Panobinostat and Sorafenib in Treating Patients With Liver Cancer That is Metastatic and/or Cannot Be Removed by Surgery
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.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Combination of Sorafenib and LBH589 in Hepatocellular Carcinoma|
- Assessment of Safety and Tolerability [ Time Frame: 6months to 1 year ] [ Designated as safety issue: Yes ]•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.
- Progression-free survival [ Time Frame: 6mo 1 year ] [ Designated as safety issue: No ]Evaluate time to progression vs progression free survival
- Overall survival [ Time Frame: until death ] [ Designated as safety issue: No ]Overall survival (OS) will be measured from study entry until death from any cause.
- Response as assessed by RECIST [ Time Frame: every 42 days ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||March 2009|
|Study Completion Date:||June 2010|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Active Comparator: LBH589
This study utilizes a sequential dose-escalation design to define the MTD of LBH589 when combined with standard doses of sorafenib.
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 cycleDrug: sorafenib tosylate
400 mg PO BID
- 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.
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Richard Kim, MD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|