E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced hepatocarcinoma (HCC) |
|
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 |
First part (phase 2) To evaluate the number of patient free of local progression assessed at 3 months after randomization in the Doxorubicin-Transdrug® treated group
Second part (phase 3) To compare time to local progression according to EASL criteria between the two groups
|
|
E.2.2 | Secondary objectives of the trial |
First part (phase 2) To evaluate the number of patient free of local progression assessed at 3 months after randomization for control group To determine pharmacokinetic profile of Doxorubicin-Transdrug® All the following secondary end-points will be based on a comparison between the treated and the control groups: - objective response rates according to EASL criteria - objective response rate according to RECIST criteria - tolerance
Second part (phase 3) All the following secondary end-points will be based on a comparison between the treated and the control groups: - progression free survival - overall survival - objective response rates according to EASL criteria - objective response rate according to RECIST criteria - tolerance - quality of life |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 18 to 80 years; • Patients with hepatocellular carcinoma (HCC), diagnosed according to AASLD guidelines; • Multinodular HCC regardless of the number of lesions, but with extension < 50% of the liver parenchyma; • Child-Pugh stage A; • Left ventricular ejection fraction (LVEF) ≥ 50% as determine by echocardiograph; • Adequate pulmonary function as measured by : - a vital capacity (VC) > 70% of the theoretical - a total lung capacity > 70% of the theoretical - a carbon monoxide diffusing capacity (DLCO) > 70% of the theoretical and a DLCO/VA > 70% of the theoretical - a forced expiratory volume in first second (FEV1)/ VC > 60% - a SaO2 > 92% ; • Platelets ≥ 75 x 109 L; • Absolute neutrophil count ≥ 1,0 x 109 L; • AST and/or ALT ≤ 5 times upper limit of normal (NCI/CTC Grade 0, 1, 2); • Prothrombin activity > 60% and V factor > 60%; • ECOG score 0 - 2 ; • Patients who have signed and dated written informed consent; • Completed a period of at least 30 days since ending investigational device or drug trial; • Women of childbearing potential should have highly effective contraception method (hormonal contraception, implantable contraceptive, injectable contraceptive double-barrier method or intrauterine device) required over 3 months prior and throughout the entire duration of the study |
|
E.4 | Principal exclusion criteria |
• Troncular or supra-hepatic vein thrombosis; • Right and left lobar portal thrombosis; • Risk for variceal bleeding diagnosed on a gastro-duodenal fibroscopy performed at least one year before enrolment and characterized by: - Large esophageal varices or isolated cluster of varices in fundus of stomach - Red wale marks (longitudinal red streaks on varices) - Cherry-red spots (red, discrete, flat spots on varices) - Hematocystic spots (red, discrete, raised spots) - Diffuse erythema; • HCC developed on a transplanted liver; • Presence of extra-hepatic metastases; • Patients able to benefit from a hepatic transplantation, surgical resection, percutaneous ethanol injection or radiofrequency ablation; • Prior systemic chemotherapy, TACE, embolisation, radiation therapy for HCC regardless of the time elapsed before the enrolment; • Patient having undergone a 450mg/m² cumulated dose of doxorubicin; • Patients who has benefited from a surgical resection or percutaneous treatment in the month preceding the enrolment; • Patient currently being treated by an immunosuppressor agent that cannot be stopped; • Patient treated by an anticoagulant that cannot be stopped; • Patient with unstable and developing medical-surgical problems; • Presence of cardiac insufficiency, ongoing coronaropathy, arrhythmia or conduction disorders on the electrocardiogram; • Patient with a life expectancy of less than 3 months; • Pregnant or breast-feeding women; • Patients with a mental deficiency preventing proper understanding of trial protocol requirements; • Prior entry into this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
First part (phase 2): - The rate of Doxorubicin Transdrug®-treated patients free of local progression according to EASL criteria evaluated by spiral CT scan performed 3 months after randomization (M3).
Second part (phase 3): - Time to local progression defined as the period between randomization and spiral CT scan showing documented progression, as confirmed by the external radiologist according to follow-up of 12 months according to EASL criteria. |
|
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 | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Center’s usual treatment practice (including TACE) |
|
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 | 36 |
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 |
|
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
|
From the first day of treatment to the end of study visit, the study period will be 12 months |
|
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 | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |