Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer (EPHOS-B)
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring HER2-positive breast cancer, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, estrogen receptor-negative breast cancer, estrogen receptor-positive breast cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed (by core biopsy) invasive breast cancer
- Newly diagnosed disease
- Resectable disease
- HER2-positive disease, defined as 3+ measured by IHC or gene amplification by fluorescent in situ hybridization (FISH)
- No evidence of metastatic disease (T4 category) or suspicion of distant metastases
- No inflammatory breast cancer
- Planned surgery within 1 month of diagnosis, and willing to undergo adjuvant chemotherapy and trastuzumab post-surgery
- Must consent to donation of tissue and blood samples
Hormone receptor status known
- Estrogen receptor-positive patients on hormone replacement therapy (HRT) must either continue HRT or must not have taken HRT within the past 3 weeks
- Estrogen receptor-negative patients may enter the trial whether or not they have taken HRT within the past 3 weeks
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Serum creatinine < 2 times upper limit of normal (ULN) OR creatinine clearance > 30 mg/dL
- Bilirubin < 2 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective non-hormonal contraception
- LVEF ≥ 55% by echocardiography or MUGA
- No clinically significant cardiac abnormalities or uncontrolled hypertension
- No prior myocardial infarction, heart failure, or significant angina
- No prior cancer at any other site that has been treated within the past 6 months (except basal cell carcinoma or cervical carcinoma in situ)
- No current active hepatic or biliary disease (except Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per investigator assessment)
- No impaired gastrointestinal function that would sufficiently reduce lapatinib ditosylate absorption
- No known immediate or delayed hypersensitivity or reaction to drugs chemically related to trastuzumab or lapatinib ditosylate
- No altered mental state that would preclude obtaining written informed consent
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior trastuzumab (Herceptin®) therapy within the past 3 months
- No prior local cancer treatment (e.g., radiotherapy)
- No other concurrent investigational agent or anticancer therapy
- No use of herbal (alternative) therapies within 1 day of study entry (vitamin and/or mineral supplements allowed)
- No regular use of systemic steroids or other agents that could influence study endpoints (inhaled steroids allowed)
- No grapefruit and grapefruit juice for the duration of the study
- At least 14 days since prior and no concurrent CYP3A4 inducers
- At least 7 days since prior and no concurrent CYP3A4 inhibitors
- At least 6 months since prior and no concurrent amiodarone
Sites / Locations
- Wythenshawe Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Other
Experimental
Experimental
Other
Experimental
Experimental
Part 1: Control
Part 1: Trastuzumab
Part 1: lapatinib
Part 2: Control
Part 2: Trastuzumab
Part 2: lapatinib-trastuzumab combination
No peri-operative therapy given
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery
No peri-operative therapy
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.