Clinical Trials Register

Summary
EudraCT Number:	2010-018389-22
Sponsor's Protocol Code Number:	LAP113957
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-11-05
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2010-018389-22

A.3

Full title of the trial

A randomized, multicentre, open-label, Phase II study of the efficacy and safety of lapatinib plus epirubicin and cyclophosphamide (EC90-L) followed by weekly paclitaxel and lapatinib (PX-L) compared with EC90 followed by weekly paclitaxel and trastuzumab (PX-T), as neoadjuvant therapy in patients with previously untreated ErbB2-overexpressing Stage I - IIIA invasive breast cancer with primary tumour size > 1cm.

A.3.2

Name or abbreviated title of the trial where available

ELATE

A.4.1

Sponsor's protocol code number

LAP113957

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research & 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	Yes
D.2.1.1.1	Trade name	TYVERB
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXOSMITHKLINE 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	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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.3.9.1	CAS number	GW572016
D.3.9.2	Current sponsor code	388082-78-8
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	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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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 injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	anticorpo monoclonale umano

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 previously untreated ErbB2-overexpressing Stage I - IIIA invasive breast cancer with primary tumour size > 1cm.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10006187

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 compare the rate of pathologic response (pCR)in the breast at the time of definitive surgery.

E.2.2

Secondary objectives of the trial

-the pCR rate in the breast and axilla at the time of definite surgery in the study treatment regimen versus the reference regimen; -overall response rate (complete plus partial response) in the breast and axilla; -brest conservation rate

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed written informed consent approved by an Independent Ethics Committee (IEC) and obtained prior to any study specific screening procedures. 2. Female patients aged ≥18 years. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 –1. 4. Histologically confirmed, previously untreated, operable Stage I-IIIA invasive breast cancer: • Primary tumour greater than 1 cm in diameter measured by clinical examination and confirmed by at least one imaging study (mammography, breast ultrasound or MRI). • In the case of a multifocal tumour (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be >1 cm and is designated as the “target” lesion for all subsequent tumour evaluations. 5. Over expression and/or amplification of ErbB2 in the invasive component of the primary tumour according to one of the following definitions. Central laboratory confirmation is not required prior to randomization, but tumour samples must be available for banking and retrospective confirmation. • 3+ over expression by IHC (>30% of invasive tumour cells); • 2+ or 3+ (in 30% or less neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating ErbB2 gene amplification; • ErbB2 gene amplification by FISH/CISH (>6 ErbB2 gene copies per nucleus, or a FISH ratio [ErbB2 gene copies to chromosome 17 signals] of >2.2.) Patients with a negative or equivocal overall result (FISH test ratio of ≤2.2, ≤6.0 ErbB2 gene copies per nucleus) and staining scores of 0,1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are NOT eligible for participation in the trial. 6. Known ER and PgR hormone receptor status. 7. LVEF within institutional normal range (evaluated by multiple-gated acquisition [MUGA] or echocardiography). 8. Women of childbearing potential must have a negative serum pregnancy test within 14 days (preferably 7 days) of first dose of study treatment and agree to use effective contraception, as defined in Section 7.3.2, during the study and for 28 days following the last dose of study drug. 9. Adequate baseline organ function defined by: • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, • Hemoglobin ≥ 9 g/dL, • Platelet count ≥ 100 x 109/L, • Serum bilirubin ≤1.5 x ULN. In the case of known Gilbert´s syndrome, < 2x ULN is allowed, • ALT and AST ≤ 2.5 x ULN, • Alkaline phosphatase ≤ 2.5 x ULN, • Serum creatinine ≤ 1.6 mg/dL or calculated creatinine (Cockcroft and Gault)clearance ≥50mL/m. 10. Patient agrees to make available tumour tissue samples for submission to the central laboratory for planned as well as future translational research. 11. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

E.4

Principal exclusion criteria

1. Metastatic, locally advanced, or inflammatory breast cancer as defined by the AJCC (7th Edition). 2. Bilateral breast cancer. 3. Multicentric breast cancer (defined as the presence of two or more foci of cancer in different quadrants of the same breast). 4. Any prior treatment for primary breast cancer (other than excision of tumour in the contralateral breast, and provided that the patient did not previously receive adjuvant radiotherapy or chemotherapy, all of which exclude the patient). 5. Concurrent participation in another clinical trial involving anti-cancer investigational drug or administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment. 6. History of any prior malignancy in previous 5 years (patients with a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ of the cervix are eligible). 7. History of significant comorbidities that interfere with the conduct of the study, or evaluation of the results, or with informed consent. 8. Active infection. 9. Peptic ulcer or unstable diabetes mellitus within 8 weeks prior to study enrolment. 10. Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular accident (≤6 months before enrolment), myocardial infarction (≤6 months before enrolment), unstable angina, New York Heart Association (NYHA) ≥ grade 2 congestive heart failure, serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment, or not controlled by medication. 11. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert`s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment). 12. Lactating women. 13. Subjects unable to swallow and retain orally administered medication or with any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome, major resection of the stomach or bowels, or ulcerative colitis are also excluded. 14. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator. 15. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to any of the study drugs, active ingredients, or excipients that contraindicates their participation. 16. Concomitant use of CYP3A4 inhibitors or inducers (see Section 6.2 for list of prohibited medications).

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the pathologic complete response (pCR) in the breast at the time of definitive surgery defined as the absence of invasive disease.

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)

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

Yes

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.8.2.3.1

Comparator description

Herceptin/trastuzumab

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

Information not present in EudraCT

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

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

Ultima visita ultimo paziente

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.1.3

Elderly (>=65 years)

Yes

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

129

F.4.2.2

In the whole clinical trial

164

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)

Dopo l`intervento chirurgico definitivo al carcinoma mammario e la visita di follow up, lo studio sara` completato. Dopo la fine dello studio, trattamenti addizionali saranno somministrati secondo gli standard locali a giudizio dello sperimentatore, fra cui radiazioni, terapie addizionali come trastuzumab e terapia ormonale. I costi di questi trattamenti aggiuntivi non sono pagati o rimborsati dallo studio.

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

2010-11-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2011-01-20

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