E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hepatocellular carcinoma patients undergoing transarterial chemoembolisation (TACE) |
|
MedDRA Classification |
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 safety of Sorafenib plus TACE in HCC Patients |
|
E.2.2 | Secondary objectives of the trial |
• to evaluate portal hypertension and systemic hemodynamics • to evaluate liver stiffness as measured by Fibroscan • to evaluate proteomic changes in surrounding tissue • to evaluate mechanisms of Sorafenib resistance in tumor tissue • to evaluate DNA methylation of tumor genes in serum as marker of treatment response • to detect early response to Sorafenib and its possible impact on overall treatment response • to evaluate other markers treatment resistance and treatment response
• Time to progression • Overall survival
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
4.1 Inclusion criteria -Patients with histologically confirmed HCC not suitable for OLT or resection (>3 nodules, >5 cm diameter, vascular invasion, clinically significant portal hypertension, other contraindications against OLT) -Child-Pugh Stage A or B -Liver disease of any etiology -Written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures -Patient must be able to comply with the protocol -Age ≥18 years -Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the Sorafenib. Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) -Haematology: Absolute neutrophil count (ANC) > 1 x 109/L Platelet count > 40 x 109/L Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time 40% -Biochemistry: Total bilirubin 5 mg/dL Serum creatinine < 3.0 mg/dL -Life expectancy of >3 months
|
|
E.4 | Principal exclusion criteria |
Exclusion criteria: -extrahepatic tumor spread -complete portal vein thrombosis (common trunk) -Child-Pugh-Stage C -Prior TACE or TAE -Other experimental therapies for HCC -Acute variceal bleeding within the last 2 weeks -Large oesophageal varices (>5 mm diameter) without prophylactic band ligation -Past or current history (within the last 2 years prior to randomisation) of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix -History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke within < 6 months), excluding hepatic encephalopathy -Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study -Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants for therapeutic purposes -Chronic, daily treatment with aspirin (>325mg/day) -Pregnancy (positive serum pregnancy test) or lactation -Uncontrolled hypertension -Serious, non-healing wound, ulcer, or bone fracture -Currently or recent (within the 30 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study -Clinically significant (i.e. active) cardiovascular disease for example cerebravascular accidents (≤ 6 months prior to study entry), myocardial infarction (≤ 6 months prior to study entry), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication -Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of Sorafenib/TACE or patient at high risk from treatment complications
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety of Sorafenib plus TACE 12 weeks after the last 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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
TACE only group of an other randomized Phase2 TACE trial |
|
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |