Carvedilol for Heart Protection in Breast Cancer Patients

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Beta-blockers, ACE inhibitors

Disqualifiers: LV dysfunction, Metastatic cancer, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to protect heart health in breast cancer patients undergoing certain chemotherapy treatments known to cause heart issues. It tests whether carvedilol, a medication, can prevent heart problems during chemotherapy. Participants receive either carvedilol or are monitored without the drug to compare outcomes. The trial seeks women with early-stage breast cancer who have a specific tumor marker (HER2) and are set to receive particular chemotherapy drugs. It is ideal for those with healthy heart function and no severe heart disease symptoms. As a Phase 2 trial, it measures how well carvedilol works in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications, except if you are on beta-blockers or ACE inhibitors, which are not allowed. Other cardiac and non-cardiac medications are permitted.

Is there any evidence suggesting that Carvedilol is likely to be safe for humans?

Research shows that carvedilol is usually well tolerated. It has been safely used for heart issues such as heart failure and high blood pressure, suggesting it might also be safe for individuals with breast cancer. No major reports of serious side effects have emerged when used to protect the heart in these patients. However, like any medicine, it may cause some side effects, so monitoring individual responses is important. For concerns, discuss expectations with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for heart protection in breast cancer patients, which often includes close monitoring and cardioprotective medications like ACE inhibitors or beta-blockers, Carvedilol is unique because it may offer a dual benefit. Not only does it act as a beta-blocker to manage heart rate and blood pressure, but it also has antioxidant properties that might provide additional heart protection. Researchers are excited about Carvedilol because it targets heart health in a more comprehensive way, potentially minimizing the cardiac side effects of cancer treatments while still supporting overall cardiovascular function.

What evidence suggests that Carvedilol might be an effective treatment for heart protection in breast cancer patients?

Research has shown that carvedilol may protect the heart from damage caused by certain breast cancer treatments, such as anthracyclines and trastuzumab, which can sometimes lead to heart problems. In this trial, participants in the "Prophylactic Carvedilol" arm will receive carvedilol to assess its effectiveness in preventing heart issues. One study found that carvedilol helped prevent heart issues in patients taking these drugs. However, another study found that carvedilol did not always have a significant protective effect. Overall, carvedilol has shown potential in reducing the risk of heart-related side effects during cancer treatment, but results have varied. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for women over 18 with early-stage HER2-positive breast cancer (Stages I-III) who are about to start treatment with specific chemotherapies known to affect the heart. They must have normal heart function and agree to use contraception. Excluded are those with severe pre-existing heart conditions, certain other health issues like severe asthma or liver dysfunction, pregnant/breastfeeding women, and anyone previously on beta-blockers.

Inclusion Criteria

Patients must have a signed informed consent prior to registration

I have a history of high blood pressure, high cholesterol, diabetes, or mild heart issues.

Women of childbearing potential and sexually active men and women should use effective contraception

Exclusion Criteria

I have never taken BB/ACE therapy.

Patients who are pregnant/lactating are not eligible

Unwilling to consent/assent to blood donation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline echocardiogram and blood draw for biomarkers and genetic testing

1 visit

1 visit (in-person)

Treatment

Participants receive chemotherapy with anthracycline and/or trastuzumab and pertuzumab, with echocardiograms every 3 months and potential prophylactic carvedilol treatment

12 months

Every 3 weeks during titration phase, then every 3 months

Biomarker Substudy

Biomarker labs drawn at baseline and every 6 weeks for 12 months, and 1 year post-chemotherapy

12 months

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including echocardiograms and biomarker analysis

1 year post-chemotherapy

What Are the Treatments Tested in This Trial?

Interventions

• Carvedilol

Trial Overview The study tests whether Carvedilol, a beta-blocker medication, can prevent or delay heart damage in patients receiving chemotherapy that's tough on the heart. Patients' hearts will be monitored using advanced imaging techniques to detect early signs of strain or damage during their cancer treatment.

How Is the Trial Designed?

Group I: Prophylactic Carvedilol Experimental Treatment 1 Intervention

Carvedilol 3.125 mg by mouth every 12 hours, titrated to a max dose of 25 mg by mouth every 12 hours, depending on blood pressure and heart rate, until completion of study.

Group II: No Therapy Active Control 1 Intervention

Standard of care monitoring without prophylactic treatment.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

Carvedilol significantly reduces cardiac damage caused by severe hypertension in stroke-prone spontaneously hypertensive rats, with reductions in various histopathologic indices such as coronary artery hypertrophy and myocardial inflammation by up to 100%.

Despite not affecting systolic blood pressure, carvedilol effectively prevents cardiac remodeling and myopathies associated with a high-salt, high-fat diet, demonstrating its potential for cardioprotection without lowering systemic blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol prevents severe hypertensive cardiomyopathy and remodeling. Barone, FC., Campbell, WG., Nelson, AH., et al.[2019]

In a study of 40 breast cancer patients undergoing chemotherapy, the combination of low-dose carvedilol and candesartan significantly reduced the acute and chronic cardiotoxic effects of anthracycline drugs compared to chemotherapy alone.

Patients receiving the combination treatment maintained better left ventricular ejection fraction (LVEF) and had lower rates of cardiac abnormalities, indicating that this approach may effectively protect heart health during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer]. Liu, L., Liu, ZZ., Liu, YY., et al.[2021]

Carvedilol significantly improves left ventricular ejection fraction (LVEF) and reduces mortality in patients with chronic heart failure (CHF), as shown in multiple studies including the US Carvedilol Heart Failure Trials Program with 1094 participants.

Compared to metoprolol, carvedilol demonstrated lower mortality rates in patients with CHF, indicating it may be the preferred beta-blocker for treatment, while also being well tolerated with fewer adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol: a review of its use in chronic heart failure. Keating, GM., Jarvis, B.[2022]

New drugs, specifically cyclin-dependent kinase (CDK) 4/6 inhibitors like palbociclib, ribociclib, and abemaciclib, have shown significant success in treating advanced and metastatic hormone receptor-positive breast cancer, especially when combined with hormone therapies.

As these oral medications become widely used, it is crucial for healthcare providers to ensure that patients understand their treatment regimens and support them in making informed decisions about their therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Oral Oncolytic Agents for Breast Cancer and Recommendations for Promoting Adherence. Gillespie, TW.[2021]

Carvedilol (CAR) significantly reduces the migration and invasion of breast cancer cells, indicating its potential as an anti-metastatic agent.

The mechanism of action involves the inhibition of Src activation through different signaling pathways: the cAMP/PKA-Src pathway in MDA-MB-231 cells and the PKCδ-Src pathway in MCF-7 cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol suppresses migration and invasion of malignant breast cells by inactivating Src involving cAMP/PKA and PKCδ signaling pathway. Dezong, G., Zhongbing, M., Qinye, F., et al.[2019]

A study assessed the pharmaceutical quality of Dilatrend (carvedilol) and 35 generic products, revealing that while all Dilatrend strengths met specifications, nearly 49% of the generics failed to meet key quality standards.

The failure of many generic products in tests for carvedilol content, tablet hardness, dissolution, and purity raises concerns about their efficacy and safety, suggesting that substituting Dilatrend with these generics could lead to unpredictable treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are generic formulations of carvedilol of inferior pharmaceutical quality compared with the branded formulation? Smith, JC., Tarocco, G., Merazzi, F., et al.[2018]

In a systematic review of six randomized controlled trials involving beta-blocker carvedilol, there was no significant difference in left ventricular ejection fraction (LVEF) after chemotherapy compared to placebo, indicating it may not prevent early asymptomatic heart function decline.

However, carvedilol was associated with a lower incidence of clinically overt cardiotoxicity and prevented increases in left ventricular end-diastolic diameter, suggesting it may help protect against more severe heart damage during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective role of beta-blockers in chemotherapy-induced cardiotoxicity-a systematic review and meta-analysis of carvedilol. Huang, S., Zhao, Q., Yang, ZG., et al.[2020]

The combination of palbociclib, pembrolizumab, and letrozole was found to be well tolerated in women with hormone receptor positive (HR+) HER2- metastatic breast cancer, with a complete response rate of 31% in the second cohort of the trial.

Patients experienced significant progression-free survival of 25.2 months and overall survival of 36.9 months, indicating promising efficacy of this treatment regimen as a front-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Yuan, Y., Lee, JS., Yost, SE., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006281/

Risk-guided cardioprotection with carvedilol in patients ... In this Phase 1 randomized clinical trial, risk-guided carvedilol appeared to be generally feasible, safe, and tolerable during breast cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8888356/

Evaluation of the Preventive Effects of Carvedilol on ... Conclusion: According to our results, in patients with HER2-positive breast cancer treated with trastuzumab, Carvedilol showed no significant protective effect ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804921000496

Carvedilol blocks neural regulation of breast cancer ... Original Research. Carvedilol blocks neural regulation of breast cancer progression in vivo and is associated with reduced breast cancer mortality in patients.

4. withpower.com withpower.com/trial/phase-3-cardiovascular-abnormalities-3-2015-becdf

Carvedilol for Heart Protection in Breast Cancer Patients Carvedilol has been shown to help prevent heart damage caused by chemotherapy in cancer patients, reducing the risk of heart-related side effects. It also ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109719347916

Randomized Trial of Lisinopril Versus Carvedilol to Prevent ... In patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.054698

Prevention of Cardiac Dysfunction During Adjuvant Breast ... This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial ...