Prospective Observational Cohort Study of Patients with Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity

Step 1 Registration (reg):

-Pts must have metastatic breast cancer and be initiating within 11 days of Step 1 Reg or continuing trastuzumab�based HER-2 targeted therapy without concurrent anthracyclines and be receiving trastuzumab-based HER-2 targeted therapy for metastatic disease in first, second, third, or fourth line setting.
-Pts may have brain metastasis.
-No limit for # of doses of HER-2 targeted therapy prior to reg.
-Ex) of eligible HER-2 targeted therapy: Trastuzumab, Trastuzumab + chemotherapy or hormonal therapy, Trastuzumab + other HER-2 targeted agent w/ or w/o chemotherapy (such as pertuzumab, lapatinib, and tucatinib), Ado-transtizamab, and Fam-trastuzumab
-Pts on lapatinib w/o trastuzumab are not eligible.
-Planned treatment with concurrent HER-2 targeted therapy and anthracyclines is not permitted.
-Pts must be at increased risk for cardiotoxicity defined by at least 1 of the following:
Previous anthracycline exposure or 1 or more of the following risk factors for heart disease: LVEF 50-54% by local ECHO read, age >/= 65, BMI >/= 30 kg/m2,current or prior anti-hypertensive therapy, dx of coronary artery disease (CAD), diabetes mellitus, atrial fibrillation/flutter.
-Pts must not have taken w/i 21 days prior to Step 1 Registration, be currently taking at the time of Step 1 reg, or planning to take once registered to Step 1 a beta blocker, ARB, or ACE inhibitor in order to be randomized (Arms 1 and 2).
-Pts currently taking a beta blocker, ARB, or ACE inhibitor at the time of Step 1 Registration are eligible to register for the non-randomized observational cohort (Arm 3). Effective with the Status Notice distributed with Revision #5 (protocol Version Date 07/07/2021), Arm 3 is permanently closed to accrual
-Pts must not be currently taking or planning to take the following during study treatment or observation: B2 agonists, bosutinib, ceritinib, floctafenine, methacholine, pazopanib, rivastigmine, vincristine, silodosin.
-Pts must have a Zubrod of 0-2.
-Pts must be >/= 18 years of age.
-Pts must have a complete physical exam and medical Hx within 28 days prior to reg.
-Pts must have LVEF >/= 50% by 2-D Echo within 28 days prior to registration. The Echo must be obtained from a S1501 validated ECHO lab (see list of site �Validated ECHO Labs� on the S1501 protocol abstract page at www.swog.org) and submitted for central review by the S1501 ECHO Core Lab (see Section 15.2). ECHO should not be submitted for central read until pt has been otherwise deemed eligible.
-Pts must have adequate hepatic function as evidenced by all of the following w/i 28 days prior to reg: serum bilirubin < 3.0 x IULN), SGOT/AST and SGPT/ALT < 5.0 x IULN.
-Pts must have EKG with QTc with correction within 28 days prior to reg.
-Pts must have a systolic blood pressure >/= 80 mm Hg w/i 14 days prior to reg.
-Pts must not be dialysis dependent.
-Pts must be able to swallow tablets.
-Pts must not have uncontrolled asthma.
-Pts must not co-enroll on other treatment trials.
-No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer on active surveillance, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.
-Pts must not be pregnant or nursing due to potential fetal or nursing infant harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
-Pts must be willing to submit blood specimens as outlined in Section 15.1.
-Sites must seek additional pt consent for the future use of specimens as described in Section 15.0.

Step 2 Registration:

-Pts must not be registered to Step 2 until receiving confirmation via RAVE EDC that the patients LVEF by echo was >/= 50% by central review. Pts must be registered w/i 21 calendar days of submission of the ECHO study.
-Site must verify that there is no known change in the Step 1 eligibility since initial registration.