Clinical trial NCT00540982: Vinorelbine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Treatment and Liver Dysfunction
Official title: Pilot Pharmacokinetic Study of Dose Adjustment of Vinorelbine in Patients With Varying Degree of Liver Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-08
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Area Under the Curve
timeFrame: 2 months post treatment
measure: Number of Participants With Grade 3 and 4 Toxicities
timeFrame: 3 weeks after the stop of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: City of Hope Medical Group
state: California
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Joseph Chao, MD
role: STUDY_CHAIR
References: