Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors
RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with epirubicin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with epirubicin in treating patients with metastatic malignant solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: epirubicin hydrochloride
Genetic: gene expression analysis
Genetic: protein expression analysis
Genetic: western blotting
Other: immunologic technique
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Panobinostat (LBH589) and Epirubicin in Patients With Solid Tumor Malignancies|
- Response as assessed by RECIST criteria [ Time Frame: 30 post end of study drug estimated to be ~24 weeks ] [ Designated as safety issue: No ]
- Progression as assessed by RECIST criteria [ Time Frame: 30 post end of study drug estimated to be ~24 weeks ] [ Designated as safety issue: No ]
- Adverse events and other symptoms as assessed by NCI CTCAE v3.0 [ Time Frame: 30 post end of study drug estimated to be ~24 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2009|
|Estimated Study Completion Date:||December 2014|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Experimental: treatment with Panobinostat and Epirubicin||Drug: epirubicin hydrochloride Drug: panobinostat Genetic: gene expression analysis Genetic: protein expression analysis Genetic: western blotting Other: immunologic technique Other: laboratory biomarker analysis Other: pharmacological study|
- To determine the safety, tolerability, maximum tolerated dose (MTD), and recommended phase II dose of panobinostat when administered with epirubicin hydrochloride in patients with metastatic malignant solid tumors.
- To determine the correlation between the pharmacokinetic profile of panobinostat drug levels and the pharmacodynamic effect of panobinostat on histone acetylation in peripheral blood mononuclear cells (PBMCs).
- To determine the effect of panobinostat on histone acetylation and chromatin remodeling proteins (HP-1, DNMT-1, SMC1-5, Topo II).
- To determine the relevance of HDAC1, HDAC2, HDAC3, and HDAC6 expression in PBMCs as a pharmacological marker and in biopsied tumors as a predictive marker for response in patients treated at the MTD.
- To document any objective response in these patients.
OUTLINE: This is a dose-escalation study of panobinostat.
Patients receive oral panobinostat on days 1, 3, and 5 and epirubicin hydrochloride IV on day 5. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during course 1 for panobinostat pharmacokinetic studies. Patients enrolled in the dose expansion cohort also undergo collection of tumor tissue samples by fine needle aspiration at baseline and on day 5 of course 1 (after panobinostat infusion). Blood and tissue samples are analyzed for histone acetylation, chromatin remodeling genes and proteins (HP-1, DNMT-1, SMC1-5, Topo II), and HDAC enzyme expression by immunofluorescence and western blotting.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00878904
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94143-1711|
|Principal Investigator:||Pamela N. Munster, MD||University of California, San Francisco|