A Study of Vericiguat in People With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction

Breast Cancer Clinical Trial

Official title:

A Randomized Controlled Trial of the Soluble Guanylate Cyclase Stimulator Vericiguat in Patients With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction (ELEVATE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05806138
• Other study ID #: 23-050
• Status: Recruiting
• Phase: Phase 2
• Start date: July 17, 2023
• Est. completion date: July 17, 2028

Study information

• Verified date: November 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Anthony Yu, MD
• Phone: 212-639-7932
• Email: yua3[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out if adding vericiguat to standard treatment for cancer therapy related cardiac dysfunction (CTRCD) is more effective than standard treatment alone. The addition of vericiguat to the usual treatment could help improve cardiac function, but it could also cause side effects. This study will help researchers find out whether this different treatment is better, the same as, or worse than the usual approach.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 17, 2028
• Est. primary completion date: July 17, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Biopsy proven breast cancer (stage I-IV)

• Cancer treatment related cardiac dysfunction (CTRCD), established by an absolute decrease in LVEF = 10% from baseline/pre-treatment to < 53% and attributable to prior cardiotoxic cancer treatment, per the clinical investigator.

• Able to complete an acceptable baseline CPET, in the absence of high-risk ECG findings or other inappropriate response to exercise as determined by the PI, as defined by any of the following criteria:

• Achieving a plateau oxygen consumption, concurrent with an increase in power output;

• A respiratory exchange ratio = 1.00;

• Attainment of maximal predicted heart rate, as defined by a peak heart rate within 10bpm of the age predicted maximal heart rate (220 - Age[years]); or if on a beta-blocker, 164 - (age * 0.7)

• Volitional exhaustion, as measured by a rating of perceived exertion (RPE) = 18 on the BORG scale.

• Willing to use highly effective contraceptive measures if of child-bearing potential or if the patient's sexual partner is a woman of child-earing potential while receiving study drug and for 30 days after the last dose of study drug:

• Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments

• Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the postmenopausal range for the institution

• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation.

• Male subjects should be willing to use barrier contraception °Willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

• Systolic blood pressure < 90 mmHg

• Concurrent or anticipated use of a long-acting nitrate or NO donor (e.g., nitroglycerin, isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal NTG patch, or molsidomine).

• Concurrent or anticipated use of a phosphodiesterase inhibitor (e.g., vardenafil, tadalafil, or sildenafil).

• Cardiac comorbidity, including any of the following:

• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac sarcoidosis, or amyloid cardiomyopathy

• Uncontrolled arrhythmia

• Uncorrected congenital cardiac disease

• Acute coronary syndrome, percutaneous coronary intervention, or coronary artery bypass graft surgery within 3 months prior to randomization.

• Symptomatic carotid stenosis, or transient ischemic attack (TIA) or stroke within 3 months prior to randomization.

• Cardiac transplantation

• Valvular heart disease requiring surgery or intervention

• Non-cardiac comorbidity, including any of the following:

• eGFR < 15ml/min/1.73m^2 (based upon CKD-EPI, Cockroft-Gault, etc.)

• Severe hepatic insufficiency (e.g., Child-Pugh C)

• Severe pulmonary disease, such as requiring continuous home oxygen or interstitial lung disease

• Other medical disorder or condition that in the opinion of the investigator would impair the subject's ability to participate or complete the study

• Subjects must not have any of the following absolute contraindications to cardiopulmonary exercise testing:

• Acute myocardial infarction (within 30 days of any planned study procedures)

• Unstable angina

• Uncontrolled arrhythmias causing symptoms or hemodynamic compromise,

• Symptomatic severe aortic stenosis

• Recurrent syncope

• Active endocarditis

• Acute myocarditis or pericarditis

• Acute pulmonary embolus or pulmonary infarction (within 3 months of any planned study procedures)

• Thrombosis of lower extremities (within 3 months of any planned study procedures)

• Suspected dissecting aneurysm

• Uncontrolled asthma

• Pulmonary edema

• Room air desaturation at rest =85%

• Respiratory failure

• Acute noncardiopulmonary disorder that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)

• Mental impairment leading to inability to cooperate.

• Current alcohol and/or drug abuse

• Any other condition or intercurrent illness (e.g., symptomatic weight-bearing bone metastases or limited life expectancy < 6-9 months) that, in the opinion of the investigator, makes the participant a poor candidate for the trial

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cardiac Dysfunction

Intervention

Drug:
• Vericiguat
A starting dose of vericiguat 2.5 mg will be administered in-clinic at the Day 1 visit. Titration visits will occur on Days 14 and 28, with dose escalation to 5 mg and 10 mg.

Other:
• Optimal medical therapy
All subjects will be followed by a cardiologist throughout the study period and will receive optimal medical therapy for cardiomyopathy/heart failure following the ACCF/AHA and ESC Guidelines for the Management of Heart Failure recommendations, applied individually at the discretion of the treating investigator and in line with individual tolerability. This includes medications such as ßblockers, angiotensin converting enzyme inhibitors(ACEI), angiotensin receptor/neprilysin inhibitor (ARNI), angiotensin receptor blockers (ARB), and mineralocorticoid antagonists

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in CRF (measured by VO2peak)	For the primary analysis, intervention effect will be evaluated by comparing differences in mean VO2peak changes from baseline to month 6 between the investigational and control groups using the analysis of covariance approach (ANCOVA).	up to 6 months
Secondary	CRF response rate	assessed by the number of participants with a change in VO2peak = 1.32 ml O2 • kg-1 • min-1 (technical error of CRF measurement) from baseline to month 6. A change in VO2peak = 1.32 ml O2 • kg-1 • min-1 will be considered a response, whereas a change in VO2peak < 1.32 ml O2 • kg-1 • min-1 will be considered a non-response.	up to 6 months

External Links

•   Memorial Sloan Kettering Cancer Center