A Study of the Addition of Metronomic Capecitabine to Standard Adjuvant Therapy in High Risk HER2+ BC paTients

Exclusion Criteria

• •Stage IV (metastatic) breast cancer
• •History of any prior (ipsi- or contralateral) breast cancer except lobular CIS
• •Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery
• •An overall response of PD according to the investigator at the conclusion of preoperative systemic therapy
• •Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment
• •History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with an outcome similar to those mentioned above
• •Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
• •Current NCI CTCAE (Version 4.0) Grade ≥ 2 peripheral neuropathy
• •History of exposure to the following cumulative doses of anthracyclines:
• •Doxorubicin \>240 mg/m2, Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) \>480 mg/m2 For other anthracyclines, exposure equivalent to doxorubicin \>240 mg/m2
• •Cardiopulmonary dysfunction as defined by any of the following:
• •History of NCI CTCAE (Version 4.0) Grade ≥ 3 symptomatic CHF or NYHA criteria Class ≥ II Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate \> 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type 2 \[Mobitz 2\] or third degree AV-block) Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy.
• •History of a decrease in LVEF to \<40% with prior trastuzumab treatment (e.g., during preoperative therapy) Uncontrolled hypertension (systolic blood pressure \>180 mmHg and/or diastolic blood pressure \>100 mmHg) Evidence of transmural infarction on ECG Requirement for continuous oxygen therapy
• •Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers)
• •For female patients, current pregnancy and/or lactation
• •Major surgical procedure unrelated to breast cancer or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• •Any known active liver disease, for example, disease due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis. Patients who have positive HBV or HCV serologies without known active disease must meet the eligibility criteria for ALT, AST, TBILI, INR, aPTT, and alkaline phosphatase (ALK) on at least two consecutive occasions, separated by at least 1 week, within the 30 day screening period.
• •Concurrent, serious, uncontrolled infections or known infection with HIV
• •History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
• •Active, unresolved infections at screening requiring treatment
• •Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol