A Multicenter, Single Arm Study of Trastuzumab Emtansine (T-DM1) in HER2 Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-based Treatment.
Inclusion Criteria:
- HER2-positive disease determined locally
- Histologically or cytologically confirmed invasive breast cancer
- Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced or
metastatic setting must include both chemotherapy, alone or in combination with
another agent, and an anti-HER2 agent, alone or in combination with another agent
- Documented progression of incurable, unresectable, locally advanced, or metastatic
breast cancer (mBC), defined by the investigator: progression must occur during or
after most recent treatment for locally advanced/mBC or within 6 months of completing
adjuvant therapy
- Measurable and/or non-measurable disease
- Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram (ECHO) or
multiple-gated acquisition scan (MUGA)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
- Adequate organ function
Exclusion Criteria:
- History of treatment with trastuzumab emtansine
- Prior enrollment into a clinical study containing trastuzumab emtansine regardless of
having received trastuzumab emtansine or not
- Peripheral neuropathy of Grade >/= 3 per NCI CTCAE Version 4.0
- History of other malignancy within the previous 5 years, except for appropriately
treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine
cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers
with a similar curative outcome as those mentioned above
- History of receiving any anti-cancer drug/biologic or investigational treatment
within 21 days prior to first study treatment except hormone therapy, which can be
given up to 7 days prior to first study treatment; recovery of treatment-related
toxicity consistent with other eligibility criteria
- History of exposure to cumulative doses of anthracyclines
- History of radiation therapy within 14 days of first study treatment. The patient
must have recovered from any resulting acute toxicity (to Grade =1) prior to first
study treatment.
- CNS only disease
- Brain metastases which are symptomatic
- History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab
treatment
- History of symptomatic congestive heart failure (CHF; New York Heart Association
[NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment
- History of myocardial infarction or unstable angina within 6 months of first study
treatment
- Current dyspnea at rest due to complications of advanced malignancy or requirement
for continuous oxygen therapy
- Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease)
- Currently known active infection with HIV, hepatitis B virus, or hepatitis C virus