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

Primary Purpose

Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

indocyanine green

lidocaine

vinorelbine ditartrate

high performance liquid chromatography

intracellular fluorescence polarization analysis

liquid chromatography

mass spectrometry

pharmacological study

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

City of Hope Comprehensive Cancer Center
City of Hope Medical Group

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Normal Liver Function

Mild Liver Dysfunction

Moderate Liver Dysfunction

Severe Liver Dysfunction

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00540982

First Posted

October 5, 2007

Last Updated

March 6, 2019

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00540982

Brief Title

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

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

December 1996 (undefined)

Primary Completion Date

May 20, 2010 (Actual)

Study Completion Date

May 20, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Liver Function

Arm Type

Experimental

Arm Title

Mild Liver Dysfunction

Arm Type

Experimental

Arm Title

Moderate Liver Dysfunction

Arm Type

Experimental

Arm Title

Severe Liver Dysfunction

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

indocyanine green

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

lidocaine

Intervention Description

1 mg/kg will be administered to determine metabolic capacity

Intervention Type

Drug

Intervention Name(s)

vinorelbine ditartrate

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

high performance liquid chromatography

Intervention Description

Used to determine plasma concentrations of vinorelbine

Intervention Type

Other

Intervention Name(s)

intracellular fluorescence polarization analysis

Intervention Description

Used to determine concentration of lidocaine metabolic capacity

Intervention Type

Other

Intervention Name(s)

liquid chromatography

Intervention Description

Used to determine concentrations of vinorelbine and its metabolites

Intervention Type

Other

Intervention Name(s)

mass spectrometry

Intervention Description

Used to determine concentrations of vinorelbine and its metabolites

Intervention Type

Other

Intervention Name(s)

pharmacological study

Intervention Description

Determination of concentrations of vinorelbine and its metabolites

Primary Outcome Measure Information:

Title

Area Under the Curve

Description

Time Frame

2 months post treatment

Title

Number of Participants With Grade 3 and 4 Toxicities

Description

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.

Time Frame

3 weeks after the stop of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph Chao, MD

Organizational Affiliation

City of Hope Comprehensive Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

City of Hope Comprehensive Cancer Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010-3000

Country

United States

Facility Name

City of Hope Medical Group

City

Pasadena

State/Province

California

ZIP/Postal Code

91105

Country

United States

12. IPD Sharing Statement

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

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