Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors
Condition: Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  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.

      Secondary

        -  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.
    

Intervention name(s): epirubicin hydrochloride; panobinostat; gene expression analysis; protein expression analysis; western blotting; immunologic technique; laboratory biomarker analysis; pharmacological study
Intervention type(s): Drug; Drug; Genetic; Genetic; Genetic; Other; Other; Other
Intervention MeSH terms: Epirubicin; Panobinostat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified adult solid tumor, protocol specific