This phase II trial studies how well carvedilol works in treating heart disease (cardiomyopathy) in patients with breast cancer that is new or has come back at or near the same place as the primary tumor (locally recurrent), who are planning to receive trastuzumab therapy. Carvedilol is a drug used to treat high blood pressure and certain heart problems and may help to treat heart disease in patients with breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03879629.
PRIMARY OBJECTIVE:
I. To compare a pre-emptive approach and a reactive preventive approach with a “wait-and-see strategy” of carvedilol initiation to address the question of if and when to start cardioprotective efforts for patients undergoing trastuzumab +/- pertuzumab or trastuzumab-emtansine (TDM1) (here-forth referred to collectively as “HER2-directed therapy” or “anti-HER2” therapy unless specified individually).
SECONDARY OBJECTIVES:
I. To compare a pre-emptive approach and a reactive preventive approach with current approach by evaluating reversible left ventricular ejection fraction (LVEF) decline to within 5% of baseline
II. To compare the delta change in LVEF from completion to one year after completion of HER2-directed therapy between a cardioprotective approach with carvedilol confined to the duration of HER2-directed therapy or extended for one year thereafter.
EXPLORATORY OBJECTIVE:
I. To test the association of predefined genetic variants with change in global longitudinal strain (GLS) and LVEF during and after HER2-directed therapy, adjusted for treatment arm.
OUTLINE: Patients are randomized to 1 of 3 groups.
GROUP I (PRE-EMPTIVE STRATEGY): Patients receive carvedilol orally (PO) twice daily (BID) prior to initiation of HER2-directed therapy until the completion of HER2-directed therapy or for an additional year.
GROUP II (REACTIVE STRATEGY): Patients receive carvedilol PO BID during HER2-directed therapy if any of the three monthly heart tests show either an elevation in cardiac troponin or abnormal GLS until the completion of HER2-directed therapy or for an additional year.
GROUP III (REFERENCE STRATEGY): Patients receive carvedilol PO BID after a decline in LVEF by > 10% in patients whose LVEF is >= 50% or LVEF drop >= 5% in those with a decrease to < 50% until the completion of HER2-directed therapy or for an additional year.
After completion of study treatment, patients are followed up at 6 and 12 months post HER2-directed therapy.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationMayo Clinic in Rochester
Principal InvestigatorJoerg Herrmann
