Clinical Trials Register

Summary
EudraCT Number:	2010-018389-22
Sponsor's Protocol Code Number:	LAP113957 / SOLTI-1001
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-09-13
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

Norway - NOMA

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.4.1

Sponsor's protocol code number

LAP113957 / SOLTI-1001

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	Glaxo Group Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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	388082-78-8
D.3.9.2	Current sponsor code	GW572016
D.3.9.3	Other descriptive name	ditosylate monohydrate
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	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	Herceptin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Regiatration Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Trastuzumab
D.3.4	Pharmaceutical form	Powder for solution for infusion
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.3.9.1	CAS number	18022-69-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
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	Humanised IgG Monolconal Antibody

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	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to compare the rate of pathologic complete 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 definitive surgery in the
study treatment regimen versus the reference regimen.

• Overall response rate (complete plus partial response) in the breast and axilla.

• The breast 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 of this study is 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

Yes

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

Last Subject Last Visit

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)

After definitive breast cancer surgery and a follow-up visit, the study will be completed. Following study completion, additional treatment may be administered according to local standards of care at the discretion of the investigator. This may include radiation therapy or administration of additional therapy, including trastuzumab or hormonal therapy. The costs of these additional treatments are not reimbursed or paid for through the study.

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

2010-10-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-12-21

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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