensibilità a composti a base di platino.
- Soggetto con neuropatia periferica di grado ≥ 2.
-Soggetto affetto da NSCLC non squamocellulare, oppure presenza di una mutazione nota nel gene EGFR come delezione dell’esone 19 oppure mutazione L858R dell’esone 21, oppure riarrangiamento noto del gene ALK.
-Soggetto che ha ricevuto una pregressa terapia anti-neoplastica sistemica per NSCLC avanzato o metastatico
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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 |
Time to death for a given subject will be defined as the number of days from the date that the subject was randomized to the date of the subject's death. |
Il tempo di sopravvivenza per un determinato soggetto sarà definita come il numero dei giorni dalla data in cui il soggetto è stato randomizzato alla data della morte del soggetto |
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E.5.2 | Secondary end point(s) |
Duration of Response (DOR); Progression-free Survival (PFS); Objective Response Rate (ORR). |
Durata della Risposta Globale (DOR); Sopravvivenza libera da Progressione (PFS); Tasso di Risposta Oggettiva (ORR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The duration of overall response will be defined as the number of days from CR or PR to PD. PFS will be defined as the number of days from the date of randomization to the date of disease progression or death if disease progression is not reached. Objective response rate is defined as the proportion of subjects with complete or partial response as determined by the investigator per RECIST (version 1.1). |
La durata della risposta globale sarà definita come il numero dei giorni dalla CR oppure PR alla PD. Il PFS sarà definito come il numero dei giorni dalla data di randomizzazione alla data della progressione della malattia o della morte se la progressione della malattia non è raggiunta. Il tasso di risposta oggettiva è definito come la proporzione di soggetti con risposta completa o parziale come determinata dallo sperimentatore secondo i criteri RECIST (versione 1.1) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life, Performance Status (ECOG) |
Qualità di vita e Performance Status (ECOG) |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
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 |
Australia |
Austria |
Belarus |
Brazil |
Canada |
Croatia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Latvia |
Lithuania |
Mexico |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Russian Federation |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Turkey |
Ukraine |
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
|
The end-of-study is defined as the date of last subject's last visit. The sponsor may also end the study upon confirmation that the primary endpoint was statistically met. |
La fine dello studio è definita come la data dell’ultima visita dell’ultimo soggetto. Lo sponsor potrebbe anche terminare lo studio dopo la conferma che il criterio di endpoint primario è stato statisticamente raggiunto |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |