Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer

A Phase 2, Multicenter, Single-Arm Study of Eribulin Mesylate With Trastuzumab as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Positive Breast Cancer

This is a multicenter phase 2 study designed to evaluate the safety and efficacy of eribulin mesylate in combination with trastuzumab as first line treatment in female subjects with locally recurrent or metastatic human epidermal growth factor receptor (HER2) positive breast cancer.

Key Inclusion criteria:

• Age 18 years or older
• Histologically or cytologically proven adenocarcinoma of the breast
• Subjects who have locally recurrent or metastatic disease with at least one measurable lesion
• HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0, 1 or 2
• At least 12 months since prior neoadjuvant or adjuvant chemotherapy
• At least 2 weeks since prior radiotherapy, endocrine therapy, trastuzumab, or lapatinib, with complete recovery from the effects of these interventions
• Adequate renal function
• Adequate bone marrow function
• Adequate liver function
• Adequate cardiac function

Key Exclusion criteria:

• Prior chemotherapy, biologic therapy, or investigational therapy for locally recurrent or metastatic HER2 breast cancer.
• Subjects who have had a prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer
• Prior exposure to greater than 360 mg/m2 doxorubicin or liposomal doxorubicin, greater than 120 mg/m2 mitoxantrone, greater than 90 mg/m2 idarubicin, or greater than 720 mg/m2 epirubicin
• Inflammatory breast cancer
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Clinically significant cardiovascular impairment
• Subjects with known central nervous system (CNS) disease are not eligible, except for those subjects with treated brain metastasis.
• Subjects with metastatic disease limited to bone are ineligible unless there is at least one lytic lesion with identifiable soft tissue components that can be evaluated by computed tomography (CT) or magnetic resonance imaging (MRI)
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen
• History of bleeding diasthesis
• Currently pregnant or breast-feeding.
• Subjects with preexisting Grade 3 or 4 neuropathy. Any peripheral neuropathy must recover to Grade less than or equal to 2 before enrollment