Clinical Trials /

Cardiac Safety Study in Patients With HER2 + Breast Cancer

NCT01904903

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Cardiac Safety Study in Patients With <span class="go-doc-concept go-doc-biomarker">HER2</span> + <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Cardiac Safety Study in Patients With HER2 + Breast Cancer
  • Official Title: SAFE-HEaRt: A Pilot Study Assessing the Cardiac SAFEty of HER2 Targeted Therapy in Patients With HER2 Positive Breast Cancer and Reduced Left Ventricular Function
  • Clinical Trial IDs

    NCT ID: NCT01904903

    ORG ID: ML 28685

    Trial Conditions

    HER2 Positive Breast Cancer

    Left Ventricular Function Systolic Dysfunction

    Trial Interventions

    Drug Synonyms Arms
    Trastuzumab, Pertuzumab, Ado-trastuzumab emtansine HER2 targeted therapies, cardiac medications

    Trial Purpose

    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

    Trial Arms

    Name Type Description Interventions
    HER2 targeted therapies, cardiac medications Experimental Cardiac intervention - cardiac assessment that includes baseline study echocardiogram, beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: 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. Trastuzumab, Pertuzumab, Ado-trastuzumab emtansine

    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 nave 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Proportion of patients who complete planned oncologic therapy without the development of a cardiac event or asymptomatic worsening of cardiac function.

    Secondary Outcome Measures

    Median time to development of an event defined as cardiac event or asymptomatic worsening of left ventricular dysfunction, among patients who developed one event.

    Absolute changes in LVEF during HER2 targeted therapy

    HER2 therapy holds attributed to proportion of patients with symptomatic or asymptomatic cardiotoxicity.

    Correlation of global longitudinal myocardial strain with cardiac events and asymptomatic worsening of cardiac function

    Correlation of standard cardiac troponin I and highly sensitive cardiac troponin T with cardiac events and asymptomatic worsening of cardiac function

    Trial Keywords

    Breast Cancer HER2 Positive

    Cardiac Safety