Vinorelbine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Treatment and Liver Dysfunction
This study has been completed.
Sponsor:
City of Hope Medical Center
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
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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:
Drug Information available for:
Lidocaine hydrochloride
Lidocaine
Indocyanine green
Vinorelbine
Vinorelbine tartrate
U.S. FDA Resources
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
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 Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013