A Bioequivalence Study of Vinorelbine Tartrate Injectable Emulsion in Patients With Advanced Cancer.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Non-small Cell Lung Cancer, Non-Hodgkins Lymphoma

Intervention / Treatment
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* Drug: Vinorelbine Tartrate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0-144 hours post dose | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0-144 hours post-dose | 
| 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 | 0-144 hours post-dose | 
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) | AUCinf = AUClast + (Clast/lamda z) | 0-144 hours post-dose | 
| Percentage of AUCinf Based on Extrapolation (AUCextrap) |  | 0-144 hours post-dose | 
| Observed Elimination Rate Constant Associated With the Terminal Portion of the Curve (λ z) | Estimated via linear regression of the time versus log concentration | 0-144 hours post-dose | 
| Observed Terminal Elimination Half-Life (t1/2) | t1/2 = [ln(2)/λ z] | 0-144 hours post-dose | 
| Time of Last Measurable Concentration (Tlast) |  | 0-144 hours post-dose | 
| Last Quantifiable Drug Concentration (Clast) |  | 0-144 hours post-dose | 
| Mean Residence Time (MRTinf) | MRT = (AUMCinf)/(AUCinf) | 0-144 hours post-dose |