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Phase I Study of Combination of Sorafenib and LBH589 in Hepatocellular Carcinoma

Phase 1
18 Years
Not Enrolling
Liver Cancer

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Trial Information

Phase I Study of Combination of Sorafenib and LBH589 in Hepatocellular Carcinoma



- Assess the safety and tolerability of panobinostat when combined with standard doses of
sorafenib tosylate in patients with metastatic and/or unresectable hepatocellular

- 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.

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Assessment of Safety and Tolerability

Outcome Description:

•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.

Outcome Time Frame:

6months to 1 year

Safety Issue:


Principal Investigator

Richard Kim, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2009

Completion Date:

June 2010

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • advanced adult primary liver cancer
  • recurrent adult primary liver cancer
  • localized unresectable adult primary liver cancer
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Cleveland, Ohio  44195