Cardiac Safety Study in Patients With HER2 + Breast Cancer
Condition: HER2 Positive Breast Cancer; Left Ventricular Function Systolic Dysfunction
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab; Pertuzumab; Ado Trastuzumab Emtansine
Intervention description: HER2 therapy; HER2 therapy; HER2 therapy
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: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: Breast Cancer HER2 Positive; Cardiac Safety

Summary:

      HER2 positive breast cancer cells have more HER2 receptor (a protein on the surface of cells)
      than normal breast cells. Approximately 30% of patients with breast cancer have HER2 positive
      breast cancer. Before HER2 targeted therapies (i.e. treatments that directly block the
      receptor HER2) were developed, patients with HER2 positive breast cancer had a very
      aggressive form of disease. With the use of trastuzumab, an anticancer drug that directly
      targets the receptor HER2, and more recently, pertuzumab and ado-trastuzumab emtansine,
      patients are able to live longer and have better control of their cancer.

      Unfortunately the use of HER2 targeted therapies can increase the risk of heart problems and
      for this reason these treatments were only studied and approved for patients with normal
      heart function.

      In this study we plan to give HER2 targeted therapies to patients with HER2 positive breast
      cancer and mildly decreased heart function along with concomitant evaluation by a heart
      doctor (called cardiologist) and appropriate medications to strengthen the heart. We will do
      frequent monitoring of the heart function with a test called echocardiogram that will give us
      a detailed "picture" of the heart. We will also draw blood along with routine blood tests to
      try to understand why some patients develop heart problems and others do not. The study will
      take a maximum of 12 months and patients will be monitored for 6 additional months.

      We hypothesize that it is safe to administer HER2 targeted therapies to patients with breast
      cancer and mildly decreased heart function, i.e. LVEF between 40 and 50%, while on
      appropriate heart medications.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female or male patient diagnosed with stage I-IV breast cancer

          -  HER2 positive breast cancer, defined by immunohistochemical staining for HER2 protein
             of 3+ intensity and/or amplification of the HER2 gene on fluorescence in situ
             hybridization (FISH) ≥ 2.0 on breast specimen or biopsy of a metastatic site

          -  LVEF < 50% and ≥ 40% documented in echocardiogram done within the last 30 days

          -  HER2 therapy naïve or currently receiving non-lapatinib HER2 targeted therapy

          -  Patient receiving or planning to receive trastuzumab, trastuzumab with pertuzumab or
             ado-trastuzumab emtansine, for at least 3 months, alone or in combination with other
             systemic treatment or radiation

          -  Age ≥ 18 years

          -  Patient is willing and able to comply with protocol required assessments and
             procedures

        Exclusion Criteria:

          -  Previous hospitalization due to documented heart failure in the last 12 months

          -  Current signs or symptoms of heart failure or ischemia

          -  History of arrhythmia requiring pharmacological or electrical treatment

          -  Concomitant use of anthracyclines or use of anthracyclines in the last 50 days

          -  Pregnant or lactating patients. Patients of childbearing potential must implement
             contraceptive measures during study treatment and for 7 months after last dose of
             treatment drug and must have negative urine or serum pregnancy test within 7 days
             prior to registration.

          -  History of significant neurologic or psychiatric disorders including psychotic
             disorders or dementia that would prohibit the understanding and giving of informed
             consent.