E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The aim of this study is to evaluate the activity of a maintenance therapy with everolimus 10 mg daily in patients with stable disease, partial response or complete response after 6 cycles of induction chemotherapy with cisplatin or carboplatin plus etoposide administered according to clinical practice. |
L'obiettivo dello studi è quello di valutare l'attività di everolimus come terapia di mantenimento con everolimus 10 mg al giorno in pazienti con malattia stabile, in risposta parziale o completa dopo 6 cicli di chemioterapia con cisplatino ed etoposide somministrata in accordo con la pratica clinica |
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E.1.1.1 | Medical condition in easily understood language |
patients with neuroendocrine carcinoma with ki 67 less then 55% |
valutare l’attività di Everolimus in termini di PFS nella terapia di mantenimento di pazienti con carcinoma neuroendocrino con ki 67 inferiore al 55%. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary endpoint is progression free survival (PFS) defined as the time between randomization and the first evidence of progressive disease or date of death, whichever occurs first. Documentation of disease progression will be defined as per RECIST 1.1 criteria based on investigator assessment. The censoring date for a patient who is known to be progression-free would be the date of the last tumor assessment.
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Obiettivo principale: valutare l’attività di Everolimus in termini di PFS nella terapia di mantenimento di pazienti con carcinoma neuroendocrino ad origine gastroentero¬¬ pancreatica o polmonare con ki 67 inferiore al 55% in stabilita di malattia, risposta parziale o completa dopo 6 cicli di trattamento chemioterapico di prima linea con Cisplatino e VP 16. |
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E.2.2 | Secondary objectives of the trial |
Overall survival (OS) defined as the time from randomization to death from any cause Safety profile: Safety of the treatment will be evaluated by serious and non serious adverse events (AEs). AEs will be graded according to the CTCAE v4.03 Evaluation of prognostic/predictive factors on tumoral tissue and blood samples of patients treated with maintenance Everolimus: |
Sopravvivenza globale (OS), profilo di sicurezza, ricerca di fattori prognostici e predittivi sul tessuto tumorale e sul sangue periferico |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may be included in the study if they meet all of the following criteria: • Histological / cytological diagnosis of GEP Neuroendocrine Carcinoma (NEC) with Ki67< 55% (WHO 2010) • Histological/cytological diagnosis of large-cells neuroendocrine carcinoma of the lung with Ki67 <55%; • Stable disease, partial response or complete response (Recist 1.1) after 6 cycles of first line chemotherapy with Cisplatin plus Etoposide • non functional NEC • locally advanced inoperable or metastatic disease • measurable or evaluable disease according to RECIST criteria (version 1.1) • Age> 18; • ECOG performance status ≤ 2; • Adequate bone marrow function (Hb> 9.0 g / dL, absolute neutrophil count> 1.5 x 109 / L, platelets> 100 x 109 / L), renal function (serum creatinine <2 mg / dL x ULN or creatinine clearance, Cockroft formula, ≥ 30 ml / min), hepatic function (serum bilirubin <1.5 x ULN, serum transaminases <2.5 x ULN in the absence of liver metastases or <5x ULN in the presence of liver metastases); • Negative pregnancy test or breastfeeding women during childbearing age; • Written informed consent; • Approval of the Ethics Committee that will be required.
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diagnosi istologica o citologica di GEP NEC con Ki67< 55% (WHO 2010) large-carcinoma neuroendocrino del polmone con Ki67 <55%; malattia stabile, in risposta parziale o complete (Recist 1.1) dopo 6 cicli di chemioterapia di prima linea con Cisplatino piu Etoposide, NEC non funzionante, malattia misurabile, età> 18; ECOG performance status ≤ 2; adeguata funzionalità d’organo.
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E.4 | Principal exclusion criteria |
• clinically significant cardiovascular disorders in the 6 months prior to randomization (congestive heart failure, myocardial infarction, unstable angina, severe uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular accidents, pulmonary thromboembolism); • Functional Neuroendocrine Carcinoma NEC • Neuroendocrine carcinoma with ki 67 > 55% • ongoing uncontrolled infection; • Concomitant intake of: - Drugs incompatible with concomitant everolimus; - Any other drug in clinical trials; • History of other malignancy except carcinoma in situ of the cervix or basal / squamous cell carcinoma of the skin adequately treated; • Presence of brain metastases; • Any other serious or uncontrolled concurrent disease conditions that the safe administration of medications
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disordini cardiovascolari clinicamente significativi nei 6 mesi precedenti la randomizzazione (insufficienca cardica congestizia, infarto del miocardio, angina instabile, aritmie cardiache non controllate, NEC funzionanti, ki 67 > 55%, infezioni non controllate in atto. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) |
Progression free survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Overall survival (OS), safety profile, evaluation of prognostic/predictive factors on tumoral tissue and blood samples
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Sopravvivenza globale (OS), profilo di sicurezza, ricerca di fattori prognostici e predittivi sul tessuto tumorale e sul sangue periferico |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
10 months for OS and during maintenace treatment for safety profile and evaluation of prognostic/predictive factors on tumoral tissue and blood samples |
10 mesi per la sopravvivenza globale e durante la terapia di mantenimento per profilo di sicurezza, ricerca di fattori prognostici e predittivi sul tessuto tumorale e sul sangue periferico |
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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 | 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) | 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 | 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 | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 the trials is extimated after 36 months from the first patient randomized |
La fine dello studio è stimata circa 36 mesi dopo la randomizzazione del primo 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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |