Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	18 and over	Pharmaceutical / Industry	EGF106903 BIG 1-06, NCT00553358

Trial Description

Summary

This is a randomised, open label multicenter Phase III study comparing the efficacy of neoadjuvant lapatinib plus paclitaxel, versus trastuzumab plus paclitaxel, versus concomitant lapatinib and trastuzumab plus paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer. Patients will be randomised to receive either: lapatinib 1500 mg daily, trastuzumab 4 mg/kg iv load followed by 2 mg/kg iv weekly, or lapatinib 1000 mg daily with trastuzumab 4 mg/kg iv load followed by 2 mg/kg iv weekly for a total of 6 weeks. After this biological window, patients will continue on the same targeted therapy plus weekly paclitaxel 80 mg/m2 for a further 12 weeks, up to definitive surgery. After surgery, patients will receive three courses of adjuvant chemotherapy with FEC followed by the same targeted therapy as in the neoadjuvant setting for a further 34 weeks. The planned total duration of the anti-HER2 therapy will be one year. The primary objective of this study is to evaluate and compare the rate of pathological complete response at the time of surgery in patients randomised to receive neoadjuvant lapatinib or trastuzumab or their combination plus paclitaxel. Secondary objectives include the comparisons of safety and tolerability, objective tumour response rate, disease free survival and overall survival, conversion to breast conserving surgery and node negative disease at surgery among the three neoadjuvant treatment arms and the identification of molecular features of responding tumours.

Eligibility Criteria

Inclusion Criteria:

• Female gender;

• Age ≥18 years;

• Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 (See Appendix 2 );

• Histologically confirmed invasive breast cancer:

• Primary tumour greater than 2 cm diameter, measured by clinical examination and mammography or echography,

• Any N,

• No evidence of metastasis (M0) (isolated supraclavicular node involvement allowed);

• Over expression and/or amplification of HER2 in the invasive component of the primary tumour [Wolff et al 2006] and confirmed by a certified laboratory prior to randomisation

• Known hormone receptor status.

• Haematopoietic status:

• Absolute neutrophil count > 1,5 x 10^9/L,

• Platelet count > 100 x 10^9/L,

• Hemoglobin at least 9 g/dl,

• Hepatic status:

• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 2 x ULN) is allowed,

• AST and ALT ≤ 2.5 times ULN,

• Alkaline phosphatase ≤ 2.5 times ULN,

• Renal status:

• Creatinine ≤ 2.0 mg/dL,

• Cardiovascular:

• Baseline LVEF ³ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,

• Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential)

• Fertile patients must use effective contraception (barrier method - condoms, diaphragm
• also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed)

• Signed informed consent form (ICF)

• Patient accepts to make available tumour samples for submission to central laboratory to conduct translational studies as part of this protocol

Exclusion Criteria:

• Received any prior treatment for primary invasive breast cancer;

• Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated:

• Basal and squamous cell carcinoma of the skin;

• Carcinoma in situ of the cervix. Patients with a prior malignancy diagnosed more than 10 years prior to randomisation may enter the study. Patients must have been curatively treated with surgery alone. Radiation therapy or systemic therapy (chemotherapy or endocrine) are NOT permitted. Prior diagnoses of breast cancer or melanoma are excluded.

• Diagnosis of inflammatory breast cancer;

• Bilateral cancer;

• This criterion has been deleted from the protocol Version 1. Patients with multi-focal cancer are no longer excluded.

• Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, uncontrolled hypertension (= 180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen;

• 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;

• Unresolved or unstable, serious adverse events from prior administration of another investigational drug; 9) Active or uncontrolled infection;

• Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;

• Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies);

• Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients;

• Pregnant or lactating women;

• Concomitant use of CYP3A4 inhibitors or inducers

• Concomitant use of CYP3A4 inhibitors or inducers

Trial Contact Information

Trial Lead Organizations/Sponsors

GlaxoSmithkline

GSK Clinical Trials, MD

Study Director

US GSK Clinical Trials Call Center

Ph: 877-379-3718

Argentina
Buenos Aires
	Ciudad Autonoma de Buenos Aires
	GSK Investigational Site
Belgium
	Bruxelles
	GSK Investigational Site
	Leuven
	GSK Investigational Site
	Namur
	GSK Investigational Site
Canada
Quebec
	Montreal
	GSK Investigational Site
Czech Republic
	Brno
	GSK Investigational Site
	Novy Jicin
	GSK Investigational Site
France
	Villejuif Cedex
	GSK Investigational Site
Hong Kong
	Hong Kong
	GSK Investigational Site
	Wanchai
	GSK Investigational Site
India
	New Delhi
	GSK Investigational Site
	Pune
	GSK Investigational Site
Italy
	genova
	GSK Investigational Site
	Genova
	GSK Investigational Site
Lithuania
	Vilnius
	GSK Investigational Site
Peru
	Lima
	GSK Investigational Site
Republic of Korea
	Seoul
	GSK Investigational Site
	songpa-gu, Seoul
	GSK Investigational Site
Republic of South Africa
	Pretoria
	GSK Investigational Site
Romania
	Bucuresti
	GSK Investigational Site
Russia
	Moscow
	GSK Investigational Site
	Ryazan
	GSK Investigational Site
	St. Petersburg
	GSK Investigational Site
Spain
	Barcelona
	GSK Investigational Site
	Madrid
	GSK Investigational Site
Sweden
	Göteborg
	GSK Investigational Site
Taiwan, Province of China
	Taipei
	GSK Investigational Site
Ukraine
	Dnipropetrovsk
	GSK Investigational Site
	Sympheropol
	GSK Investigational Site
United Kingdom
	Bournemouth
	GSK Investigational Site
	London
	GSK Investigational Site

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00553358
Information obtained from ClinicalTrials.gov on March 18, 2009