Sorafenib and LBH589 in Hepatocellular Carcinoma (HCC)

Inclusion Criteria: * male or female patients \> 18 years of age * patients who have a life expectancy of at least 12 weeks * patients with advanced hepatocellular carcinoma * patients with have histologically or radiologically confirmed HCC; documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable * at least one tumor lesion that can be accurately measured in at least one dimension according to RECIST and which has not been treated with local therapy (hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection); the scans should be approximately 2 weeks old to be used as baseline scan * patients who received Sorafenib 2 x 400 mg a day between 4 to 6 weeks without dose reduction due to dose limiting toxicities * at least a period of 4 weeks prior to baseline scan after completion of a local therapy such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation * patients who have an ECOG PS of 0, 1 or 2 respectively Karnofsky Performance Status \> 70% * cirrhotic status of Child-Pugh-class A or B (max. 7 points); Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period * no signs of decompensated liver cirrhosis * white blood cells \> 3,000/mm³ * neutrophils \> 1,500/mm³ * platelets \> 100,000/mm³ * bilirubin \> 3x upper limit of normal (ULN) * AST and ALT \> 3x ULN * creatinine normal * PTT \< 1.5x ULN * fasting serum cholesterol \< 350 mg/dL * triglycerides \< 300 mg/dL * proteinuria \< 1g in 24 h * no history of allergic reactions to compounds similar to Panobinostat or Sorafenib * no prior thromboembolic disease * no history of hematemesis or hemoptysis * no other uncontrolled illness * women of childbearing potential must have had a negative serum or urine pregnancy test 48 hours prior to the administration of the first study treatment * patients who give a written informed consent obtained according to local guidelines * no other concurrent investigational drugs or anticancer agents * no concurrent traditional Chinese or herbal medicine (e.g. sho-saiko-to, silymarine) Exclusion Criteria: * patients currently receiving chemotherapy, immunotherapy or radio-therapy or who have received these within 4 weeks of study entry * patients who do not tolerate therapy with Sorafenib 2 x 400 mg a day * prior use of systemic investigational agents for HCC * 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 and any cancer curatively treated \> 3 years prior to entry is permitted; * chronic treatment with steroids or another immunosuppressive agent * a known history of HIV seropositivity * renal failure requiring hemo- or peritoneal dialysis * history of cardiac disease: congestive heart failure (\> New York Heart Association class 2), active coronary artery disease, cardiac arrhythmias requiring anti- arrhythmic therapy other than beta blockers or digoxin, uncontrolled hypertension; myocardial infarction more than 6 month prior to study entry is permitted * active clinically serious infections (\> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events - CTCAE - version 3.0) * known carcinomatous meningitis or uncontrolled brain disease * patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry or on oral anti-vitamin K medication (except low dose coumarin) * history of organ allograft * uncontrolled diabetes * impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption LBH589 or Sorafenib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome) * patients who have not recovered from surgery * female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes * patients who are using other investigational agents or who had received investigational drugs \> 4 weeks prior to study inclusion * history of noncompliance to medical regimens * patients unwilling to or unable to comply with the protocol * substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results