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

NCT ID: NCT00873002

Last Updated: 2012-03-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-06-30

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.

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Conditions

Liver Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LBH589

This study utilizes a sequential dose-escalation design to define the MTD of LBH589 when combined with standard doses of sorafenib.

Group Type: ACTIVE_COMPARATOR

panobinostat

Intervention Type: DRUG

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

sorafenib tosylate

Intervention Type: DRUG

400 mg PO BID

Interventions

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

Intervention Type: DRUG

sorafenib tosylate

400 mg PO BID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Related Links

http://clinicaltrials.gov/ct2/show/NCT00873002?term=case6208&rank=1

Clinical trial summary from the National Cancer Institute's PDQ® database

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE6208

Identifier Type: OTHER

Identifier Source: secondary_id

CLBH589BUS23T

Identifier Type: -

Identifier Source: secondary_id

CASE6208

Identifier Type: -

Identifier Source: org_study_id