A Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab emtansine [Kadcyla]
Intervention description: Intravenous repeating dose
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2-positive breast cancer; HER2; MBC; Trastuzumab emtansine

Summary:

      Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth
      factor receptor 2 (HER2)-positive metastatic breast cancer.
    

Eligibility criteria:

        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