Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trastuzumab or lapatinib ditosylate is more effective in treating women with early breast cancer.
PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works compared with lapatinib ditosylate in treating women with early breast cancer.
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Perioperative AntiHER-2 Therapy on Early Breast Cancer Study - Biological Phase (EPHOS-B)|
- Increase in apoptosis, by change in the tumor (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery (biological phase) [ Designated as safety issue: No ]
- Fall in proliferation between diagnosis and surgery by change in proliferation measured by Ki67 immunohistochemical assessment (%) at diagnosis and at surgery (biological phase) [ Designated as safety issue: No ]
- Relapse-free survival (clinical phase) [ Designated as safety issue: No ]
- Changes in the angiogenic serum markers VEGF-A, VEGF R1, and CD105, measured at diagnosis, surgery (plus also tumor CD31) and 28-30 days post surgery (biological phase) [ Designated as safety issue: No ]
- Pre-treatment and/or surgical expression of molecular markers (EGFR, Her-3, IGF1R, c-myc, AKT, p-ERK, pS6 inase, activated src, or truncated p95HER-2 expression) [ Designated as safety issue: No ]
- Time to local recurrence (clinical phase) [ Designated as safety issue: No ]
- Time to distant recurrence (clinical phase) [ Designated as safety issue: No ]
- Overall survival (clinical phase) [ Designated as safety issue: No ]
|Study Start Date:||April 2010|
|Estimated Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
- 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.
- 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
|Manchester, England, United Kingdom, M23 9LJ|
|Contact: Contact Person 44-208-722-4154 Nigel.email@example.com|
|Principal Investigator:||Nigel Bundred||Wythenshawe Hospital|