Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer

• Status: Active, not recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Cancer Research UK; GlaxoSmithKline; Manchester University NHS Foundation Trust; Novartis; University Hospital of South Manchester NHS Foundation Trust; University of Manchester
• Treatments: Estrogens; Lapatinib; Trastuzumab

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