Clinical Trials Register

Summary
EudraCT Number:	2005-003926-24
Sponsor's Protocol Code Number:	EGF104900(UM/2005/00071/02)
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-02-17
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2005-003926-24

A.3

Full title of the trial

A Randomized, Multicenter Open-Label Phase III Study of Lapatinib in Combination with Trastuzumab versus Lapatinib Monotherapy in Subjects with Metastatic Breast Cancer whose disease has progressed on Trastuzumab-Containing Regimens

Uno studio di fase III, randomizzato, multicentrico, di Lapatinib in combinazione con Trastuzumab versus monoterapia con Lapatinib in Pazienti con carcinoma mammario metastatico in progressione dopo regimi terapeutici comprendenti Trastuzumab

A.3.2

Name or abbreviated title of the trial where available

A Study of GW572016 (lapatinib) in Advanced Breast Cancer

Uno studio con GW572016 (lapatinib) nel carcinoma

A.4.1

Sponsor's protocol code number

EGF104900(UM/2005/00071/02)

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	GlaxoSmithKline Research and Development Ltd
B.1.3.4	Country	United Kingdom
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
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	LAPATINIB
D.3.2	Product code	GW572016
D.3.4	Pharmaceutical form	Tablet
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	LAPATINIB
D.3.9.2	Current sponsor code	GW572016
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	250
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
D.IMP: 2
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.2.1.1.1	Trade name	HERCEPTIN*EV 1FL 150MG
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE SpA *
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Powder 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	Trastuzumab
D.3.9.1	CAS number	180288-69-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	150
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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

Metastatic breast cancer

Carcinoma mammario metastatico

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	PT
E.1.2	Classification code	10055113
E.1.2	Term	Breast cancer metastatic
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 and compare the two treatment groups with respect to progression-free survival (PFS) in subjects with metastatic breast cancer.

•Valutare e confrontare i due gruppi di trattamento rispetto alla sopravvivenza libera da progressione with (PFS) in soggetti con carcinoma mamario metastatico.

E.2.2

Secondary objectives of the trial

- To evaluate and compare the two treatment groups with respect to the following: overall survival, tumor response rate (complete or partial), clinical benefit (CR, PR, and stable disease for at least 6 months), time to response, duration of response. - To determine the qualitative and quantitative toxicities associated with oral lapatinib administered daily in combination with trastuzumab vs lapatinib monotherapy. - To collect and store serum specimens for comparing baseline and on-treatment serum concentrations of ErbB1 and ErbB2 extracellular domains (ECDs), perform proteomic analysis to detect other shed tumor proteins, identify changes in the protein profile and correlate to treatment response,PGX analysis. - To further characterize the patient population by determination of intra-tumoral expression of ErbB1, ErbB2, and downstream biomarkers which may help elucidate the effects of investigational products on the target and other proteins along relevant pathways in the ty

•Valut e confr.i 2 gruppi di tratt rispetto a:sopravvivenza glob,tasso di risp tumorale,CR,PR,e malattia stabile da almeno 6 mesi,T alla risp,durata della risp•Det.la tossicità qualitativa e quantitativa associata al tratt orale con lapatinib sommin ognigg incomb con trastuzumab vs monoterapia con lapatinib•Raccogliere e conservare campioni di siero per confr.le concentrazioni sieriche basali e durante il tratt dei domini extracellulari di ErbB1 ed ErbB2(ECDs),esegure l'analisi proteomica per evidenziare altre proteine tumorali,identificare modificazioni nel profilo delle proteine e correlarle con la risp al tratt,analisi farmacogenetica•Caratterizzare ulteriormente la pop di pazattr la determinazione della espressione intra-tumorale di ErbB1,ErbB2,e dei biomarc a monte allo scopo di migliorare la comprensione degli eff di lapatinib sulle proteine target e sulle altre proteine di rilievo nel modello delle tirosino-chinasi•QoL e confronto l'impatto sulla QoL fra i 2 gruppi di tratt

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent. 2. Female >18 years. 3. Metastatic breast cancer, histologically/cytologically confirmed. 4. Subjects must have stage IV breast cancer whereby their disease has progressed in either the adjuvant or metastatic setting. Prior therapies must include, but are not limited toTaxane and Anthracycline. 5. Subjects must have received and progressed following treatment with at least TWO trastuzumab plus cytotoxic chemotherapy regimens in the metastatic settingSubjects must have archived tumor tissue available for testing. 6. Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) in primary or metastatic tumor tissue.

1.Firma del consenso informato 2.Donne >18 anni - 3.Carcinoma mammario metastatico, istologicamente/citologicamente confermato 4. I soggetti devono avere un carcinoma mammario di stadio IV per il quale si sia verificata una progressione di malattia in contesto adiuvante o metastatico. Le precedenti terapie dovranno comprendere, ma non saranno limitate a Taxani e Antracicline. 5. I soggetti devono aver ricevuto ed essere andati in progressione dopo il trattamento con almeno DUE regimi di trattamento con trastuzumab piu` chemioterapia citotossica in contesto metastatico. 6. I soggetti devono avere un campione di tessuto tumorale archiviato disponibile da analizzare 7. Documentata amplificazione del gene ErbB2 , tramite fluorescenza con ibridizzazione in situ (FISH), nel tessuto tumorale primario o metastatico.

E.4

Principal exclusion criteria

1. Pregnant or lactating females. 2. Prior therapy with an ErbB1 and/or ErbB2 inhibitor other than trastuzumab. 5. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject`s safety. 10. Known history or clinical evidence of leptomeningeal carcinomatosis. 11. Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy).15. Current active hepatic or biliary disease.

1. Donne in gravidanza o allattamento. 2.Precedente terapia con un inibitore di ErbB1 e/o ErbB2 fatta eccezione per trastuzumab. 5. Malattie o condizioni concomitanti che rendano il soggetto inadeguato alla partecipazione allo studio o qualsiasi grave disturbo clinico che possa interferire con la sicurezza del soggetto 10. Storia pregressa o evidenza clinica di carcinomatosi leptomeningee. 11. Concomitante trattamento antitumorale (chemioterapia, terapia radiante, immunoterapia, terapia biologica, terapia ormonale).15. Malattia epatica o biliare in corso.

E.5 End points

E.5.1

Primary end point(s)

• Progression-free survival Secondary • Overall survival • Overall response rate determined by radiologic evaluation according to Response Evaluation Criteria in Solid Tumors (RECIST) • Clinical benefit (CR, PR or SD for at least 6 months) • Time to response • Time to progression • Duration of response • Quality of Life

•Sopravvivenza libera da progressione Endpoint(s) secondari •Sopravvivenza generale •Tasso di risposta globale determinato dalla valutazione radiologica secondo i criteri RECIST (Response Evaluation Criteria in Solid Tumors) •Beneficio clinico (CR, PR o SD per 6 mesi) •Tempo alla risposta •Tempo alla progressione •Durata della risposta •Qualita` della vita

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.6

Cross over

Yes

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

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-02-17.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	10
F.4.2	For a multinational trial
F.4.2.1	In the EEA	30
F.4.2.2	In the whole clinical trial	270

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

2006-02-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-12-15

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials