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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00540982
• Other study ID #: 96032
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 1996
• Est. completion date: May 20, 2010

Study information

• Verified date: January 2019
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: May 20, 2010
• Est. primary completion date: May 20, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor

• Any histology allowed

• Refractory to standard therapy OR no standard therapy exists

• Previously untreated non-small cell lung cancer allowed, provided abnormal liver function is present, defined as moderate (group 3) or severe (group 4)

• Measurable disease not required

• Present measurable disease requires baseline measurements within 4 weeks of study entry

• Patients with acute hepatitis from viral or drug etiologies should recover to a stable baseline prior to study therapy

• History of brain metastasis allowed, provided the following criteria are met:

• Metastasis has been controlled by radiotherapy or surgery

• Patient is not currently on corticosteroids

• Neurologic status is stable

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%

• Life expectancy = 2 months

• ANC = 1,500/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 10 g/dL (transfusion to this level allowed)

• Creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/ min

• Patients with EKG evidence of first- or second-degree AV block or left or right bundle branch block are ineligible for the lidocaine bolus, but may otherwise be treated on this protocol

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No concurrent illness (e.g., cardiovascular, pulmonary, or central nervous system) that is poorly controlled or of such severity that the investigator deems unwise to enter the patient on protocol

• Must have ability to comply with study treatment and required tests

• Obstructive jaundice requires a drainage procedure prior to study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea therapy)

• No prior radiotherapy to > 30% of the bone marrow or more than standard adjuvant pelvic radiotherapy for rectal cancer

Related Conditions & MeSH terms

• Liver Diseases
• Lung Cancer
• Lung Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• indocyanine green
0.5 mg/kg will be administered by IV push to determine clearance
• lidocaine
1 mg/kg will be administered to determine metabolic capacity
• vinorelbine ditartrate
Varying doses ranging from 30 mg/m2 to 7.5 mg/m2 will be administered based upon liver function

Other:
• high performance liquid chromatography
Used to determine plasma concentrations of vinorelbine
• intracellular fluorescence polarization analysis
Used to determine concentration of lidocaine metabolic capacity
• liquid chromatography
Used to determine concentrations of vinorelbine and its metabolites
• mass spectrometry
Used to determine concentrations of vinorelbine and its metabolites
• pharmacological study
Determination of concentrations of vinorelbine and its metabolites

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	City of Hope Medical Group	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve	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.	2 months post treatment
Primary	Number of Participants With Grade 3 and 4 Toxicities	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.	3 weeks after the stop of treatment