Panobinostat and Sorafenib in Treating Patients With Liver Cancer That is Metastatic and/or Cannot Be Removed by Surgery

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatocellular carcinoma

  • Metastatic and/or unresectable disease
  • Child-Pugh score A or B

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Neutrophil count > 1500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if elevation due to disease involvement)
• Serum bilirubin ≤ 1.5 times ULN
• Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
• Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN)
• Serum potassium ≥ LLN
• Serum sodium ≥ LLN
• Serum albumin ≥ LLN or 3 g/dL
• LVEF ≥ LLN as demonstrated by baseline MUGA or ECHO
• TSH and free T4 within normal limits (thyroid hormone replacement therapy allowed)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception (one being a barrier method) during and for 3 months after completion of study treatment
• INR < 1.5 or PT/PTT within normal limits

• No impaired cardiac function including any 1 of the following:

  • QTc > 450 msec on screening ECG
  • Congenital long QT syndrome
  • History of sustained ventricular tachycardia
  • History of ventricular fibrillation or torsades de pointes

  • Bradycardia, defined as heart rate < 50 beats per minute

    • Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible
  • Myocardial infarction or unstable angina within the past 6 months
  • Congestive heart failure (NYHA class III-IV)
  • Right bundle branch block and left anterior hemiblock (bifascicular block)
• No uncontrolled hypertension
• No thrombolic or embolic events (e.g., cerebrovascular accident and transient ischemic attacks) within the past 6 months
• No pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within the past 4 weeks
• No other hemorrhage/bleeding event > CTCAE Grade 3 within the past 4 weeks
• No unresolved diarrhea > CTCAE grade 1
• No other concurrent severe and/or uncontrolled medical conditions
• No other primary malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
• No serious non-healing wound, ulcer, or bone fracture
• No evidence or history of bleeding diathesis or coagulopathy
• No significant traumatic injury within the past 4 weeks
• No known or suspected allergy to sorafenib tosylate or any other study drug
• No condition that would impair a patient's ability to swallow whole pills
• No malabsorption problem
• No known human immunodeficiency virus (HIV) or hepatitis C positivity (baseline testing for HIV and hepatitis C is not required)
• No significant history of non-compliance to medical regimens

PRIOR CONCURRENT THERAPY:

• No prior HDAC inhibitors, DAC inhibitors, HSP90 inhibitors, sorafenib tosylate, or valproic acid for the treatment of cancer
• More than 4 weeks since prior chemotherapy, investigational drugs, or major surgery and recovered
• More than 4 weeks since open biopsy
• More than 5 days since prior and no concurrent valproic acid for any medical condition
• No concurrent St. John's wort or rifampin
• No concurrent drugs with a risk of causing torsades de pointes
• No concurrent CYP3A4 inhibitors
• No concurrent radiotherapy
• No concurrent grapefruit, grapefruit juice, or Seville (sour) oranges
• No other concurrent investigational therapy
• No other concurrent anticancer agents
• Concurrent anticoagulation treatment with warfarin or heparin allowed