Efficacy and Safety Doxorubicin Transdrug Study in Patients Suffering From Advanced Hepatocellular Carcinoma

Inclusion Criteria

• Male or non-pregnant, non-breast feeding female;
• Aged ≥ 18 years;
• Patient with:
• advanced HCC (BCLC-C according to BCLC staging classification) having progressed under Sorafenib therapy or intolerant to Sorafenib, or;
• intermediate HCC (BCLC-B) non eligible or non responders to transarterial chemoembolization (TACE), and having progressed under or intolerant to Sorafenib therapy
• Patients with porta hepatis lymph nodes, extrahepatic metastases, or portal/suprahepatic vein thrombosis without extension in inferior/superior vena cava, are eligible;
• HCC diagnosed according to the American Association for Study of Liver Diseases (AASLD) and/or European Association for the Study of the Liver (EASL) criteria:
• Radiological Criteria applicable in cirrhotic liver:
• Nodule ≥ 10 mm: one imaging technique among MRI and CT-scan showing typical appearances for HCC defined as arterial enhancement and rapid washout in portal venous or delayed phase;
• If appearance not typical for HCC on initial imaging: second contrast enhanced study (CT or MRI) showing typical appearances for HCC defined as arterial enhancement and rapid wash-out in portal venous or delayed phase;
• And/Or cyto-histology criteria (e.g. in case of atypical lesions for HCC at imaging, absence of cirrhosis);
• Without cirrhosis or with a non decompensated cirrhosis (Child-Pugh score from A5 to B7 included);
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
• Laboratory tests as follows:
• Platelets ≥ 50,000 /mm3
• Neutrophil count ≥ 1000/mm3
• Hemoglobin ≥ 10g/dL
• Serum transaminases grade 2;
• Presence of recent (< 6 months) or current cardiac failure (class III or IV New York Heart Association (NYHA) classification), recent (< 6 months) acute coronary syndrome, clinically significant ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke, myocardial infarction (MI)…);
• Prior cumulative dose of 300 mg/m² of doxorubicin or equivalent;
• Patients currently treated with immunosuppressive agents that cannot be stopped;
• Patients whose medical or surgical conditions are unstable and may not allow the study completion or compliance, and specially patients with uncontrolled diabetes;
• Uncontrolled systemic infection;
• Patients with a life expectancy of less than 2 months;
• Patients who have received an experimental drug in another clinical trial in the last 30 days prior to randomization in the present clinical trial;
• Women of child-bearing age who are unwilling or unable to use an effective contraception method during the study treatment period and for 6 months after the last administration of study drug, and their male partner(s) refusing to use a condom (if applicable);
• Men who are unwilling or unable to use a condom during the study treatment period and for 6 months after the last administration of study drug, and their female partner(s) refusing to use one of the appropriate effective contraception methods (if applicable);
• Patients unwilling or unable to comply with protocol requirements and scheduled visits.