E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hepatocellular carcinoma |
carcinoma epatocellulare (HCC) |
|
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 | SOC |
E.1.2 | Classification code | 10019805 |
E.1.2 | Term | Hepatobiliary disorders |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
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 evaluate the efficacy and safety of sorafenib versus placebo in the adjuvant treatment of patients with hepatocellular carcinoma (HCC) after treatments with TACE. |
Valutare l’efficacia e la sicurezza di sorafenib rispetto a placebo nel trattamento adiuvante di pazienti affetti da carcinoma epatocellulare (HCC) dopo trattamenti a base di TACE. |
|
E.2.2 | Secondary objectives of the trial |
overall survival
the disease-free survival
the number of patients without disease at 2 years
the percentage of patients who develop extrahepatic spread or macroscopic vascular invasion |
Valutare:
la sopravvivenza globale
la sopravvivenza libera da malattia
il numero di pazienti senza malattia a 2 anni
la percentuale di pazienti che sviluppano una diffusione extra-epatica od un’invasione vascolare macroscopica. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histological or cytological confirmation of HCC or meet the AASLD criteria for diagnosis of HCC
Radiological CR (as per mRECIST,Lencioni R. & Llovet M. 2010) after TACE +/- RFA or PEI procedures. Assessment of radiological CR after TACE that employed Lipiodol, will be done by MRI only |
Il paziente deve aver avuto una conferma istologica o citologica di HCC o deve soddisfare i criteri dell’AASLD per la diagnosi di HCC
Risposta radiologica completa (in base alle definizioni degli emendamenti della JNCI) dopo TACE +/- RFA o procedure di PEI. La valutazione della RC radiologica dopo TACE che ha impiegato Lipiodol verra' effettuata solo mediante la RMN |
|
E.4 | Principal exclusion criteria |
1. Patients that are candidates for radical (potentially curative) treatments including patients waiting for liver transplant
2. Presence of macroscopic vascular invasion (including segmental portal obstruction) or extrahepatic spread
3. Ascites refractory to diuretics
4. Subject undergoing renal dialysis
5. Active clinically serious infection (> grade 2 NCI-CTC version 4.0)
6. Prior systemic therapy for HCC with TKIs or agents acting on VEGFR
7. Investigational therapy within 4 weeks of trial entry
8. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
9. Thrombotic or embolic events (cerebrovascular accident including transient ischemic attacks, deep vein thrombosis or pulmonary embolism) within 6 months prior to randomization |
1. I pazienti candidati a trattamenti radicali (potenzialmente curativi) compresi i pazienti in attesa di un trapianto di fegato.
2. Presenza di invasione vascolare macroscopica (compresa l’ostruzione portale segmentale) o di diffusione extra-epatica
3. Ascite refrattaria ai diuretici
4. Soggetti sottoposti a dialisi renale
5. Infezione attiva clinicamente seria (> grado 2 NCI-CTC versione 4.0)
6. Precedente terapia sistemica del HCC con TKI o farmaci anti VEGFR
7. Partecipazione ad una terapia sperimentale entro 4 settimane dall’inclusione nello studio
8. Pazienti con emorragia gastrointestinale clinicamente significativa entro 30 giorni prima dell’inclusione nello studio
9. Eventi trombotici od embolici (accidenti cerebrovascolari compresi gli attacchi ischemici transitori, la trombosi venosa profonda o l’embolia polmonare) entro 6 mesi prima della randomizzazione |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy and safety of sorafenib versus placebo in the adjuvant treatment of patients with hepatocellular carcinoma (HCC) after treatments with TACE. |
Valutare l’efficacia e la sicurezza di sorafenib rispetto a placebo nel trattamento adiuvante di pazienti affetti da carcinoma epatocellulare (HCC) dopo trattamenti a base di TACE. |
|
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) | 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 | 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 | 25 |
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
| |
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 | 36 |
E.8.9.1 | In the Member State concerned days | 0 |