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.

• Conditions: patients with previously untreated ErbB2-overexpressing Stage I - IIIA invasive breast cancer with primary tumour size > 1cm.; MedDRA version: 12.1Level: LLTClassification code 10006187Term: Breast cancer

• Registration Number: EUCTR2010-018389-22-AT
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-03
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 164

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
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

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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: • The pCR rate in the breast and axilla at the time of definitive surgery in the<br>study treatment regimen versus the reference regimen.<br><br>• Overall response rate (complete plus partial response) in the breast and axilla.<br><br>• The breast conservation rate.;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.