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.

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00432562

Enrollment

Registered

2007-02-08

Start date

2007-02-28

Completion date

2007-12-31

Last updated

2012-02-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Brief summary

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

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.

Interventions

DRUGVinorelbine 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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf)	0-144 hours post-dose	AUCinf = AUClast + (Clast/lamda z)
Percentage of AUCinf Based on Extrapolation (AUCextrap)	0-144 hours post-dose	—
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)	0-144 hours post-dose	Determined Using the Linear Trapezoidal Rule
Observed Elimination Rate Constant Associated With the Terminal Portion of the Curve (λ z)	0-144 hours post-dose	Estimated via linear regression of the time versus log concentration
Observed Terminal Elimination Half-Life (t1/2)	0-144 hours post-dose	t1/2 = \[ln(2)/λ z\]
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)	0-144 hours post-dose	MRT = (AUMCinf)/(AUCinf)

Countries

Argentina

Participant flow

Recruitment details

STUDIED PERIOD: First Patient Enrolled: 22 March 2007 Last Patient Completed: 02 November 2007 Study patients were enrolled at seven study sites in Argentina.

Pre-assignment details

Pre-screening data was not collected for this study

Participants by arm

Arm	Count
ANX-530/Navelbine Patients were randomly assigned to receive a single intravenous (IV) dose of 30 mg/m2 of ANX 530 in the first study period, then one week later patients crossed over to receive a single IV dose of 30 mg/m2 of Navelbine in the second study period.	16
Navelbine/ANX-530 Patients were randomly assigned to receive a single intravenous (IV) dose of 30 mg/m2 of Navelbine in the first study period, then one week later patients crossed over to receive a single IV dose of 30 mg/m2 of ANX-530 in the second study period.	15
Total	31

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	3	0

Baseline characteristics

Characteristic	Navelbine/ANX-530	ANX-530/Navelbine	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	5 Participants	5 Participants	10 Participants
Age, Categorical Between 18 and 65 years	10 Participants	11 Participants	21 Participants
Age Continuous	58.0 years STANDARD_DEVIATION 13.34	62.2 years STANDARD_DEVIATION 12.77	60.2 years STANDARD_DEVIATION 13
Region of Enrollment Argentina	15 participants	16 participants	31 participants
Sex: Female, Male Female	12 Participants	14 Participants	26 Participants
Sex: Female, Male Male	3 Participants	2 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	21 / 31	22 / 31
serious Total, serious adverse events	5 / 16	1 / 15