Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms; Disease Progression
Intervention: pertuzumab; Trastuzumab emtansine [Kadcyla]
Intervention description: Intravenous repeating dose; Intravenous repeating dose
Intervention MeSH terms: Trastuzumab; Pertuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MBC; TDM1; Armed Herceptin; Herceptin; Trastuzumab emtansine

Summary:

      This is a multicenter, open-label, single-arm Phase II study designed to evaluate the effect
      of T-DM1 on the duration of corrected QT (QTc) interval in patients with HER2-positive
      locally advanced or metastatic breast cancer and to make preliminary assessments regarding
      the safety, tolerability, and efficacy of combined T-DM1 and pertuzumab in patients with
      early disease progression.

      The QT interval is a measure of time between the start of the Q wave and the end of the T
      wave in the heart's electrical cycle. The QTcF interval is the QT interval as calculated
      using Fridericia's correction; the QTcB interval is the QT interval as calculated using
      Bazett's correction.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically documented, locally advanced, or metastatic breast cancer; measurable
             and/or non-measureable but evaluable disease is permitted

          -  HER2-positive disease

          -  History of prior trastuzumab therapy

          -  Life expectancy ≥ 90 days as assessed by the investigator

          -  Negative urine pregnancy test ≤ 72 hours prior to Cycle 1 Day 1 for all women of
             childbearing potential

          -  For patients of childbearing potential, agreement to use one highly effective form of
             contraception or two effective forms of contraception for the duration of the study
             treatment(s) and for 4 months after the last dose of T-DM1 or 6 months after the last
             dose of pertuzumab, if applicable

        Exclusion Criteria:

          -  Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy
             for the treatment of breast cancer within 2 weeks of the first study treatment

          -  Prior T-DM1 or pertuzumab therapy

          -  History of intolerance (such as Grade 3-4 infusion reaction) and/or adverse events
             related to trastuzumab

          -  Grade ≥ 2 (based on National Cancer Institute Common Terminology Criteria for Adverse
             Events [NCI CTCAE] v3) peripheral neuropathy at the time of or within 3 weeks prior to
             the first study treatment

          -  Brain metastases that are untreated or progressive or have required any type of
             therapy, including radiation, surgery, and/or steroids, to control symptoms from brain
             metastases within 60 days prior to the first study treatment

          -  History of cardiac disease, unstable angina, symptomatic congestive heart failure
             (CHF) (Class ≥ II per the New York Heart Associate [NYHA] guidelines), myocardial
             infarction, or ventricular arrhythmia ≤ 6 months prior to Cycle 1, Day 1

          -  Implantable pacemaker or automatic implantable cardioverter defibrillator

          -  Congenital long QT syndrome or family history of long QT syndrome

          -  Current uncontrolled hypertension

          -  Current treatment with medications that alter cardiac conduction (e.g., digitalis,
             beta-blockers, or calcium channel blockers) or medications that are generally accepted
             to have a risk of causing torsades de pointes (TdP)

          -  Current known active infection with human immunodeficiency virus (HIV), hepatitis B
             virus, or hepatitis C virus

          -  Major surgical procedure or significant traumatic injury within 28 days prior to first
             study treatment, or anticipation of the need for major surgery during the course of
             study treatment