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Clinical Trial 19646

Cancer Type: Breast
Study Type: Treatment
NCT#: NCT03418961

Phase: Phase III
Principal Investigator: Extermann, Martine

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

Prospective Evaluation of Carvedilol in Prevention of Cardiac Toxicity in Patients with Metastatic HER-2+ Breast Cancer, Phase III

Summary

This phase III trial studies how well carvedilol works in preventing cardiac toxicity in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer that has spread to other places in the body. A beta-blocker, such as carvedilol, is used to treat heart failure and high blood pressure, and it may prevent the heart from side effects of chemotherapy.

Objective

Primary Objective: To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction in patients with metastatic breast cancer receiving trastuzumab based HER-2 targeted therapy. Secondary Objectives: a. To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of predefined subsequent cardiac events in patients with metastatic breast cancer receiving trastuzumab¿based HER-2 targeted therapy. b. To evaluate if prophylactic carvedilol compared with no intervention results in a longer time to first interruption of trastuzumab based HER-2 targeted therapy due to either cardiac dysfunction or events. with no intervention reduces the risk of subsequent cardiac dysfunction OR events in this population. d. To establish and prospectively collect a predefined panel of baseline core cardiovascular measures and develop a predictive model of cardiac dysfunction. e. To evaluate the rate of cardiac dysfunction in an observational arm consisting of individuals otherwise eligible for the study except for use of beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitors for other medical reasons. 1.3 Translational Objectives a. To evaluate the lle655Val and Alall70Pro single nucleotide polymorphisms (SNPs) of the HER-2 gene as a predictive biomarker of study-defined cardiac dysfunction. b. To evaluate plasma neuregulin-1 at baseline and over study time as a predictive biomarker of study-defined cardiac dysfunction. c. To evaluate the feasibility of performing serial left ventricular strain in an NCTN group setting, with the goal of 75% of patients contributing both a baseline and at least one follow-up strain measurement. d. To bank blood for future translational medicine studies such as brain natriuretic peptide (BNP), additional SNPs, and high sensitivity troponin.

Treatments

Therapies

Therapy (NOS)

Medications

Carvedilol (); Not Applicable ()

Inclusion Criteria

STEP 1 REGISTRATION

Participants must have metastatic breast cancer and be initiating within 7 days of step 1 registration or continuing trastuzumab based HER-2 targeted therapy without concurrent anthracyclines in first or second line setting; Participants may have brain metastasis; there is no limit for number of doses of HER-2 targeted therapy prior to registration

Participants must be at increased risk for cardiotoxicity defined by at least one of the following: (1) Previous anthracycline exposure, OR (2) 1 or more of the following risk factors for heart disease: Left ventricular ejection fraction (LVEF) 50-54% by local echocardiography (ECHO) read, over age 65, Body mass index (BMI) >= 30 kg/m^2, Current or prior anti-hypertensive therapy, Diagnosis of coronary artery disease (CAD), Diabetes mellitus, Atrial fibrillation/flutter.

Participants must have a Zubrod Performance status of 0-2

Participants must have a complete physical examination and medical history within 28 days prior to registration

Participants must have LVEF >= 50% by 2-dimensional (D) echocardiogram within 28 days prior to registration; the echocardiogram must be obtained from a S1501 validated ECHO laboratory (lab) and submitted for central review by the S1501 ECHO core lab; ECHO should not be submitted for central read until Participant has been otherwise deemed eligible. Participants must be planning on having ECHO’s completed and submitted every 12 weeks

Serum bilirubin > Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) > Participants must have electrocardiogram with corrected QT (QTc) with correction within 28 days prior to registration

Participants must have a systolic blood pressure >= 80 mm Hg within 14 days prior to registration

Participants must be able to swallow tablets

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 Participant is currently in complete remission, or any other cancer from which the Participant has been disease free for five years

Participants must be willing to submit blood specimens

Exclusion Criteria

STEP 1

Participants must not have taken within 21 days prior to step 1 registration, be currently taking at the time of step 1 registration, 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). Participants 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)

Participants must not be currently taking or planning to take during study treatment the following medications: B2 agonists, Bosutinib, Ceritinib, Floctafenine, Methacholine, Pazopanib, Rivastigmine, Vincristine, Silodosin

Participants must not be dialysis dependent

Participants must not have uncontrolled asthma

Participants must not co-enroll on other treatment trials

Participants 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, a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate Participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.

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