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
  Purpose

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.


Condition Intervention
Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Pharmacokinetic Study of Dose Adjustment of Vinorelbine in Patients With Varying Degree of Liver Dysfunction

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • 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 ]

Enrollment: 47
Study Start Date: December 1996
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Normal Liver Function 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: Mild Liver Dysfunction 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: Moderate Liver Dysfunction 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: Severe Liver Dysfunction 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00540982

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Joseph Chao, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00540982     History of Changes
Other Study ID Numbers: 96032, P30CA033572, CHNMC-96032, CDR0000567457
Study First Received: October 5, 2007
Last Updated: July 16, 2012
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
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

Additional relevant MeSH terms:
Lung Neoplasms
Liver Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Diseases
Lidocaine
Vinorelbine
Vinblastine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators

ClinicalTrials.gov processed this record on August 18, 2014