Vericiguat for Breast Cancer-Related Heart Failure

Overseen By Jennifer Liu, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Nitrates, Phosphodiesterase inhibitors

Disqualifiers: Hypertrophic cardiomyopathy, Uncontrolled arrhythmia, Severe hepatic insufficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use long-acting nitrates, NO donors, or phosphodiesterase inhibitors while participating.

How does the drug Vericiguat differ from other treatments for breast cancer-related heart failure?

Vericiguat is unique because it works by stimulating an enzyme called soluble guanylate cyclase, which helps relax blood vessels and improve blood flow, potentially offering a novel approach for heart failure related to breast cancer treatment, unlike traditional heart failure drugs that may not address this specific mechanism. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Anthony Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with biopsy-proven breast cancer and heart issues due to past cancer treatments. They must have a specific decrease in heart function, be able to do an exercise test, and use effective birth control if needed. People can't join if they have severe kidney, liver, lung diseases or other conditions that could interfere with the study.

Inclusion Criteria

My breast cancer diagnosis was confirmed through a biopsy.

I agree to use effective birth control during and for 30 days after the study.

My heart function has worsened due to cancer treatment.

Exclusion Criteria

I am currently using or plan to use a phosphodiesterase inhibitor.

I do not have any major heart, lung, or mental health issues that prevent me from exercising.

I do not have severe kidney, liver, or lung problems, or any other condition that would stop me from completing the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vericiguat or optimal medical therapy for cancer therapy-related cardiac dysfunction

6 months

Regular titration visits for dose adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vericiguat

Trial Overview The trial tests whether adding Vericiguat to standard heart failure treatment helps improve heart function in breast cancer patients who've developed cardiac dysfunction from previous cancer therapy better than standard treatment alone.

Participant Groups

Group I: Vericiguat plus optimal medical therapy Experimental Treatment 1 Intervention

For patients randomized to vericiguat, a starting dose of 2.5mg will be initiated at the randomization visit. At pre-specified titration visits, subjects will be up-titrated to vericiguat 5mg and then to the target dose of vericiguat 10mg using titration criteria based on mean systolic blood pressure and evaluation for clinical symptoms. Vericiguat will be administered in the background of optimal medical therapy for cardiomyopathy/heart failure.

Group II: Optimal medical therapy Active Control 1 Intervention

For patients randomized to the control group, optimal medical therapy for cardiomyopathy/heart failure will be instituted throughout the study period.

Vericiguat is already approved in United States, European Union for the following indications:

Approved in United States as Verquvo for:

• Heart failure

Approved in European Union as Verquvo for:

• Chronic heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Cancer patients are at risk of developing heart failure due to the combined effects of anticancer treatments, existing cardiovascular conditions, and the cancer itself, which can complicate treatment and worsen prognosis.

Recent guidelines from American and European cardiology organizations emphasize the importance of a multidisciplinary approach (cardio-oncology) to manage heart failure in cancer patients before and during cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of American and European guidelines for cardio-oncology of heart failure. Chen, JZ., Liang, B.[2023]

In a study of 628 women with breast cancer undergoing anthracycline chemotherapy, those receiving continuous statin therapy had a significantly lower risk of developing new-onset heart failure (HF), with a hazard ratio of 0.3, indicating a protective effect of statins.

The study suggests that statins may help prevent cardiotoxicity associated with chemotherapy, aligning with previous animal studies, and highlights the need for further research through prospective clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. Seicean, S., Seicean, A., Plana, JC., et al.[2012]

Breast and childhood cancer survivors are at increased risk of end-stage heart failure due to cardiotoxic treatments like anthracyclines and trastuzumab, with predictors of irreversible heart failure including age, renal dysfunction, and HER2 positivity.

Left ventricular assist devices (LVAD) and cardiac transplantation are viable options for treating chemotherapy-induced heart failure, with good long-term survival rates, although careful patient selection is crucial due to complications like right ventricular dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Advanced Heart Failure due to Cancer Therapy: the Present Role of Mechanical Circulatory Support and Cardiac Transplantation. Deo, SV., Al-Kindi, SG., Oliveira, GH.[2020]

Echocardiographic surveillance in breast cancer patients treated with anti-HER2 antibodies significantly reduced the incidence of cardiac dysfunction and acute heart failure, with only 2.1% of patients in the surveillance group reaching the composite endpoint compared to 5.5% in the non-surveillance group.

Patients undergoing echocardiographic monitoring were more likely to receive cardioprotective medications, suggesting that regular heart monitoring can lead to timely interventions that improve cardiac safety during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of surveillance by echocardiography for cancer therapeutics-related cardiac dysfunction of patients with breast cancer. Okushi, Y., Saijo, Y., Yamada, H., et al.[2023]

Cardiovascular events are a major concern for cancer survivors, as they can lead to significant health issues and impact cancer treatment options, particularly due to cancer therapeutics-related cardiac dysfunction (CTRCD).

Recent guidelines for managing CTRCD are primarily based on data from heart failure patients without cancer, highlighting a need for more specific research on cardioprotective strategies for newer cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chemotherapy-associated cardiomyopathy. Cai, AW., Taylor, MH., Ramu, B.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparison of American and European guidelines for cardio-oncology of heart failure. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. [2012]

3. United States pubmed.ncbi.nlm.nih.gov

Management of Advanced Heart Failure due to Cancer Therapy: the Present Role of Mechanical Circulatory Support and Cardiac Transplantation. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness of surveillance by echocardiography for cancer therapeutics-related cardiac dysfunction of patients with breast cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of chemotherapy-associated cardiomyopathy. [2020]