Vinorelbine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Treatment and Liver Dysfunction
Condition: Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Lung Neoplasms; Liver Diseases
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.

      PURPOSE: This pilot trial is studying the side effects and best dose of vinorelbine in
      treating patients with advanced solid tumors that have not responded to treatment and liver
      dysfunction.
    

Detailed description: 
      OBJECTIVES:

        -  To correlate indocyanine green and lidocaine metabolism with vinorelbine ditartrate
           pharmacokinetics in patients with advanced, refractory solid tumors and varying degrees
           of liver dysfunction.

        -  To determine the pharmacokinetics of vinorelbine ditartrate in these patients.

        -  To test a plan of dose adjustment for vinorelbine ditartrate administration in these
           patients.

      OUTLINE: Patients are stratified according to extent of clinical liver dysfunction (normal vs
      mild vs moderate vs severe).

      Patients receive dose-adjusted vinorelbine ditartrate IV over 10 minutes once weekly in the
      absence of disease progression or unacceptable toxicity. Patients achieving an objective
      complete response receive 2 additional courses of study therapy.

      Patients undergo blood sample collection periodically during study for pharmacokinetic and
      pharmacodynamic correlative studies. Blood is also collected after patients receive lidocaine
      IV push and indocyanine green (ICG) IV push. Samples are analyzed for whole blood and plasma
      concentrations of vinorelbine ditartrate and its metabolites by high performance liquid
      chromatography (15) or by liquid chromatography/tandem mass spectrometry assay. Samples are
      also analyzed for ICG clearance and lidocaine hydrochloride metabolic capacity by fluorescent
      polarization immunoassay.

      After completion of study therapy, patients are followed periodically.
    

Intervention name(s): indocyanine green; lidocaine; vinorelbine ditartrate; high performance liquid chromatography; intracellular fluorescence polarization analysis; liquid chromatography; mass spectrometry; pharmacological study
Intervention type(s): Drug; Drug; Drug; Other; Other; Other; Other; Other
Intervention description(s): 0.5 mg/kg will be administered by IV push to determine clearance; 1 mg/kg will be administered to determine metabolic capacity; Varying doses ranging from 30 mg/m2 to 7.5 mg/m2 will be administered based upon liver function; Used to determine plasma concentrations of vinorelbine; Used to determine concentration of lidocaine metabolic capacity; Used to determine concentrations of vinorelbine and its metabolites; Used to determine concentrations of vinorelbine and its metabolites; Determination of concentrations of vinorelbine and its metabolites
Intervention MeSH terms: Vinorelbine; Lidocaine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified adult solid tumor, protocol specific; recurrent non-small cell lung cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer