Title

A Bioequivalence Study of Vinorelbine Tartrate Injectable Emulsion in Patients With Advanced Cancer.
A Bioequivalence Study of Vinorelbine Tartrate Injectable Emulsion (ANX-530) in Patients With Advanced Cancer.
  • Phase

    Phase 1
  • Study Type

    Interventional
  • Intervention/Treatment

    vinorelbine ...
  • Study Participants

    31
This study was a randomized, single dose crossover comparison of the investigational product with a Reference Product (vinorelbine tartrate injection, NAVELBINE®). The primary objective was to demonstrate the equivalence of ANX-530 and the Reference Product, NAVELBINE.
ANX-530 (vinorelbine tartrate injectable emulsion), an investigational drug, is an oil-in-water emulsion of vinorelbine tartrate composed of an oil phase and emulsifier dispersed in an aqueous solution. ADVENTRX Pharmaceuticals, Inc. of San Diego, California, developed ANX-530 as a vinorelbine tartrate formulation to be used in clinical settings where Vinorelbine Tartrate Injection (NAVELBINE) is indicated. Nonclinical toxicology studies suggest either equivalent or less toxicity of ANX-530 compared to Reference Product. In particular, ANX-530 caused less vein toxicity in a rabbit vein irritation model, suggesting ANX-530 could potentially cause less venous irritation than NAVELBINE in a clinical setting. ADVENTRX is investigating whether ANX-530 could substitute for NAVELBINE in these settings.
Study Started
Feb 28
2007
Primary Completion
Nov 30
2007
Study Completion
Dec 31
2007
Results Posted
Feb 23
2012
Estimate
Last Update
Feb 23
2012
Estimate

Drug Vinorelbine Tartrate

Subjects received one dose each of ANX-530 and NAVELBINE, each providing 30 mg/m2 vinorelbine. Study drugs will be infused into an arm vein over ten minutes.

  • Other names: Exelbine (proposed), ANX-530

Criteria

Inclusion Criteria:

Age > 18 years.
Advanced cancer potentially sensitive to vinorelbine:
Breast cancer.
Stage 3 or 4 non-small cell lung cancer.
Non-Hodgkins lymphoma.
Cancer of other histologic type, sensitive to vinca alkaloids.
Rare tumor type with no standard treatment, for which single agent vinorelbine is appropriate therapy.
Failure of standard treatment(s) of the tumor.
Life expectancy of at least three months.
ECOG performance level 0-2 or Karnofsky score 100-70.
Hematological and serum chemistry results with defined ranges.
Willingness and ability to provide written informed consent.

Exclusion Criteria:

Pregnancy or lactation. In a woman of childbearing potential, a positive pregnancy test result, no pregnancy test result, or no use of reliable contraception, at baseline. A postmenopausal woman will be considered to be of childbearing potential until there has been amenorrhea for at least 12 consecutive months.
Previous treatment with vinorelbine or mitomycin.
Any history suggesting or demonstrating resistance to, lack of response to, or intolerance of any prior vinca alkaloid treatment.
Active infection.
Prior anticancer therapy completed within four weeks prior to the first day of study treatment.
Failure to have recovered from any toxicity of previous cancer treatment (patients with alopecia will not be excluded).
Participation in another experimental drug study within four weeks prior to the first day of study treatment.
Requirement for any concomitant chemotherapeutic agent other than the study medication.
Any investigator judgment that the individual would not be an appropriate study subject.

Summary

ANX-530/Navelbine

Navelbine/ANX-530

All Events

Event Type Organ System Event Term ANX-530/Navelbine Navelbine/ANX-530

Maximum Observed Plasma Concentration (Cmax)

ANX-530

227.0
ng/mL (Mean)
Standard Deviation: 108

Navelbine

223.0
ng/mL (Mean)
Standard Deviation: 125

Time to Reach Maximum Observed Plasma Concentration (Tmax)

ANX-530

0.35
hours (Mean)
Standard Deviation: 0.13

Navelbine

0.34
hours (Mean)
Standard Deviation: 0.08

Area Under the Plasma Concentratio-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast)

Determined Using the Linear Trapezoidal Rule

ANX-530

757.8
hr*ng/mL (Mean)
Standard Deviation: 363.7

Navelbine

716.1
hr*ng/mL (Mean)
Standard Deviation: 272.6

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf)

AUCinf = AUClast + (Clast/lamda z)

ANX-530

810.1
hr*ng/mL (Mean)
Standard Deviation: 400.9

Navelbine

718.5
hr*ng/mL (Mean)
Standard Deviation: 223.5

Percentage of AUCinf Based on Extrapolation (AUCextrap)

ANX-530

6.23
% of participants (Mean)
Standard Deviation: 2.54

Navelbine

4.72
% of participants (Mean)
Standard Deviation: 3.11

Observed Elimination Rate Constant Associated With the Terminal Portion of the Curve (λ z)

Estimated via linear regression of the time versus log concentration

ANX-530

0.016
hr-1 (Mean)
Standard Deviation: 0.0044

Navelbine

0.0187
hr-1 (Mean)
Standard Deviation: 0.0062

Observed Terminal Elimination Half-Life (t1/2)

t1/2 = [ln(2)/λ z]

ANX-530

46.5
hours (Mean)
Standard Deviation: 12.43

Navelbine

40.48
hours (Mean)
Standard Deviation: 13.50

Time of Last Measurable Concentration (Tlast)

ANX-530

141.83
hours (Mean)
Standard Deviation: 12.93

Navelbine

141.79
hours (Mean)
Standard Deviation: 12.92

Last Quantifiable Drug Concentration (Clast)

ANX-530

0.819
ng/mL (Mean)
Standard Deviation: 0.834

Navelbine

0.824
ng/mL (Mean)
Standard Deviation: 1.31

Mean Residence Time (MRTinf)

MRT = (AUMCinf)/(AUCinf)

ANX-530

35.39
hours (Mean)
Standard Deviation: 7.90

Navelbine

31.31
hours (Mean)
Standard Deviation: 10.06

Total

31
Participants

Age Continuous

60.2
years (Mean)
Standard Deviation: 13.00

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study

ANX-530/Navelbine

Navelbine/ANX-530

Drop/Withdrawal Reasons

ANX-530/Navelbine