Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer (BOLERO-3)

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• HER2+ status defined as IHC 3+ staining or in situ hybridization positive
• Patients with resistance to trastuzumab
• Prior taxane therapy
• Patients with an ECOG performance status of 0 - 2
• Patients with measurable disease as per RECIST criteria
• Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
• Patients must meet laboratory criteria defined in the study within 21 days prior to randomization

Exclusion Criteria:

• Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
• More than three prior chemotherapy lines for advanced disease.
• Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Peripheral neuropathy ≥ grade 2 at randomization
• Active cardiac disease
• History of cardiac dysfunction
• Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
• Known hypersensitivity to any study medication
• Breastfeeding or pregnant

Other protocol-defined inclusion/exclusion criteria may ap