a study on Breast Cancer
This is a randomised, open label multi-centre phase III study comparing the activity of lapatinib alone versus trastuzumab alone versus trastuzumab followed by lapatinib versus lapatinib concomitantly with trastuzumab in the adjuvant treatment of patients with ErbB2 overexpressing and/or amplified breast cancer. Patients will be enrolled according to one of two design schemas, with Design 2 having two chemotherapy options (Design 2 and 2B), and will be randomised to one of four treatment regimens within each design schema. The primary objective of this study is to compare disease-free survival (DFS) in patients with HER2 overexpressing and/or amplified breast cancer randomised to trastuzumab for one year versus lapatinib for one year versus trastuzumab (12 or 18 weeks, according to assigned design) followed by a six-week treatment-free interval followed by lapatinib (28 or 34 weeks, according to assigned design) versus trastuzumab in combination with lapatinib for one year (52 weeks). Secondary objectives include treatment comparisons with respect to overall survival, time to recurrence, time to distant recurrence, safety and tolerability, incidence of brain metastasis, and analyses conducted separately for cohorts of patients defined by presence or absence of cMyc oncogene amplification, expression level of PTEN and presence or absence of the p95HER2 receptor. On August 18, 2011, the ALTTO Independent Data Monitoring Committee (IDMC) met to review the first planned interim analysis. The IDMC reported that the comparison of lapatinib alone versus trastuzumab alone crossed the futility boundary, indicating that the lapatinib alone arm was unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival (DFS). The IDMC also stated that the other three arms (trastuzumab alone, sequential trastuzumab/lapatinib arm and the combination arm) should continue as planned with no changes.
A Randomised, Multi-centre, Open-label, Phase III Study of Adjuvant Lapatinib, Trastuzumab, Their Sequence and Their Combination in Patients With HER2/ErbB2 Positive Primary Breast Cancer
Neoplasms, Breast Adjuvant ErbB2-overexpressing Early stage breast cancer HER2/neu gene amplified Lapatinib Trastuzumab
Open to people ages 18 years and up
Non-metastatic operable primary invasive adenocarcinoma of the breast fulfilling the following:
For Design 1: Randomization must be performed no longer than 12 weeks from day 1 of the last chemotherapy cycle after obtaining a post-chemotherapy LVEF ≥ 50. Study treatment must start no more than 14 days after randomization For Design 2: Randomization 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 ≥ 50. Study treatment must start no more than 14 days after randomization 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.
HER2 gene amplification by FISH/CISH (> 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of> than 2.2.) Patients with a negative or equivocal overall result (FISH test ratio of ≤ 2.2, ≤ 6.0 HER2 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.
Equivocal local results may be submitted for a final determination by the central laboratory.
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 breast cancer or melanoma, at any time, are excluded from this study.
NOTE: multifocal/multicentric tumours are permitted:
Serious cardiac illness or medical conditions including but not confined to:
History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%);High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block,supraventricular arrhythmias which are not adequately rate-controlled); Angina pectoris requiring antianginal medication; Clinically significant valvular heart disease; Evidence of transmural infarction on ECG; Poorly controlled hypertension (e.g. systolic>180mm Hg or diastolic>100mm Hg);
Any of the following abnormal laboratory tests immediately prior to randomization:
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; alanine amino transferase(ALAT) or aspartate amino transferase (ASAT)>2.5 x ULN; alkaline phosphatase (ALP)> 2.5 x ULN; serum creatinine>2.0 x ULN; total white blood cell count (WBC) <2.5 x 10^9/L;absolute neutrophil count <1.5 x 10^9/L; platelets <100 x 10^9/L.
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