Clinical Trials Register

Summary
EudraCT Number:	2012-003361-18
Sponsor's Protocol Code Number:	PM0259CA229J1
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-06
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2012-003361-18

A.3

Full title of the trial

Phase II trial of oral vinorelbine in Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) positive mutation after a failure to treatment with EGFR Tyrosine Kinase Inhibitors (TKI) in first line.

A.3.1

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

Phase II trial of oral vinorelbine in a population of patients with lung cancer with an EGFR mutation, after failure to treatment with TKI in first line.

A.4.1

Sponsor's protocol code number

PM0259CA229J1

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	Marcello RIGGI
B.5.3	Address:
B.5.3.1	Street Address	45 PLACE ABEL GANCE
B.5.3.2	Town/ city	BOULOGNE BILLANCOURT
B.5.3.3	Post code	92100
B.5.3.4	Country	France
B.5.4	Telephone number	+330149108177
B.5.5	Fax number	+330149108328
B.5.6	E-mail	marcello.riggi@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® oral/Capsule, soft, 20mg
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® oral/Capsule, soft, 30mg
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.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

Patients with:
-Histologically or cytologically confirmed NSCLC (stage IIIB or IV) and
-epidermal growth factor receptor (EGFR) positive mutation and
-previously treated with tyrosine kinase inhibitor (gefitinib or erlotinib)

E.1.1.1

Medical condition in easily understood language

Patients with lung cancer and epidermal growth factor receptor (EGFR) positive mutation, previously treated with tyrosine kinase inhibitor

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10029515
E.1.2	Term	Non-small cell lung cancer recurrent
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 the disease control rate (CR, PR, SD) of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor

E.2.2

Secondary objectives of the trial

To evaluate efficacy and safety parameters :
The Duration of Disease Control,
The Objective Response Rate and Duration of Response,
The Time to First Response,
Duration of Stable Disease,
The Progression-Free Survival (PFS),
Time To Treatment Failure (TTF),
The Overall Survival (OS),
The tolerance
in the setting of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- The patient must give written (personally signed and dated) informed consent before completing any study-related procedure.
- Patients > or = 18 years.
- Histologically or cytologically confirmed NSCLC.
- Patients with epidermal growth factor receptor (EGFR) positive mutation.
- Patients progressing or relapsing after treatment with EGFR tyrosine kinase inhibitors but a minimum of 2 weeks must have elapsed prior to start of study treatment.
- Performance status KPS > or = 70% (ECOG/WHO PS 0-1).
- Stage IIIB (with supra-clavicular nodal metastases), stage IV.
- Life expectancy more than 12 weeks.
- Adequate bone marrow, hepatic and renal functions:
Neutrophils > or = 2.0 x 10^9/l, Platelets > or = 100 x 10^9/l, Haemoglobin > or = 10.0 g/dL;
Total bilirubin < or = 1.5 x ULN (Upper Limit of Normal), Transaminases (ALT, AST) < 2.5 x ULN, Alkaline Phosphatases < 5 x ULN;
Calculated creatinine clearance > or = 40 ml/min (Cockcroft and Gault formula).
- Prior therapy:
Chemotherapy: patient must not have had systemic chemotherapy or
immunotherapy (monoclonal antibody);
Radiation therapy: patient is eligible if presence of target lesions outside the irradiated area. A minimum of 2 weeks must have elapsed prior to start of study treatment.
- Presence of at least one measurable lesion (measured in at least one dimension) which has not been previously irradiated (RECIST criteria – version 1.1). Physical examination and ultrasound will not be considered as objective tumour assessments.
- Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial.
- Women of childbearing potential must be using a medically accepted method of contraception (i.e. oral contraceptives, intrauterine devices) to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months 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.
- Fertile men must be using an effective method of birth control if their partners are women of childbearing potential throughout the study period and for up to 3 months after the last dose of study treatment.
- The patient must have access to social insurance according to local regulations.

E.4

Principal exclusion criteria

Patients with at least one of the following criteria will not be included:
- Known hypersensitivity to the study drug or to drugs with similar chemical structures.
- Participation in another clinical trial with any experimental drug (except approved EGFR-TKIs) within the 30 days before registration and/or during the study.
- Any important factor likely to modify drug absorption (e.g. surgery of the gastrointestinal tract, significant malabsorption syndrome or disease affecting the gastrointestinal tract function).
- Previous radiotherapy in the only site used to assess response.
- Clinically relevant or unstable systemic disease making implementation of the protocol difficult.
- Active brain metastases except for the followings:
Asymptomatic brain metastases
incidentally found during screening process which does not require local treatment in the opinion of the investigator (2nd cohort, postamendment
PA04).
Asymptomatic brain metastases for which local treatment has been given: at least 1 week off corticosteroids and/or anticonvulsants treatment before study
registration (2nd cohort, postamendment PA04).
- Meningeal carcinomatosis.
- Symptomatic neuropathy (sensory) > or = grade 2 according to the NCI Common Toxicity Criteria (NCI – CTC version 2).
- Weight loss > 10% within the previous 3 months.
- Long term oxygen therapy.
- Concomitant/uncontrolled medical disorder (cardiac failure or myocardial infarction within the previous 3 months, uncontrolled hypertension or arrhythmia, uncontrolled hypercalcaemia, active infection requiring i.v. antibiotics within 2 weeks before the beginning of treatment).
- Women if pregnant or lactating or with positive pregnancy test at inclusion;
- Women of childbearing potential who did not use or is unwilling or unable to use an acceptable method to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment.
- Sexually active fertile men not using effective method of birth control method throughout the study period and for up to 3 months after the last dose of study treatment if his partner is a woman of childbearing potential.
- Other malignancies except adequately treated basal carcinoma of the skin, in-situ cervix carcinoma or any other tumor with a disease free interval > 5 years.

E.5 End points

E.5.1

Primary end point(s)

To evaluate the disease control rate (CR, PR, SD) of oral vinorelbine as
a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor

E.5.1.1

Timepoint(s) of evaluation of this end point

Tumour assessment will be performed according to the RECIST guideline (version 1.1). Assessment of measurable disease will be carried out at baseline and every 6 weeks until disease progression.

E.5.2

Secondary end point(s)

To evaluate efficacy and safety parameters
the objective response rate.
the duration of the disease control,
the duration of stable disease
the duration of response,
the time to first response,
the time to Treatment Failure (TTF),
the Progression Free Survival (PFS),
the Overall Survival (OS).
the tolerance in this setting

of oral vinorelbine as a single agent in patients with lung cancer and a EGFR positive mutation, previously treated with tyrosine kinase inhibitor.

E.5.2.1

Timepoint(s) of evaluation of this end point

every 6 weeks

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

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

E.8.1.1

Randomised

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)

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

Singapore

Taiwan

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 observed in the study. Survival information will be collected approximately every 3 months until death.

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

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

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

2013-03-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-04-17

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