A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer Who Have Received Prior Anti-HER2 And Chemotherapy-based Treatment
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab Emtansine
Intervention description: Participants will receive trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenously on Day 1 of a 3-week cycle every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2185.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This two-cohort, open-label, multicenter study will assess the safety, efficacy and
      tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced
      breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and
      chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general
      participant population; Cohort 2 will include only Asian participants.
    

Eligibility criteria:

        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, LABC, or mBC, defined by the
             investigator: progression must occur during or after most recent treatment for
             LABC/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

          -  Use of highly effective contraception as defined by the protocol

        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 National Cancer Institute (NCI) common
             terminology criteria for adverse events (CTCAE) v 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

          -  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 participant
             must have recovered from any resulting acute toxicity (to Grade </=1) prior to first
             study treatment.

          -  Metastatic central nervous system (CNS) disease only

          -  Brain metastases which are symptomatic

          -  History of a decrease in LVEF to less than (<) 40% or symptomatic congestive heart
             failure (CHF) with previous trastuzumab treatment

          -  History of symptomatic 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 (clinically significant cardiovascular,
             pulmonary, or metabolic disease)

          -  Pregnancy or lactation

          -  Currently known active infection with human immunodeficiency virus (HIV), hepatitis B
             virus, or hepatitis C virus

          -  History of intolerance (such as Grade 3-4 infusion reaction) or hypersensitivity to
             trastuzumab or murine proteins or any component of the product