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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00873002
Recruitment Status : Terminated (Dose Limiting Toxicity)
First Posted : April 1, 2009
Last Update Posted : March 20, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Brief Summary:

RATIONALE: Panobinostat and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of liver cancer by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with sorafenib in treating patients with liver cancer that is metastatic and/or cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Liver Cancer Drug: panobinostat Drug: sorafenib tosylate Phase 1

Detailed Description:



  • Assess the safety and tolerability of panobinostat when combined with standard doses of sorafenib tosylate in patients with metastatic and/or unresectable hepatocellular carcinoma.
  • Determine the maximum tolerated dose of panobinostat when combined with standard doses of sorafenib tosylate in these patients.


  • Determine the response rate.
  • Determine the progression-free survival.
  • Determine the overall survival rate.

OUTLINE: This is a dose escalation study of panobinostat.

Patients receive panobinostat IV on days 1 and 8 and oral sorafenib tosylate twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed for 30 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Combination of Sorafenib and LBH589 in Hepatocellular Carcinoma
Study Start Date : March 2009
Primary Completion Date : May 2010
Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: LBH589
This study utilizes a sequential dose-escalation design to define the MTD of LBH589 when combined with standard doses of sorafenib.
Drug: panobinostat
Dose escalation: 7.5 mg/m2 day 1 and day 8 of 21 days cycle 10 mg/m2 day 1 and day 8 of 21 days cycle 15 mg/m2 day 1 and day 8 of 21 days cycle 20 mg/m2 day 1 and day 8 of 21 days cycle 30 mg/m2 day 1 and day 8 of 21 days cycle
Drug: sorafenib tosylate
400 mg PO BID

Primary Outcome Measures :
  1. Assessment of Safety and Tolerability [ Time Frame: 6months to 1 year ]
    •Primary objective of the phase I trial will be to assess the safety and tolerability and to determine the maximum tolerated dose (MTD) of LBH 589 when combined with standard doses of sorafenib in the treatment of hepatocellular carcinoma.

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 6mo 1 year ]
    Evaluate time to progression vs progression free survival

  2. Overall survival [ Time Frame: until death ]
    Overall survival (OS) will be measured from study entry until death from any cause.

  3. Response as assessed by RECIST [ Time Frame: every 42 days ]
    To ensure comparability, baseline methods and on-study methods for response assessment must be performed using identical techniques. In addition, all subjects with evidence of objective tumor response (CR, PR or SD) should have the response confirmed with repeat assessments at least 21 days after the first documentation of response, resuming bimonthly (every 42 days) assessments thereafter. Objective tumor response will be assessed using the RECIST method.

  4. Adverse events and abnormal laboratory value severity as assessed by NCI CTCAE version 3.0 [ Time Frame: weekly during treatment to 30 days after treatment ]
    Events should be documented and recorded at each visit. Subjects should be followed for adverse events for 30 days after the last protocol related assessment, or until drug-related toxicities have resolved, whichever is later.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed hepatocellular carcinoma

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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00873002

United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Richard Kim, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Additional Information:
Responsible Party: Case Comprehensive Cancer Center Identifier: NCT00873002     History of Changes
Other Study ID Numbers: CASE6208
P30CA043703 ( U.S. NIH Grant/Contract )
CASE6208 ( Other Identifier: Case Comprehensive Cancer Center )
First Posted: April 1, 2009    Key Record Dates
Last Update Posted: March 20, 2012
Last Verified: March 2012

Keywords provided by Case Comprehensive Cancer Center:
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
recurrent adult primary liver cancer
localized unresectable adult primary liver cancer

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Histone Deacetylase Inhibitors