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

18 Years
Not Enrolling
Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


- 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

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.

Inclusion Criteria


- 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


- 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


- See Disease Characteristics

- Recovered from prior therapy

- At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Correlation of indocyanine green and lidocaine metabolism with vinorelbine ditartrate pharmacokinetics

Outcome Time Frame:

2 months post treatment

Safety Issue:


Principal Investigator

Joseph Chao, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Beckman Research Institute


United States: Federal Government

Study ID:




Start Date:

December 1996

Completion Date:

May 2010

Related Keywords:

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



City of Hope Comprehensive Cancer Center Duarte, California  91010
City of Hope Medical Group Pasadena, California  91105