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

• Sponsor: Mast Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00432562
• Collaborator: Synteract, Inc. (Industry), Thywill Latam Solutions SRL (Other), OCASA Soluciones Logísticas S.A. (Other), Worldwide Clinical Trials (Other)
• Enrollment: 31
• Locations: 5
• Duration (Months): 10
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Non-small Cell Lung Cancer; Non-Hodgkins Lymphoma	Drug: Vinorelbine Tartrate	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Bioequivalence Study of Vinorelbine Tartrate Injectable Emulsion (ANX-530) in Patients With Advanced Cancer.
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Outcome Measures

Primary Outcome Measures

1. Time to Reach Maximum Observed Plasma Concentration (Tmax) [0-144 hours post dose]

2. Maximum Observed Plasma Concentration (Cmax) [0-144 hours post-dose]

3. 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

4. Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) [0-144 hours post-dose]

   AUCinf = AUClast + (Clast/lamda z)

5. Percentage of AUCinf Based on Extrapolation (AUCextrap) [0-144 hours post-dose]

6. 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

7. Observed Terminal Elimination Half-Life (t1/2) [0-144 hours post-dose]

   t1/2 = [ln(2)/λ z]

8. Time of Last Measurable Concentration (Tlast) [0-144 hours post-dose]

9. Last Quantifiable Drug Concentration (Clast) [0-144 hours post-dose]

10. Mean Residence Time (MRTinf) [0-144 hours post-dose]

    MRT = (AUMCinf)/(AUCinf)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Investigative Site	Buenos Aires		Argentina
2	Clinical Investigative Site	Mendoza		Argentina
3	Clinical Investigative Site	Rosario		Argentina
4	Clinical Investigative Site	Santa Fe		Argentina
5	Clinical Investigative Site	Tucuman		Argentina

Sponsors and Collaborators

• Mast Therapeutics, Inc.
• Synteract, Inc.
• Thywill Latam Solutions SRL
• OCASA Soluciones Logísticas S.A.
• Worldwide Clinical Trials

Investigators

• Principal Investigator: Lino Arboit, M.D., Fundación Centro Oncológico de Integración Regional - COIR.
• Principal Investigator: Gerardo F Arroyo, M.D., Hospital Privado De Santa Clara De Asis
• Principal Investigator: Cesar R Blajman, M.D., Isis Clínica Especializada
• Principal Investigator: Matias Chacon, M.D., Instituto Médico Espcializado Alexander Fleming
• Principal Investigator: Luis E Fein, M.D., Centro Oncológico
• Principal Investigator: Hugo R. Requejo, M.D., Hospital Regional De Concepción
• Principal Investigator: Edgar P Quintana, M.D., CIMA Salud

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00432562
• Other Study ID Numbers: 530-01
• First Posted: Feb 8, 2007
• Last Update Posted: Feb 23, 2012
• Last Verified: Jan 1, 2012

• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Lymphoma, Non-Hodgkin; Vinorelbine

Study Results

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 Detail	Pre-screening data was not collected for this study

Arm/Group Title	ANX-530/Navelbine	Navelbine/ANX-530
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	16	15
COMPLETED	13	15
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	ANX-530/Navelbine	Navelbine/ANX-530	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	16	15	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 68.8%	10 66.7%	21 67.7%
>=65 years	5 31.3%	5 33.3%	10 32.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (12.77)	58.0 (13.34)	60.2 (13.00)
Sex: Female, Male (Count of Participants)
Female	14 87.5%	12 80%	26 83.9%
Male	2 12.5%	3 20%	5 16.1%
Region of Enrollment (participants) [Number]
Argentina	16 100%	15 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame	0-144 hours post dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	31
Mean (Standard Deviation) [hours]	0.35 (0.13)	0.34 (0.08)

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	31
Mean (Standard Deviation) [ng/mL]	227 (108)	223 (125)

3. Primary Outcome

Title	Area Under the Plasma Concentratio-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast)
Description	Determined Using the Linear Trapezoidal Rule
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	31
Mean (Standard Deviation) [hr*ng/mL]	757.8 (363.7)	716.1 (272.6)

4. Primary Outcome

Title	Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf)
Description	AUCinf = AUClast + (Clast/lamda z)
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	30
Mean (Standard Deviation) [hr*ng/mL]	810.1 (400.9)	718.5 (223.5)

5. Primary Outcome

Title	Percentage of AUCinf Based on Extrapolation (AUCextrap)
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	30
Mean (Standard Deviation) [% of participants]	6.23 (2.54) 38.9%	4.72 (3.11) 31.5%

6. Primary Outcome

Title	Observed Elimination Rate Constant Associated With the Terminal Portion of the Curve (λ z)
Description	Estimated via linear regression of the time versus log concentration
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	30
Mean (Standard Deviation) [hr-1]	0.0160 (0.0044)	0.0187 (0.0062)

7. Primary Outcome

Title	Observed Terminal Elimination Half-Life (t1/2)
Description	t1/2 = [ln(2)/λ z]
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	30
Mean (Standard Deviation) [hours]	46.50 (12.43)	40.48 (13.50)

8. Primary Outcome

Title	Time of Last Measurable Concentration (Tlast)
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	31
Mean (Standard Deviation) [hours]	141.83 (12.93)	141.79 (12.92)

9. Primary Outcome

Title	Last Quantifiable Drug Concentration (Clast)
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	31
Mean (Standard Deviation) [ng/mL]	0.819 (0.834)	0.824 (1.31)

10. Primary Outcome

Title	Mean Residence Time (MRTinf)
Description	MRT = (AUMCinf)/(AUCinf)
Time Frame	0-144 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ANX-530	Navelbine
Arm/Group Description
Measure Participants	31	30
Mean (Standard Deviation) [hours]	35.39 (7.90)	31.31 (10.06)

Adverse Events

Time Frame	AEs and their treatment were documented from the time of the first dose of study medication until 30 days after the last dose. Mild, moderate and severe AEs not related to study treatment were followed for approx 30 days after the last study drug dose.
Adverse Event Reporting Description	Events that were serious, life threatening or related to study treatment were followed until resolution, downgrading of an SAE to non-serious, subject death, start of new cancer therapy or re-assessment of the event's relationship to study medication.
Arm/Group Title	ANX-530/Navelbine		Navelbine/ANX-530
Arm/Group Description	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. Serious Adverse Events are reported by treatment-sequence group and not by study therapy group.		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. Serious Adverse Events are reported by treatment-sequence group and not by study therapy group.
All Cause Mortality
	ANX-530/Navelbine		Navelbine/ANX-530
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ANX-530/Navelbine		Navelbine/ANX-530
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/16 (31.3%)		1/15 (6.7%)
Blood and lymphatic system disorders
ANAEMIA	1/16 (6.3%)		0/15 (0%)
LEUKOPENIA	1/16 (6.3%)		0/15 (0%)
NEUTROPENIA	3/16 (18.8%)		0/15 (0%)
THROMBOCYTOPENIA	1/16 (6.3%)		0/15 (0%)
Infections and infestations
FEBRILE INFECTION	1/16 (6.3%)		1/15 (6.7%)
GENITAL INFECTION FEMALE	1/16 (6.3%)		0/15 (0%)
PNEUMONIA	1/16 (6.3%)		0/15 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	1/16 (6.3%)		0/15 (0%)
Nervous system disorders
STUPOR	1/16 (6.3%)		0/15 (0%)
COMA	1/16 (6.3%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE	1/16 (6.3%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	ANX-530/Navelbine		Navelbine/ANX-530
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/31 (67.7%)		22/31 (71%)
Blood and lymphatic system disorders
ANAEMIA	3/31 (9.7%)		3/31 (9.7%)
LEUKOPENIA	6/31 (19.4%)		3/31 (9.7%)
NEUTROPENIA	12/31 (38.7%)		7/31 (22.6%)
THROMBOCYTOPENIA	1/31 (3.2%)		2/31 (6.5%)
Gastrointestinal disorders
ABDOMINAL PAIN	4/31 (12.9%)		0/31 (0%)
CONSTIPATION	5/31 (16.1%)		5/31 (16.1%)
NAUSEA	5/31 (16.1%)		4/31 (12.9%)
VOMITING	2/31 (6.5%)		1/31 (3.2%)
General disorders
ASTHENIA	3/31 (9.7%)		2/31 (6.5%)
INFUSION SITE PHLEBITIS	1/31 (3.2%)		7/31 (22.6%)
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN	2/31 (6.5%)		0/31 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	0/31 (0%)		2/31 (6.5%)
Skin and subcutaneous tissue disorders
RASH	3/31 (9.7%)		1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of data related to the Study, including publication in special medical magazines, or the disclosure at medical congresses shall be previously authorized in writing by the Sponsor, whereby the Principal Investigator should present the material with an anticipation of not less than 60 days as from the publication or medical congress. The Sponsor decides upon the authorship of any publication related to the Study.