E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) |
Tumore al Polmone non a Piccole Cellule ( NSCLC) ad istotipo squamoso in stadio Localmente avanzato o Metastatico |
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E.1.1.1 | Medical condition in easily understood language |
Lung Cancer |
Tumore al Polmone |
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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 | 10061873 |
E.1.2 | Term | 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 |
The primary objective of this study is to evaluate the ORR (CR + PR) associated with gemcitabine-carboplatin plus necitumumab in patients with locally advanced or metastatic EGFR expressing squamous NSCLC who have not received prior chemotherapy for this condition. |
L'obbiettivo primario di questo studio è valutare il tasso di risposta obiettiva (ORR) (risposta completa [CR] + risposta parziale [PR]) associato a gemcitabina-carboplatino più necitumumab in pazienti con NSCLC squamoso esprimente EGFR in stadio avanzato o metastatico che non hanno ricevuto una chemioterapia precedente per questa condizione.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• to evaluate OS, PFS, and DCR;
• to evaluate the safety profile of necitumumab in combination with gemcitabine-carboplatin chemotherapy;
• to characterize the PK of necitumumab.
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Gli obbiettivi secondari del presente studio sono: • valutare OS, PFS e DCR; • valutare il profilo di sicurezza di necitumumab associato a chemioterapia a base di gemcitabina-carboplatino; • caratterizzare la PK di necitumumab.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Have confirmed diagnosis of locally advanced or metastatic NSCLC predominantly squamous histology. Squamous NSCLC diagnosis must be
confirmed by histology or cytology local pathology report.
- Has an EGFR protein expressing tumor (defined by local IHC test).
- Measurable disease at the time of study entry as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- Has tumor tissue available for biomarker analyses.
- Has resolution of all clinically significant toxic effects of prior adjuvant and/or neoadjuvant chemotherapy, surgery, radiotherapy (with the exception of alopecia) to Grade =1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.
- Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1
- Have discontinued all previous treatments for cancer and recovered from the acute effects of therapy (Biologic agents (for example, antibodies) and Immunotherapy >=4 weeks; Chest radiotherapy >= weeks; Major surgery, excluding biopsy >=4 weeks)
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- Diagnosi confermata di NSCLC localmente avanzato o metastatico con istologia prevalentemente squamosa. La diagnosi di NSCLC squamoso deve essere confermata da un referto patologico istologico o citologico locale. - Presenza di un tumore esprimente la proteina EGFR (definito in base a un'analisi immunoistochimica locale). - Malattia misurabile al momento dell'ingresso nello studio definita in base ai Criteri di valutazione della risposta nei tumori solidi versione 1.1 (RECIST 1.1) - Disponibilità di tessuto tumorale per le analisi dei biomarcatori. - Risoluzione di tutti gli effetti tossici clinicamente significativi di precedente terapia adiuvante e/o chemioterapia neoadiuvante, intervento chirurgico, radioterapia (ad eccezione dell'alopecia) al grado =1 secondo i Criteri comuni della terminologia per gli eventi avversi del National Cancer Institute (NCI-CTCAE), versione 4.0. - Punteggio del performance status dell’Eastern Cooperative Oncology Group (PS ECOG) di 0-1 - Avere interrotto tutti i trattamenti antitumorali precedenti ed essersi ripresi dagli effetti acuti della terapia (agenti biologici (ad esempio anticorpi) e immunoterapia >=4 settimane; radioterapia toracica >= settimane; intervento chirurgico importante >=4 settimane)
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E.4 | Principal exclusion criteria |
- Has nonsquamous NSCLC
- Has received prior anticancer therapy targeting the EGFR, vascular
endothelial growth factor (VEGF), or VEGF receptor
- Has received previous chemotherapy (including concurrent
chemoradiation) for advanced NSCLC (patients who have received adjuvant
and/or neoadjuvant chemotherapy are eligible if the last administration
occurred at least 1 year prior to start of therapy).
- Has undergone major surgery or received any investigational
therapy in the 4 weeks prior to study enrollment.
- Has undergone chest irradiation within 4 weeks prior to study
enrollment (except palliative irradiation of bone lesions, which is allowed).
- Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants.
- Has a bleeding tumor
- History of arterial or venous thromboembolism within 3 months prior to study enrollment.
- Has a history or evidence of current clinically-relevant coronary artery disease of current = Class III as defined by Canadian Cardiovascular Society Angina Grading Scale (Campeau 1976) or congestive heart failure of current = Class III as defined by the New York Heart Association.
- Has experienced myocardial infarction within 6 months prior to study enrollment. |
- Avere NSCLC ad istotipo non squamoso - Avere ricevuto una precedente terapia antitumorale mirata contro EGFR, al fattore di crescita endoteliale vascolare (VEGF) o al recettore di VEGF - Avere ricevuto una precedente chemioterapia (compresa chemioradioterapia concomitante) per il NSCLC in stadio avanzato (i pazienti che hanno ricevuto una chemioterapia adiuvante e/o neoadiuvante sono idonei purché l'ultima somministrazione sia avvenuta almeno 1 anno prima dell'avvio della terapia). -Aver avuto Intervento chirurgico importante o una terapia sperimentale nelle 4 settimane precedenti all’arruolamento nello studio. - Irradiazione toracica nelle 4 settimane precedenti all’arruolamento nelllo studio (tranne nel caso di irradiazione palliativa di lesioni ossee, che è consentita). - Presenza di metastasi cerebrali sintomatiche o che richiedono un trattamento continuativo con steroidi o anticonvulsivanti. - Presenza di un tumore sanguinante - Anamnesi di tromboembolismo arterioso o venoso nei 3 mesi precedenti all'arruolamentoallo studio. - Anamnesi o evidenza di coronaropatia attuale clinicamente rilevante attualmente = Classe III secondo la definizione della Scala di classificazione dell'angina della Canadian Cardiovascular Society (Campeau 1976) o di insufficienza cardiaca congestizia attualmente = Classe III secondo la definizione della New York Heart Association. - Infarto miocardico nei 6 mesi precedenti all'arruolamento allo studio.
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR (CR + PR) based on tumor assessment using RECIST 1.1 |
ORR (CR + PR) in base alla valutazione del tumore secondo i criteri RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 6 months after enrolment completion. |
Circa 6 mesi dopo il termine dell'arruolamento |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints will include: . OS . PFS . DCR (CR, PR, and SD) based on tumor assessment using RECIST 1.1 The safety endpoints evaluated will include but are not limited to the following: . TEAEs, AEs, SAEs, and hospitalizations . Clinical laboratory tests, ECGs, vital signs, and physical examinations Assess PK parameters for necitumumab |
Gli endpoints di efficacia secondari includeranno: . OS . PFS . DCR (CR, PR e SD) in base alla valutazione del tumore secondo i criteri RECIST 1.1 Gli endpoints di sicurezza valutati comprenderanno, tra gli altri: . TEAEs, EAAEs, EAG SAEs e ricoveri ospedalieri . Analisi cliniche di laboratorio, ECG, parametri vitali ed esami obbiettivi Valutare i parametri di PK per necitumumab
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety: An interim safety analysis will be performed when at least 15 pts have completed at least 2 cycles (or otherwise discontinued study treatment). |
Sicurezza: Un'analisi ad interim della sicurezza verrà eseguita quando almeno 15 pazienti avranno completato almeno 2 cicli (o altrimenti interrotto il trattamento 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 | 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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Russian Federation |
Turkey |
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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
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The end of study occurs after study completion and when the last patient has discontinued study treatment and completed any applicable continued access follow-up procedures (last patient last visit). |
La fine dello studio avviene dopo il completamento dello studio e quando l'ultimo paziente ha interrotto il trattamento dello studio e ha terminato tutte le eventuali procedure di follow-up di accesso esteso (ultima visita dell'ultimo paziente).
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 15 |