Cardiac Safety Study in Patients With HER2 + Breast Cancer
Condition: HER2 Positive Breast Cancer; Left Ventricular Function Systolic Dysfunction
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Title: A pilot study evaluating the cardiac safety of HER2 targeted therapy (non-lapatinib)
      in patients with HER2 positive breast cancer and reduced left ventricular function Phase:
      Pilot study Study Duration: 4 years with up to 5 additional years of follow up Study
      Center(s): 3 centers will be participating: MedStar Washington Hospital Center (MWHC),
      MedStar Georgetown University Hospital (MGUH) and Memorial Sloan Kettering Cancer Center
      (MSKCC) Primary Objective: To evaluate the cardiac safety of HER2 targeted therapy
      (non-lapatinib) in patients with HER2 positive breast cancer and reduced left ventricular
      ejection fraction (LVEF) when given concomitantly with cardiac treatment.

      Secondary Objectives:

        -  To evaluate time to development of cardiac event or asymptomatic worsening of cardiac
           function

        -  Absolute changes in LVEF

        -  Delays in HER2 therapy attributed to cardiac causes

        -  Correlations between echocardiographic myocardial strain

        -  cTnI and hs-cTnT at baseline and over time with cardiac events and asymptomatic
           worsening of cardiac function Sample size: 30 patients

      Diagnosis and Main Inclusion Criteria:

        -  HER2 positive breast cancer, stage I-IV.

        -  Mildly decreased cardiac function (LVEF between 40 and 49%) prior to or while receiving
           non-lapatinib HER2 targeted therapy

      Cardiac Intervention:

      - Beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses

      Oncology study Products, Doses, Routes, Regimens:

        -  Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every
           3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every
           week.

        -  Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered
           concomitantly with trastuzumab.

        -  Ado-trastuzumab emtansine: 3.6mg/kg IV every three weeks. Note: both trastuzumab and
           pertuzumab may be administered alone or in combination with other systemic or radiation
           therapy.

      Duration of drug administration: Maximum of 12 months.
    

Intervention name(s): Trastuzumab; Pertuzumab; Ado Trastuzumab Emtansine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): HER2 therapy; HER2 therapy; HER2 therapy
Other intervention name(s): Herceptin; Perjeta; Kadcyla
Intervention MeSH terms: Trastuzumab; Pertuzumab; Ado-Trastuzumab Emtansine; Maytansine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Breast Cancer HER2 Positive; Cardiac Safety