Vinorelbine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Treatment and Liver Dysfunction
- Conditions
- Unspecified Adult Solid Tumor, Protocol SpecificLung Cancer
- Interventions
- Other: high performance liquid chromatographyOther: intracellular fluorescence polarization analysisOther: liquid chromatographyOther: mass spectrometryOther: pharmacological study
- Registration Number
- NCT00540982
- Lead Sponsor
- City of Hope Medical Center
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 47
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normal Liver Function intracellular fluorescence polarization analysis - Mild Liver Dysfunction high performance liquid chromatography - Severe Liver Dysfunction indocyanine green - Severe Liver Dysfunction mass spectrometry - Moderate Liver Dysfunction high performance liquid chromatography - Moderate Liver Dysfunction liquid chromatography - Severe Liver Dysfunction intracellular fluorescence polarization analysis - Severe Liver Dysfunction vinorelbine ditartrate - Normal Liver Function pharmacological study - Mild Liver Dysfunction intracellular fluorescence polarization analysis - Normal Liver Function vinorelbine ditartrate - Mild Liver Dysfunction liquid chromatography - Mild Liver Dysfunction mass spectrometry - Mild Liver Dysfunction pharmacological study - Moderate Liver Dysfunction intracellular fluorescence polarization analysis - Severe Liver Dysfunction liquid chromatography - Moderate Liver Dysfunction mass spectrometry - Normal Liver Function high performance liquid chromatography - Normal Liver Function liquid chromatography - Normal Liver Function mass spectrometry - Mild Liver Dysfunction vinorelbine ditartrate - Moderate Liver Dysfunction indocyanine green - Moderate Liver Dysfunction vinorelbine ditartrate - Severe Liver Dysfunction pharmacological study - Moderate Liver Dysfunction pharmacological study - Severe Liver Dysfunction high performance liquid chromatography - Severe Liver Dysfunction lidocaine - Normal Liver Function indocyanine green - Normal Liver Function lidocaine - Mild Liver Dysfunction lidocaine - Mild Liver Dysfunction indocyanine green - Moderate Liver Dysfunction lidocaine -
- Primary Outcome Measures
Name Time Method Number of Participants With Grade 3 and 4 Toxicities 3 weeks after the stop of treatment Grade 3 \& 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 2.0.
Area Under the Curve 2 months post treatment Pharmacokinetics were evaluated in patients with sufficient dosing information and plasma concentration versus time data over 0-24 hours following vinorelbine infusion to allow calculation of area-under-the-curve from zero to 24 hours after infusion (AUC0-24). Furthermore, dose-normalization of AUC0-24 to the standard 30 mg/m2 dose was performed to allow evaluation of the relationship between liver function and AUC of vinorelbine. Data were collected at 0 and 24 hours post-dose.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
City of Hope Medical Group
🇺🇸Pasadena, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States