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

NCT00540982 | Completed Phase 1 Results DMC

• 4 other identifiers: 96032P30CA033572CHNMC-96032CDR0000567457
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (2)

• Area Under the Curve

  Pharmacokinetics were evaluated in patients with sufficient dosing information and plasma concentration versus time data over 0-24 hours following vinorelbine infusion to allow calculation of area-under-the-curve from zero to 24 hours after infusion (AUC0-24). Furthermore, dose-normalization of AUC0-24 to the standard 30 mg/m2 dose was performed to allow evaluation of the relationship between liver function and AUC of vinorelbine. Data were collected at 0 and 24 hours post-dose.

  2 months post treatment

• Number of Participants With Grade 3 and 4 Toxicities

  Grade 3 \& 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 2.0.

  3 weeks after the stop of treatment

Study Arms (4)

Normal Liver Function

EXPERIMENTAL

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

Mild Liver Dysfunction

EXPERIMENTAL

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

Moderate Liver Dysfunction

EXPERIMENTAL

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

Severe Liver Dysfunction

EXPERIMENTAL

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

Interventions

indocyanine green DRUG

0.5 mg/kg will be administered by IV push to determine clearance

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

lidocaine DRUG

1 mg/kg will be administered to determine metabolic capacity

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

vinorelbine ditartrate DRUG

Varying doses ranging from 30 mg/m2 to 7.5 mg/m2 will be administered based upon liver function

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

high performance liquid chromatography OTHER

Used to determine plasma concentrations of vinorelbine

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

intracellular fluorescence polarization analysis OTHER

Used to determine concentration of lidocaine metabolic capacity

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

liquid chromatography OTHER

Used to determine concentrations of vinorelbine and its metabolites

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

mass spectrometry OTHER

Used to determine concentrations of vinorelbine and its metabolites

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

pharmacological study OTHER

Determination of concentrations of vinorelbine and its metabolites

Mild Liver Dysfunction; Moderate Liver Dysfunction; Normal Liver Function; Severe Liver Dysfunction

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

City of Hope Medical Group

Pasadena, California, 91105, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Indocyanine Green; Lidocaine; Vinorelbine; Chromatography, High Pressure Liquid; Chromatography, Liquid; Mass Spectrometry

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indolizidines; Indolizines; Chromatography; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Joseph Chao

  City of Hope Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2007
• First Posted: October 8, 2007
• Study Start: February 20, 1997
• Primary Completion: May 20, 2010
• Study Completion: May 20, 2010
• Last Updated: July 2, 2025
• Results First Posted: March 11, 2019

Record last verified: 2025-06

Locations

US (2)