Clinical Trials Register

Summary
EudraCT Number:	2012-003530-16
Sponsor's Protocol Code Number:	PM0259CA231B0
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-11-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2012-003530-16

A.3

Full title of the trial

Randomised phase II study evaluating, as first-line chemotherapy, weekly oral vinorelbine as a single-agent versus weekly paclitaxel as a single-agent in estrogen receptor positive, HER2 negative patients with advanced breast cancer.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study evaluating weekly oral vinorelbine versus weekly paclitaxel in a population of patients with advanced breast cancer.

A.4.1

Sponsor's protocol code number

PM0259CA231B0

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PIERRE FABRE MEDICAMENT
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pierre Fabre Medicament
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pierre Fabre Medicament
B.5.2	Functional name of contact point	Gustavo Villanova
B.5.3	Address:
B.5.3.1	Street Address	45 Place Abel Gance
B.5.3.2	Town/ city	Boulogne
B.5.3.3	Post code	92654
B.5.3.4	Country	France
B.5.4	Telephone number	+33149 10 82 65
B.5.5	Fax number	+33149 10 83 28
B.5.6	E-mail	gustavo.villanova@pierre-fabre.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NAVELBINE 20 mg soft-capsules
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Medicament
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vinorelbine tartrate
D.3.9.1	CAS number	125317-39-7
D.3.9.2	Current sponsor code	PM0259
D.3.9.3	Other descriptive name	VINORELBINE TARTRATE
D.3.9.4	EV Substance Code	SUB20777
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NAVELBINE 30 mg, soft capsules
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Medicament
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vinorelbine tartrate
D.3.9.1	CAS number	125317-39-7
D.3.9.2	Current sponsor code	PM0259
D.3.9.3	Other descriptive name	VINORELBINE TARTRATE
D.3.9.4	EV Substance Code	SUB20777
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PACLITAXEL
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.4	EV Substance Code	SUB09583MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

advanced breast cancer with estrogen receptor positive and HER2 negative.

E.1.1.1

Medical condition in easily understood language

Advanced breast cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

to evaluate, as a first-line chemotherapy, the disease control rate (DCR) of weekly oral vinorelbine as a single-agent versus weekly paclitaxel as a single-agent in estrogen receptor positive, HER2 negative patients with advanced breast cancer.

E.2.2

Secondary objectives of the trial

- to evaluate the response rate, duration of response, duration of stable disease, progression free survival, time-to-treatment failure and overall survival of both regimens
- to evaluate the safety profile in both study arms
- to assess the quality of life of patients

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

· Age superior or equal to 18 years
· Histologically confirmed adenocarcinoma of the breast;
· Documented locally recurrent or metastatic disease previously untreated by chemotherapy and not amenable to curative surgery or radiotherapy;
· Estrogen receptor positive disease determined by superior or equal to 10% positive stained cells for estrogen receptor by immunohistochemistry on the primary tumor or on metastatic site whichever the value of progesterone receptor;
· HER2 negative (assessed by 0-1+ IHC or 2+ IHC with FISH or CISH negative) on the primary tumor or on metastatic site;
· Complete staging within 4 weeks prior to randomization;
· Must have measurable disease according to RECIST (version 1.1);
· Women of childbearing potential must be using a medically accepted method of contraception to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months (for patients receiving oral vinorelbine) or 6 months (for patients receiving paclitaxel) after the last dose of study treatment in such a manner that the risk of pregnancy is minimised;
· Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study treatment;
· Patients should have received at least one previous hormone therapy for breast cancer in any stage of the disease;
· Patients who have received adjuvant or neoadjuvant chemotherapy are allowed if relapsing more than 6 months after the end of chemotherapy;
· Patients may have received prior radiotherapy but a minimum of a 4 weeks interval must have elapsed;
· Karnofsky Performance Status superior or equal to 70%;
· Life expectancy superior or equal to 16 weeks;
· Adequate bone marrow, hepatic and renal functions as evidenced by the following:
- Haemoglobin superior or equal to 10 g/dL
- Absolute Neutrophil Count superior or equal to 1.5 x 109/L
- Platelet Count superior or equal to 100 x 109/L
- Total Bilirubin inferior or equal to 1.5 x ULN (ULN: Upper Limit of Normal)
- SGOT/SGPT inferior or equal to 2.5 x ULN
- Alkaline phosphatase < 5 x ULN
- Creatinine Clearance > 40 mL/min, calculated using the Cockroft and Gault formula.
· Absence of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions should be assessed with the patient before randomization in the trial;
· The patient must have access to social insurance if applicable according to the local
regulations;
· The patient must give written (personally signed and dated) informed consent before completing any study-related procedure.

E.4

Principal exclusion criteria

· Female is not eligible to enter the study if :
- pregnant or lactating
- with positive pregnancy test at inclusion;
· Patients with symptoms suggesting CNS involvement or leptomeningeal metastases;
· Concomitant hormonal therapy for advanced breast cancer;
· Malabsorption syndrome or disease significantly affecting gastro-intestinal function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine;
· Prior treatment with chemotherapy in the metastatic setting;
· Patients with dysphagia, or inability to swallow the tablets;
· Other serious illness or medical conditions:
- Clinically significant cardiac disease
- Unstable diabetes
- Uncontrolled hypercalcemia
- Clinically significant active infections (current or in the last two weeks)
- Previous organ allograft
· Current peripheral neuropathy grade 2 according to NCI version 2 criteria;
· Participation in another clinical trial with any investigational drug within 30 days prior to randomization and/or during the study;
· History of another malignancy within the past five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix;
· With known hypersensitivity to vinca alkaloids or taxanes.

E.5 End points

E.5.1

Primary end point(s)

Disease control rate (DCR)

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy will be determined by the assessment of all lesions at baseline, then every 6 weeks until documented disease progression, unacceptable toxicity or patient’s refusal.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy will be determined at baseline, then every 6 weeks until documented disease progression, unacceptable toxicity or patient’s refusal.

Clinical safety will be assessed at baseline, within each cycle, and at the end of the study

Quality of life assessment: questionnaires will be filled in at baseline before randomisation, then immediately before cycle 2, cycle 4, cycle 6 etc… and at the end of study treatment.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of Life

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Austria

Brazil

France

Italy

Poland

Spain

Switzerland

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study period is defined as the date of last progression in the study.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

124

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

124

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

124

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Described in protocol.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-06-16

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