A Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
A Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth
 factor receptor 2 (HER2)-positive metastatic breast cancer.
Inclusion Criteria:

 -  Signed study-specific Informed Consent Form(s)

 -  Age ≥ 18 years

 -  Histologically documented breast cancer

 -  HER2-positive disease

 -  Metastatic breast cancer

 -  Disease progression on the last chemotherapy regimen received in the metastatic
 setting

 -  Prior treatment with an anthracycline, trastuzumab, a taxane, lapatinib, and
 capecitabine in the neoadjuvant, adjuvant, locally advanced, or metastatic setting and
 prior treatment with at least two lines of therapy (a line of therapy can be a
 combination of two agents or single-agent chemotherapy) in the metastatic setting

 -  At least two lines of anti-HER2 therapy must have been given in the metastatic setting
 as monotherapy or combined with chemotherapy or hormonal therapy. The HER2-targeted
 agent can include trastuzumab, lapatinib, or an investigational agent with
 HER2-inhibitory activity.

 -  A minimum of 6 weeks of trastuzumab for the treatment of metastatic disease is
 required

 -  Patients must have had at least 14 days of exposure in the metastatic setting to
 lapatinib and capecitabine (given together or separately) unless they were intolerant
 of lapatinib and/or capecitabine

 Exclusion Criteria:

 -  Chemotherapy ≤ 21 days before enrollment

 -  Trastuzumab ≤ 21 days before enrollment

 -  Hormone therapy ≤ 7 days before enrollment

 -  Granulocyte-stimulating agent < 14 days before enrollment

 -  Investigational therapy ≤ 28 days before enrollment

 -  Previous radiotherapy for treatment of metastatic breast cancer ≤ 21 days before
 enrollment

 -  Brain metastases that are untreated, symptomatic, or require therapy to control
 symptoms; or any radiation, surgery, or other therapy to control symptoms from brain
 metastases within 3 months of the first study treatment

 -  History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to
 trastuzumab or murine proteins

 -  History of exposure to the following cumulative doses of anthracyclines: Doxorubicin
 or liposomal doxorubicin > 500 mg/m^2; Epirubicin > 900 mg/m^2; Mitoxantrone > 120
 mg/m^2 and idarubicin > 90 mg/m^2

 -  Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology
 Criteria for Adverse Events (NCI CTCAE), v3.0

 -  History of other malignancy within the last 5 years, except for carcinoma in situ of
 the cervix or basal cell carcinoma

 -  Current unstable angina

 -  History of symptomatic congestive heart failure (CHF), or ventricular arrhythmia
 requiring treatment

 -  History of myocardial infarction within 6 months of enrollment

 -  Left ventricular ejection fraction (LVEF) < 50% within 28 days of enrollment

 -  History of decreased LVEF to < 50% or symptomatic CHF with previous adjuvant
 trastuzumab treatment

 -  Severe dyspnea at rest due to complications of advanced malignancy or requiring
 current continuous oxygen therapy

 -  Current severe, uncontrolled systemic disease (e.g., clinically significant
 cardiovascular, pulmonary, or metabolic disease)

 -  Major surgical procedure or significant traumatic injury within 28 days before
 enrollment or anticipation of the need for major surgery during the course of study
 treatment

 -  Current pregnancy or lactation

 -  Current known infection with human immunodeficiency virus (HIV), active hepatitis B,
 and/or hepatitis C virus

 -  Assessed by the investigator to be unable or unwilling to comply with the requirements
 of the protocol