E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patient in advanced pancreatic neuroendocrine tumors |
Pazienti adulti con con tumore neuroendocrino pancreatico in stadio avanzato |
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E.1.1.1 | Medical condition in easily understood language |
Adult patient with pancreatic neuroendocrine tumors |
Pazienti adulti con con tumore neuroendocrino pancreatico |
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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 | 10062476 |
E.1.2 | Term | Neuroendocrine tumor |
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 estimate the efficacy of BEZ235 in adult patients with advanced (unresectable or metastatic) pNET |
Stimare l'efficacia di BEZ235 in pazienti adulti con pNET in stadio avanzato (non resecabile o metastatico) |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of BEZ235 therapy To evaluate the efficacy of BEZ235 per modified RECIST v.1.1. |
Valutare la sicurezza e la tollerabilità della terapia con BEZ235. Valutare l'efficacia di BEZ235 in base ai criteri RECIST v.1.1 modificati. |
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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:
Vers:00
Date:2012/06/14
Title:Biomarker Research Studies
Objectives:Biomarker studies are done to evaluate changes in genes and proteins and are important to learn about the effect of the drug on the body and cancer.
PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:00
Date:2012/06/14
Title:Pharmacokinetic Research Study
Objectives:Pharmacokinetic study is done to evaluate the amount of BEZ235 compound in blood. 30 people who are taking part in the CBEZ235F2201 study will take part to pharmacokinetic evaluations.
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FARMACOGENETICA:
Vers:00
Data:2012/06/14
Titolo:Studio complementare sugli indicatori biologici
Obiettivi:Gli studi sugli indicatori biologici sono effettuati per valutare le modifiche nei geni e nelle proteine e sono importanti per comprendere l'effetto del farmaco sull'organismo e sul tumore.
FARMACOCINETICA/FARMACODINAMICA:
Vers:00
Data:2012/06/14
Titolo:Studio complementare di farmacocinetica
Obiettivi:La valutazione farmacocinetica viene condotta per valutare il quantitativo di BEZ235 nel sangue. Prenderanno parte alla valutazione farmacocinetica 30 pazienti che partecipano allo studio CBEZ235F2201.
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E.3 | Principal inclusion criteria |
1. Patient must have advanced (unresectable or metastatic), histologically confirmed low or intermediate grade pancreatic pNET according to the WHO 2010 classification (grade 1 or 2) and show radiological evidence of disease progression since last treatment. 2. Patients’ disease is refractory to treatment with mTOR inhibitor. Patients must not have taken another treatment between mTOR inhibitor and BEZ235. NOTE: Refractory is defined as progression while on treatment or within 3 months of treatment discontinuation. 3. Measurable disease per RECIST Version 1.1 using Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). 4. Prior or concurrent therapy with SSA is permitted; however, for concurrent therapy with SSA while on study, patients must be on a stable dose at least 2 months prior to study start and must continue on the stable dose while receiving study treatment. 5. Adequate bone marrow function or organ function. 6. WHO PS ≤ 1. 7. Adult male or female patients ≥ 18 years of age. |
1.Pazienti con pNET in stadio avanzato (non resecabile o metastatico), istologicamente confermato, di grado basso o intermedio in base alla classificazione WHO 2010 (grado 1 o 2) e che mostrano evidenza radiologica di progressione di malattia dall'ultimo trattamento. 2.Pazienti con malattia refrattaria al trattamento con inibitore di mTOR (progressione durante il trattamento o entro 3 mesi dall'interruzione del trattamento). I pazienti non devono aver assunto un altro trattamento tra l'inibitore di mTOR e BEZ235. 3.Malattia misurabile in base ai criteri RECIST versione 1.1. 4.É consentita la terapia pregressa o concomitante con SSA; i pazienti devono essere in trattamento con la stessa dose da almeno due mesi prima dell'inizio dello studio e devono mantenerere la stessa dose di trattamento durante la somministrazione del trattamento in studio. 5.Funzionalità del midollo osseo o funzionalità d'organo adeguata. 6.WHO PS ≤ 1. 7.Pazienti adulti di sesso maschile o femminile di età ≥ 18 anni. |
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E.4 | Principal exclusion criteria |
1. Patient has received previous treatment with any PI3K inhibitor or AKT inhibitor for the treatment of pNET. 2. Patient has discontinued prior mTOR inhibitor therapy due to toxicity. 3. Patient has poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma. 4. Patient has been treated with hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment. 5. Patients with more than 3 prior systemic treatment regimens. 6. Patient who has any severe and/or uncontrolled medical conditions. 7. Patient has any cardiac abnormalities. 8. Patient has impairment of GI function or GI disease that may significantly alter the absorption of study drug. |
1.Pazienti che hanno ricevuto in precedenza un trattamento con qualsiasi inibitore di PI3K o AKT per il trattamento del pNET. 2.Pazienti che hanno discontinuato la terapia precedente con inibitore di mTOR per tossicità. 3.Pazienti con carcinoma neuroendocrino scarsamente differenziato, carcinoma neuroendocrino ad alto grado, adenocarcinoide, 'goblet cell carcinoid' e carcinoma a piccole cellule. 4.Pazienti trattati con embolizzazione dell'arteria epatica nei 6 mesi precedenti (1 mese se ci sono altri siti di malattia misurabile), o crioablazione/ablazione con radiofrequenza delle metastasi epatiche nei 2 mesi precedenti l'arruolamento. 5.Pazienti trattati in precedenza con più di 3 regimi sistemici. 6.Pazienti con qualsiasi condizione medica severa e/o non controllata. 7.Pazienti con anomalie cardiache. 8.Pazienti con deterioramento della funzionalità gastrointestinale o patologia gastrointestinale che potrebbe alterare in modo significativo l'assorbimento del farmaco in studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS rate at 16 weeks according to local radiological assessment per modified RECIST v1.1 |
Tasso di PFS a 16 settimane in base alla valutazione radiologica locale secondo i criteri RECIST v.1.1 modificati. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to approx 18 months |
fino a circa 18 mesi |
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E.5.2 | Secondary end point(s) |
Frequency and severity of adverse events;other safety data as considered appropriate. Overall Response Rate, Disease Control Rate, Duration of Response. |
Frequenza e severità degli eventi avversi. Altri dati di sicurezza per quanto considerati appropriati. ORR, DCR, DoR (Overall Response Rate, Disease Control Rate, Duration of Response). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to approx. 18 months for all secondary endpoint |
fino a circa 18 mesi per tutti gli endpoint secondari |
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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 | 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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Korea, Republic of |
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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The end of study (last patient last visit) will occur after all patients have completed their last assessment as per protocol. The final analysis will be conducted after all enrolled patients have completed the study. |
La fine dello studio (LPLV) avverrà dopo che tutti i pazienti hanno completato l'ultima valutazione per protocollo. L'analisi finale verrà effettuata dopo che tutti i pazienti arruolati hanno completato lo studio. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 32 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 32 |
E.8.9.2 | In all countries concerned by the trial days | 0 |