Health Condition 1: null- Breast cancer.
Conditions
Interventions
Intervention1: Drug: Lapatinib: Design-1: Arm-2 &
3 has 1500mg daily Lapatinib for 52 &
34 wks respectively and arm-4 has 1000mg for 52 wks.
In Design-2:
Treatment Arm 2: weekly paclitaxel 80mg/m2 IV for 12 doses OR three weekly docetaxel* 75 mg/m2 IV for 4 cycles over 12 weeks concomit
Sponsors
GlaxoSmithKline Pharmaceuticals Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1)Age 18 years and above. 2)Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1; 3)Non-metastatic operable primary invasive adenocarcinoma of the breast fulfilling the following: (a) Histologically confirmed; (b) Adequately excised (exceptions: patients who have â??non-resectableâ?? deep margin invasion are eligible provided they have had or will receive radiotherapy encompassing the region concerned; patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumour bed); (c) Axilla dissected; sentinel node sampling is allowed, provided that axillary dissection follows confirmation of a positive sentinel node; sentinel node sampling alone is NOT acceptable after neoadjuvant chemotherapy (in patients receiving neoadjuvant chemotherapy lymph node status will be considered unknown, regardless of the results of post-chemotherapy axillary dissection); (d) Axillary node positive patient OR node negative patient with a tumour greater than or equal to 1.0 cm in greatest diameter. For clarification, isolated tumour cells (ITC) are considered pN0 and micrometastases are considered pN1. 4) Known hormone receptor status (ER/PgR or ER alone); 5) For Designs 1 and 2: Patient must have received at least four cycles of an approved anthracycline-based (neo-) adjuvant chemotherapy regimen or listed as an exception in Table 5. For Design 1: Randomisation must be performed no longer than 12 weeks from Day 1 of the last chemotherapy cycle after obtaining a post-chemotherapy LVEF more than or equal to 50. Study treatment must start no more than 14 days after randomisation. For Design 2: Randomisation must be performed no longer than 6 weeks from Day 1 of the last anthracycline-containing chemotherapy cycle after obtaining a post-anthracycline chemotherapy LVEF more than or equal to 50. Study treatment must start no more than 14 days after randomisation and must be concurrent with taxanes. For Design 2B: Randomisation must be performed no longer than 8 weeks from definitive surgery. Non-anthracycline platinum containing regimen (docetaxel and carboplatin) and study treatment must start concomitantly and no more than 14 days after randomisation. 6) Baseline LVEF more than or equal to 50% measured by echocardiography or MUGA scan: For Design 1 and Design 2 - after completion of all anthracycline-based (neo-) adjuvant chemotherapy and prior to the targeted therapy(ies); for Design 2B - prior to targeted therapy(ies) and chemotherapy (docetaxel and carboplatin). 7) Over expression and/or amplification of HER2 in the invasive component of the primary tumour (in case of neoadjuvant treatment, tissue sample used for HER2 testing should be collected before neoadjuvant treatment starts), according to one of the following definitions [Wolff, 2007] and confirmed by central laboratory prior to randomisation: -3+ over expression by IHC (more than 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 HER2 gene amplification; -HER2 gene amplification by FISH/CISH (more than 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of more
Exclusion criteria
Exclusion criteria: Patients meeting any ONE of the following criteria are not eligible for this study: 1) History of any prior (ipsi- and/or contralateral) invasive breast carcinoma; 2) Past (less than 10 years) or current history of malignant neoplasms, except for curatively treated 1) basal and squamous cell carcinoma of the skin or 2) carcinoma in situ of the cervix. NOTE: Patients with a prior malignancy diagnosed greater than 10 years in the past who have been curatively treated with surgery ONLY, WITHOUT radiation therapy or systemic therapy (chemotherapy or endocrine) are eligible for the study. Patients with any prior diagnosis of invasive breast cancer or melanoma, at any time, are excluded from this study. 3) Any clinically staged T4 tumour, including inflammatory breast cancer; 4) Bilateral tumours; 5) This exclusion criterion has been removed as of protocol amendment 1. NOTE: multifocal/multicentric tumours are permitted: - If the patient is node-negative: one of the lesions must be equal or greater than 1.0 cm (sum of the lesion diameters is not acceptable) AND must have positive HER2 status centrally-confirmed; - If patient is node-positive: lesion size does not matter BUT one of the lesions must have HER2 positivity centrally-confirmed. If several lesions are found to be HER2 positive locally, the largest lesion should be considered for central review. 6) Maximum cumulative dose of doxorubicin more than 360mg/m2 or maximum cumulative dose of epirubicin more than 720mg/m2 or any prior anthracyclines unrelated to the present breast cancer; 7) (Neo-) or adjuvant chemotherapy using peripheral stem cell or bone marrow stem cell support; 8) Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer; 9) Patients with positive or suspicious internal mammary nodes identified by sentinel node technique, which have not been irradiated or will not be irradiated, or patients with supraclavicular lymph node involvement (confirmed by fine needle aspirate or biopsy); 10) Prior use of anti-HER 2 therapy for any reason or other prior biologic or immunotherapy for breast cancer; 11) Concurrent anti-cancer treatment, except hormonal therapy or radiotherapy for the present breast cancer; 12) Concurrent anti-cancer treatment in another investigational trial with hormone therapy or immunotherapy unless approved by the Executive Committee; 13) Serious cardiac illness or medical conditions including but not confined to: a) History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF less than 50%); b) High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled); c) Angina pectoris requiring antianginal medication; d)Clinically significant valvular heart disease; e) Evidence of transmural infarction on ECG; f) Poorly controlled hypertension (e.g. systolic more than 180mm Hg or diastolic more than 100mm Hg); 14) Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness; 15) Any of the following abnormal laboratory tests immediatel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free survival will be analysed after 1388 events, using a two-sided stratified log-rank test.Timepoint: 1388 events | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival; Time to recurrence; Time to distant recurrence; Incidence of brain metastasesTimepoint: Around 10 years | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Czech Republic, Democratic People's Republic of Korea, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Luxembourg, Malaysia, Mexico, Netherlands, New Zealand, Norway, Pakistan, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactKedar Nayak
GlaxoSmithKline Pharmaceuticals Ltd.
Outcome results
None listed