Lisinopril or Carvedilol Phosphate in Reducing Side Effects in Women with HER2-Positive Breast Cancer Receiving Trastuzumab

PRIMARY OBJECTIVES:

I. Determine if administration of lisinopril or carvedilol phosphate extended-release (compared to placebo) will reduce the incidence of trastuzumab-induced cardiotoxicity, as measured by LVEF, in women receiving adjuvant or neoadjuvant trastuzumab for HER2-positive breast cancer.

SECONDARY OBJECTIVES:

I. Determine whether patients randomized to receive lisinopril or carvedilol phosphate extended-release have fewer interruptions in trastuzumab therapy due to cardiomyopathy.

II. Determine changes in quality of life (QOL) in patients treated with these regimens.

III. Determine the long-term effects of lisinopril and/or carvedilol phosphate extended-release on the prevention of cardiomyopathy and their impact on QOL.

IV. Compare the predictive value of troponin I and BNP in the identification of trastuzumab-induced cardiotoxicity.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive oral lisinopril once daily.

ARM II: Patients receive oral carvedilol phosphate extended-release once daily.

ARM III: Patients receive oral placebo once daily.

In all arms, study treatment begins with the first dose of trastuzumab and continues for up to 52 weeks or until the end of trastuzumab therapy.

Quality of life is assessed using the EORTC QLQ-C30 questionnaire at baseline, at 52 weeks (or at the end of trastuzumab therapy), and at 18 and 24 months (or 6 and 12 months after the completion of trastuzumab).

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.