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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00540982
First received: October 5, 2007
Last updated: July 16, 2012
Last verified: July 2012

October 5, 2007
July 16, 2012
December 1996
May 2010   (final data collection date for primary outcome measure)
  • Correlation of indocyanine green and lidocaine metabolism with vinorelbine ditartrate pharmacokinetics [ Time Frame: 2 months post treatment ] [ Designated as safety issue: No ]
  • Pharmacokinetics of vinorelbine ditartrate as measured by high performance liquid chromatography (15) or by liquid chromatography/tandem mass spectrometry assay [ Time Frame: 2 months post treatment ] [ Designated as safety issue: No ]
  • Test of dose adjustment of vinorelbine ditartrate [ Time Frame: 2 months post treatment ] [ Designated as safety issue: No ]
  • Correlation of indocyanine green and lidocaine metabolism with vinorelbine ditartrate pharmacokinetics
  • Pharmacokinetics of vinorelbine ditartrate as measured by high performance liquid chromatography (15) or by liquid chromatography/tandem mass spectrometry assay
  • Test of dose adjustment of vinorelbine ditartrate
Complete list of historical versions of study NCT00540982 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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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

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: indocyanine green
    0.5 mg/kg will be administered by IV push to determine clearance
  • Drug: lidocaine
    1 mg/kg will be administered to determine metabolic capacity
  • Drug: 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
  • Other: intracellular fluorescence polarization analysis
    Used to determine concentration of lidocaine metabolic capacity
  • Other: liquid chromatography
    Used to determine concentrations of vinorelbine and its metabolites
  • Other: mass spectrometry
    Used to determine concentrations of vinorelbine and its metabolites
  • Other: pharmacological study
    Determination of concentrations of vinorelbine and its metabolites
  • Experimental: Normal Liver Function
    Interventions:
    • Drug: indocyanine green
    • Drug: lidocaine
    • Drug: vinorelbine ditartrate
    • Other: high performance liquid chromatography
    • Other: intracellular fluorescence polarization analysis
    • Other: liquid chromatography
    • Other: mass spectrometry
    • Other: pharmacological study
  • Experimental: Mild Liver Dysfunction
    Interventions:
    • Drug: indocyanine green
    • Drug: lidocaine
    • Drug: vinorelbine ditartrate
    • Other: high performance liquid chromatography
    • Other: intracellular fluorescence polarization analysis
    • Other: liquid chromatography
    • Other: mass spectrometry
    • Other: pharmacological study
  • Experimental: Moderate Liver Dysfunction
    Interventions:
    • Drug: indocyanine green
    • Drug: lidocaine
    • Drug: vinorelbine ditartrate
    • Other: high performance liquid chromatography
    • Other: intracellular fluorescence polarization analysis
    • Other: liquid chromatography
    • Other: mass spectrometry
    • Other: pharmacological study
  • Experimental: Severe Liver Dysfunction
    Interventions:
    • Drug: indocyanine green
    • Drug: lidocaine
    • Drug: vinorelbine ditartrate
    • Other: high performance liquid chromatography
    • Other: intracellular fluorescence polarization analysis
    • Other: liquid chromatography
    • Other: mass spectrometry
    • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
47
May 2010
May 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00540982
96032, P30CA033572, CHNMC-96032, CDR0000567457
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Study Chair: Joseph Chao, MD Beckman Research Institute
City of Hope Medical Center
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP