Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab
Condition: Breast Cancer; Cardiac Toxicity
MeSH terms: Breast Neoplasms; Cardiotoxicity
Intervention: Coreg CR®; lisinopril; placebo
Intervention description: Given orally; Given orally; Given orally
Intervention MeSH terms: Carvedilol; Lisinopril
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 468.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cardiac toxicity; HER2-positive breast cancer; recurrent breast cancer; stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; male breast cancer

Summary:

      RATIONALE: Lisinopril or Coreg CR®, may help reduce side effects caused by trastuzumab. It is
      not yet known whether lisinopril or Coreg CR® are more effective than a placebo in reducing
      side effects caused by trastuzumab.

      PURPOSE: This phase II trial is studying lisinopril and Coreg CR® to see how well they work
      compared with a placebo in reducing side effects in patients with HER2-positive breast cancer
      receiving trastuzumab.
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Males and Females ≥ 18 years old diagnosed with HER2 positive breast cancer

          -  Scheduled to receive neoadjuvant or adjuvant trastuzumab (Herceptin®) therapy
             (anthracycline-containing regimens are permitted). Patients receiving Herceptin® with
             their chemotherapy are permitted for eligibility work-up. Taxanes are permitted.
             Trastuzumab (Herceptin®) therapy may be given with or after primary chemotherapy.
             Pertuzumab may be used in conjunction with trastuzumab.

          -  Left Ventricular Ejection Fraction (LVEF) ≥ 50% by MUGA scan or echocardiogram

          -  Adequate renal function for administration of trastuzumab-containing chemotherapy
             regimen.

          -  Sitting systolic blood pressure of > 90 mm Hg

          -  Pulse ≥ 60 beats/minute

          -  Not pregnant or breastfeeding

          -  Female patients of childbearing potential, who are sexually active, must have a
             negative pregnancy test before starting the study

          -  Both men and women must be willing to use effective contraception during the study.
             Teratogenicity is documented for both active study agents

          -  Able to swallow capsules

        EXCLUSION CRITERIA:

          -  Patients with metastatic disease

          -  Prior treatment with trastuzumab or anthracyclines prior to this chemotherapy regimen

          -  Current treatment with angiotensin converting enzyme (ACE) inhibitors, angiotensin
             receptor blockers (ARBs), such as losartan, β-blockers or digoxin

          -  Known cardiac history: heart failure, myocardial infarction, radiation-induced cardiac
             dysfunction

          -  Known allergy to either ACE inhibitors or β-blockers

          -  History of bronchial asthma or related bronchospastic conditions

          -  Hereditary or idiopathic angioedema

          -  History of severe hypersensitivity reactions to drugs or other causes, i.e. bee stings

          -  This protocol does not exclude patients who are participating on other investigational
             studies. Refer to the local IRB guidelines.