NCT01104571

Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer

Effect of Perioperative AntiHER-2 Therapy on Early Breast Cancer Study - Biological Phase (EPHOS-B)

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 257 (actual)
• Sponsor: Institute of Cancer Research, United Kingdom · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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. Update June 2013: Since the initial development of EPHOS-B in 2007 more evidence in relation to safety and efficacy of anti-HER2 therapies are now available, and in particular, a growing body of evidence that combinations of two anti-HER2 therapies are more effective than monotherapies. Therefore this study has been amended (PART 2) to a 1:1:2 ratio to control, perioperative trastuzumab or the combination of lapatinib and trastuzumab. PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works compared with lapatinib ditosylate (and in since June 2013 - compared with a combination of lapatinib and trastuzumab) in treating women with early breast cancer.

Detailed description

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 the effects of trastuzumab (Herceptin®), lapatinib ditosylate and the combination of lapatinib ditosylate and trastuzumab (Herceptin®) on the inhibition of proliferation or increase of apoptosis Secondary * To determine whether pre-operative anti-HER2 treatment reduces serum angiogenic factors. * To identify molecular predictors of biological response to anti-HER2 therapy OUTLINE: This is a multicenter study.Patients are stratified according to center. Patients are randomized to 1 of 3 treatment arms. PART 1: From Protocol versions 1 to 4: * 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. PART 2: From Protocol Version 5 (June 2013) * 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 and (trastuzumab \[Herceptin®\] combination): Patients receive 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 neoadjuvant trastuzumab IV over 90 minutes on days 1 and 8 and receive adjuvant trastuzumab on day 15. PART 1 and 2: 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 by Cancer Research UK

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	trastuzumab	Trastuzumab 6mg/kg iv given on days 1 \& 8 pre-surgery \& one dose of 2mg/kg iv between days 15-19 post surgery
DRUG	lapatinib ditosylate	Part 1: Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery. Part 2: Lapatinib 1000mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery.
OTHER	laboratory biomarker analysis
PROCEDURE	adjuvant therapy
PROCEDURE	neoadjuvant therapy
PROCEDURE	therapeutic conventional surgery	therapeutic conventional surgery

Timeline

• Start date: 2010-04-01
• Primary completion: 2017-08-30
• Completion: 2025-09-01
• First posted: 2010-04-15
• Last updated: 2018-09-17

Locations

1 site across 1 country: United Kingdom