A Phase I Trial of Panobinostat (LBH589) and Epirubicin in Patients With Solid Tumor Malignancies
- 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.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response as assessed by RECIST criteria
30 post end of study drug estimated to be ~24 weeks
Pamela N. Munster, MD
University of California, San Francisco
United States: Food and Drug Administration
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|