Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Recurrence

Liver Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Hematinics

Vinorelbine

Lidocaine

Liver Extracts

Anesthetics

Anesthetics, Local

Sodium Channel Blockers

Diuretics, Potassium Sparing

Tubulin Modulators

Antimitotic Agents

0.5 mg/kg will be administered by IV push to determine clearance

indocyanine green

1 mg/kg will be administered to determine metabolic capacity

lidocaine

Varying doses ranging from 30 mg/m2 to 7.5 mg/m2 will be administered based upon liver function

vinorelbine ditartrate

Used to determine plasma concentrations of vinorelbine

high performance liquid chromatography

Used to determine concentration of lidocaine metabolic capacity

intracellular fluorescence polarization analysis

Used to determine concentrations of vinorelbine and its metabolites

liquid chromatography

mass spectrometry

Determination of concentrations of vinorelbine and its metabolites

pharmacological study

Joseph Chao, MD

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.

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.

Vinorelbine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Treatment and Liver Dysfunction

Pilot Pharmacokinetic Study of Dose Adjustment of Vinorelbine in Patients With Varying Degree of Liver Dysfunction

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.

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.

National Cancer Institute (NCI)

City of Hope Medical Center

"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Normal Liver Function Group with 30 mg/m2 of Vinorelbine.

Normal (30mg/m2)

Mild Liver Dysfunction Group with 30 mg/m2 of Vinorelbine.

Mild (30mg/m2)

Mild Liver Dysfunction Group with 20 mg/m2 of Vinorelbine.

Mild (20mg/m2)

Mild Liver Dysfunction Group with 15 mg/m2 of Vinorelbine.

Mild (15mg/m2)

Moderate Liver Dysfunction Group with 30 mg/m2 of Vinorelbine.

Moderate (30mg/m2)

Moderate Liver Dysfunction Group with 15 mg/m2 of Vinorelbine.

Moderate (15mg/m2)

Severe Liver Dysfunction Group with 20 mg/m2 of Vinorelbine.

Severe (20mg/m2)

Severe Liver Dysfunction Group with 7.5 mg/m2 of Vinorelbine.

Severe (7.5mg/m2)

All patients with treatment-refractory solid tumors enrolled on the study.

All Patients

Age, Continuous

Sex: Female, Male

Caucasian

Hispanic

Asian

African American

Race/Ethnicity, Customized

United States

Region of Enrollment

Paul Frankel, Ph.D.

Patients were administered weekly 30mg/m2 of vinorelbine as a short IV infusion (over 10 minutes maximum).

Normal liver function was defined as bilirubin \<1.5 mg/dL

Normal

Patients were administered weekly 30mg/m2, 20mg/m2 or 15mg/m2 of vinorelbine as a short IV infusion (over 10 minutes maximum).

Mild liver dysfunction defined as bilirubin \<1.5 mg/dL and ≥1 of the following: AST/ALT 1.5-2.5 X ULN or ALK 1.5-3 X ULN

Mild

Patients were administered weekly 30mg/m2 or 15mg/m2 of vinorelbine as a short IV infusion (over 10 minutes maximum).

Moderate liver dysfunction was defined as bilirubin 1.5-3.0 mg/dL and/or ≥1 of the following: AST/ALT \>2.5 X ULN or ALK \>3 X ULN.

Moderate

Patients were administered weekly 20mg/m2 or 7.5mg/m2 of vinorelbine as a short IV infusion (over 10 minutes maximum).

Severe liver dysfunction was defined as bilirubin \>3.0 mg/dL.

Spots Global Cancer Trial Database for intracellular fluorescence polarization analysis