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