hepatocellular carcinoma MedDRA version: 12.1 Level: LLT Classification code 10019830 Term: Hepatocellular carcinoma resectable MedDRA version: 12.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable MedDRA version: 12.1 Level: LLT Classification code 10019829 Term: He
Conditions
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient with histologically or cytologically confirmed advanced-stage hepatocellular carcinoma (HCC) (unresectable, and/or metastatic) or responding to the Barcelona diagnostic criteria 2. Patient who have discontinued from first line treatment with sorafenib monotherapy for any reason (ie, tumor disease progression, intolerance) at least 14 days prior to planned randomization but have not received any second line treatment for HCC 3. Patient who have recovered from any significant sorafenib-related treatment toxicities prior to randomization (=Grade 2) 4. Patient with at least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST) 5. Patients who have received local therapy prior to sorafenib administration (radiation, surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection [PEI] or cryoablation) are eligible. Local therapy must be completed at least 4 weeks prior to the baseline scan 6. Adequate antiviral systemic therapy in sympotomatic and asymptomatic HBV Ag carriers 7. Patient eligible for receiving a second line treatment including etoposide and irinotecan 8. Child-Pugh liver function class A 9. Barcelona Clinic Liver Cancer (BCLC) classification: class C 10. Eastern Cooperative Oncology Group (ECOG) Performance Status = 2 11. Patient with adequate organ function: • Absolute Neutrophil Count (ANC) = 1.5 x 109/L • Haemoglobin = 10 g/dL • Platelets (PTL) = 85 x 109/L • AST/ALT = 5 x ULN • Gamma-GT = 5 x ULN • Bilirubin = 1.5 x ULN • Creatinin clearance = 50 mL/min (Cockcroft and Gault formula) • Albumin > LLN • Urea = 2 x ULN • Proteinuria 40 kg and BMI > 18 15. Female patient of child bearing potential who agrees to use a method of medically acceptable forms of contraception during the study and 3 months after the last intake of study treatment 16. Patient able and willing to comply with study visits and procedures as per protocol 17. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed 18. Patient affiliated to a social security regimen Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patient intolerant to etoposide or irinotecan 2. Patient who have received a liver transplant 3. Patient with clinically significant symptoms of hepatic encephalopathy 4. Patient who have received a previous systemic therapy (including investigational agents) other than sorafenib (see Inclusion Criterion 2) for treatment of HCC. Patients participating in surveys or observational studies are eligible to participate in this study 5. Patient who have had treatment with any of the following within the specified timeframe prior to randomization: • Any sorafenib within the 14 days prior to randomization • Major surgery within the 4 weeks prior to randomization • Any transfusion, treatment with blood component preparation, received erythropoietin , albumin preparation, and granulocyte colony-stimulating factor (G CSF) within the 2 weeks prior to randomization 6. Patient with previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted 7. Patient presenting with at least one of the following condition: - Ischemic heart disease, defined by at least one of the following condition: a. Medical history of ischemic heart disease b. Clinical symptoms of ischemic heart disease c. Q wave > 3 mm on the electrocardiogram d. ST elevation or depression > 2 mm on the electrocardiogram e. Negative T wave in at least 2 leads of the electrocardiogram - Cardiac failure, defined by at least one of the following condition: a. Medical history of cardiac failure defined by a previous left ventricular ejection fraction = 50% b. Clinical symptoms of cardiac failure c. Current treatment for cardiac failure d. NT Pro-BNP = 300 pg/mL or BNP = 75 pg/mL and/or troponin T > 0.1 ng/mL or troponin I > 0.35 ng/mL - Conduction disorders or arrhythmia, defined by at least one of the following and confirmed by electrocardiogram: a. Severe ventricular arrhythmia (frequent premature ventricular beats) b. Atrioventricular block at second or third level c. Left bundle branch block 8. Pregnant or nursing female patient 9. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis 10. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent. Previous treatment 11. Patient treated with any investigational agent within 4 weeks prior baseline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall Progression Free Survival (PFS); Secondary Objective: Survival - Overall survival (OS) - Survival rate at week 6, 12, 18, 24 - PFS rate at week 6, 12, 18, 24 Tumour assessment: - Overall Time to progression (TTP) - Objective response rate (CR + PR) at week 6, 12, 18, 24 - Control disease rate (CR + PR + SD) at week 6, 12, 18, 24 - Best response during study treatment - Time to response - Quality of life assessment according to the EORTC QLQ-C30 questionnaire at week 6, 12, 18, 24 - ECOG Performance Status Safety profile using the NCI CTC v4.02 classification Pharmacokinetics ;Primary end point(s): Progression Free Survival (PFS) is defined as the time from the randomization to the date of documented progression or any cause of death during the study. Progression will be assessed by CT scan according to Modified-RECIST criteria version 1.1. | — |
Countries
Czech Republic, France, Greece, Spain
Outcome results
None listed