Advanced hepatocellular carcinoma (HCC) stage C (or better) according to BCLC classification restricted to Child-Pugh class A/B (5-7 points).
Conditions
Sponsors
Ethik-Kommission der Medizinischen Fakultät der Martin-Luther-Universität Halle Wittenberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: Patients may be included in the study only if they meet all the following criteria: 1. Non-resectable locally advanced or metastasized HCC 2. Subjects must have at least one tumor lesion that meets the following criteria: - the lesion can be accurately measured in at least one dimension according to RECIST 1.1 3. Subjects who have received local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) are eligible, provided that they have a target lesion which shows progress of the disease despite treatment.. Local therapy must be completed at least 4 weeks prior to the baseline scan. 4. Confirmation of disease by histology 5. Liver function: Child Pugh stage A/B (5-7 points) only 6. Tumor stage: BCLC stage C (or better) 7. ECOG performance status 0-2 8. Life expectancy of at least 12 weeks 9. Age = 18 years 10. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening and within 4 weeks before start of treatment: - Hemoglobin = 9.0 g/dl - Absolute neutrophil count (ANC) =1.500/mm3 - Platelet count = 70.000/µl - Total bilirubin = 3 mg/dl - ALT and AST = 5 x upper limit of normal - Alkaline phosphatase =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Patients will be excluded from the study for any of the following reasons: 1. Patients eligible for resection or transplantation 2. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study. However cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1) or any cancer curatively treated > 3 years prior to entry is permitted 3. Serious myocardial dysfunction: defined as absolute left ventricular ejection fraction (LVEF) 160 mmHg or diastolic blood pressure > 90 mm Hg despite optimal treatment 8. Known history of HIV infection 9. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 10. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry) 11. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) 12. History of organ allograft 13. Patients with evidence or history of bleeding diathesis 14. Thrombotic or embolic events within the last 6 months 15. Serious non-healing wound, fracture, or ulcer 16. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial for at least 6 months after last administration of doxorubicin and 2 months after the last administration of sorafenib. 17. Severe concomitant disease or psychiatric disorders 18. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results 19. Known severe hypersensitivity to sorafenib, doxorubicin or any of the excipients 20. Patients unable to swallow oral medications 21. Incompliance / contraindications against study medication Excluded therapies and medications, previous and concomitant: 22. Previous systemic therapy for HCC 23. Anticancer chemotherapy or immunotherapy or targeted therapy (except study medication) during the study or within 4 weeks of study entry. 24. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study 25. Autologous bone marrow transplant or stem cell rescue within 4 months of study 26. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Time to progression (TTP) according to RECIST 1.1 criteria;Secondary Objective: • Assessment of overall survival (OS) • Assessment of disease control rate (CR, PR, SD) according to RECIST 1.1 criteria • Assessment of disease control rate (CR, PR, SD) according to EASL criteria • Assessment of safety • Assessment of quality of life (FACT-Hep) • Assessment of the potential of biomarkers (AFP, VEGF, PDGF serum/plasma; vascular invasion, markers of stem cells and multi-drug resistance in biopsies) to predict tumor response ;Primary end point(s): • Time to progression (TTP) according to RECIST 1.1 Creteria | — |
Countries
Germany
Outcome results
None listed