Effect of Perioperative AntiHER-2 Therapy on Early Breast Cancer Study - Biological Phase (EPHOS-B)
18 Years
N/A
Female
Breast Cancer
Trial Information
Effect of Perioperative AntiHER-2 Therapy on Early Breast Cancer Study - Biological Phase (EPHOS-B)
OBJECTIVES:
Primary
- To determine whether pre-operative treatment of HER-2 positive breast cancer patients
with anti-HER2 therapy consisting of trastuzumab (Herceptin®) vs lapatinib ditosylate
inhibits proliferation or increases apoptosis.
- To compare trastuzumab (Herceptin®) and lapatinib ditosylate effects on inhibition of
proliferation or increase of apoptosis.
Secondary
- To determine whether pre-operative anti-HER2 treatment reduces serum angiogenic
factors.
OUTLINE: This is a multicenter study. Patients are stratified according to center. Patients
are randomized to 1 of 3 treatment arms.
- Arm I (control): Patients receive no neoadjuvant or adjuvant therapy. Approximately 14
days after randomization, patients undergo either breast-conservation surgery or
mastectomy.
- Arm II (trastuzumab [Herceptin®]): Patients receive neoadjuvant trastuzumab IV over 90
minutes on days 1 and 8. Approximately 11 days after beginning of neoadjuvant therapy,
patients undergo either breast-conservation surgery or mastectomy, and receive adjuvant
trastuzumab on day 15.
- Arm III (lapatinib ditosylate): Patients receive neoadjuvant oral lapatinib ditosylate
once daily on days 1-11. Within 24 hours after completion of neoadjuvant therapy,
patients undergo either breast-conservation surgery or mastectomy, and receive adjuvant
lapatinib ditosylate once daily on days 12-28.
Patients also receive standard adjuvant systemic therapy, including endocrine therapy (for
hormone-sensitive disease) and/or chemotherapy and radiotherapy.
All patients undergo blood and tissue sample collection periodically for biomarker research
studies comprising biomarkers of proliferation, apoptosis, and angiogenesis.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then annually for 10 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Inclusion 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 4 weeks
- Estrogen receptor-negative patients may enter the trial whether or not they have
taken HRT within the past 4 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 2 weeks 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Increase in apoptosis, by change in the tumor (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery (biological phase)
Safety Issue:
No
Principal Investigator
Nigel Bundred
Investigator Role:
Principal Investigator
Investigator Affiliation:
Wythenshawe Hospital
Authority:
Unspecified
Study ID:
CDR0000669882
NCT ID:
NCT01104571
Start Date:
April 2010
Completion Date:
Related Keywords:
- Breast Cancer
- 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
- Breast Neoplasms
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