Carvedilol for Preventing Heart Problems in HER2 Positive Breast Cancer

Recruiting at 305 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Southwest Oncology Group

Must not be taking: B2 agonists, Bosutinib

Disqualifiers: Uncontrolled asthma, Dialysis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 12

Duration: 108 weeks

491 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether carvedilol, a medication typically used for heart failure and high blood pressure, can prevent heart problems in patients with HER2-positive breast cancer that has spread. Participants must be receiving trastuzumab-based therapy, a common treatment for this cancer type. The largest group is observational, focusing on patients already at risk for heart issues due to their cancer treatment. The trial seeks patients with metastatic breast cancer who are on trastuzumab-based therapy and have risk factors for heart problems, such as previous exposure to certain cancer treatments or a history of heart disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

If you are currently taking a beta blocker, ARB, or ACE inhibitor, you cannot participate in the randomized part of the trial but may join the non-randomized observational group. Additionally, you must not take certain medications like B2 agonists, bosutinib, and others during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that carvedilol is generally safe and well-tolerated in people with breast cancer. One study found it could be used without serious safety concerns during treatment. While scientists continue to study how well carvedilol protects the heart from cancer treatment side effects, it is already used to treat heart failure and high blood pressure. This extensive use provides doctors with substantial knowledge about its safety. Overall, carvedilol is considered a safe option for patients in clinical trials like this one. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about carvedilol for preventing heart problems in patients with HER2-positive breast cancer because it offers a potential cardioprotective benefit. Unlike typical heart medications for cancer patients, carvedilol is a beta-blocker that may help shield the heart from damage caused by cancer treatments. This is significant because it targets the heart's response to stress and inflammation, potentially reducing the risk of heart-related side effects without interfering with cancer therapies. By improving heart health during cancer treatment, carvedilol could enhance overall patient outcomes.

What evidence suggests that carvedilol might be an effective treatment for preventing heart problems in HER2-positive breast cancer patients?

In this trial, some participants will receive carvedilol. Studies have shown that carvedilol can protect the heart from damage caused by chemotherapy in cancer patients and lower the risk of heart problems during treatment. However, some research suggests that carvedilol may not effectively prevent heart issues in patients with HER2-positive breast cancer treated with trastuzumab. The evidence remains mixed, and while carvedilol is generally safe, its effectiveness in this specific situation is still under investigation. Other participants in this trial will either receive no intervention or be under observation to compare outcomes. ^{1 2 3 5 6}

Who Is on the Research Team?

Justin Floyd

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with HER-2-positive metastatic breast cancer who are starting or continuing trastuzumab-based therapy. They must have normal heart function, blood pressure, and not be on certain heart medications. Pregnant or nursing individuals can't join, nor those with other recent cancers except some specific cases.

Inclusion Criteria

Your heart's pumping ability must be at least 50% as measured by a special heart ultrasound within 28 days before joining the study.

Your liver enzyme levels are within five times the normal range.

Patients must not co-enroll on other treatment trials

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carvedilol or no intervention for up to 108 weeks, with courses repeating every 12 weeks for those on carvedilol

108 weeks

Regular visits every 12 weeks

Observation

Participants undergo observation for cardiac events and other outcomes

108 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

108 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carvedilol

Trial Overview The study tests if carvedilol can prevent heart damage in patients receiving cancer treatment for HER-2-positive metastatic breast cancer. It involves taking the beta-blocker carvedilol alongside standard chemotherapy to see if it reduces cardiac toxicity.

How Is the Trial Designed?

Group I: Arm I (carvedilol) Experimental Treatment 2 Interventions

Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive carvedilol PO BID. Courses repeat every 12 weeks for 108 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (no intervention) Active Control 1 Intervention

Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive no study intervention for up to 108 weeks.

Group III: Arm III (observation) Active Control 2 Interventions

Patients undergo observation for up to 108 weeks.

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a review of nine randomized controlled trials involving 717 patients, carvedilol showed potential benefits in preventing anthracycline-induced cardiotoxicity, particularly by improving left ventricular ejection fraction (LVEF) and possibly reducing the incidence of left ventricular systolic dysfunction (LVSD).

Despite these positive findings, the studies had significant variability in their definitions and reporting of LVSD, and there was no evidence of decreased mortality associated with carvedilol use, indicating the need for further research with larger sample sizes and longer follow-up periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive use of carvedilol for anthracycline-induced cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials. Zhan, T., Daniyal, M., Li, J., et al.[2022]

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 23 breast cancer patients undergoing anthracycline treatment, carvedilol showed a trend towards better right ventricular (RV) function compared to those receiving only chemotherapy, although the differences were not statistically significant.

The use of carvedilol was associated with a significantly higher RV S wave tissue Doppler imaging (S-TDI) measurement, suggesting a potential protective effect on RV function during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Effect of Carvedilol in Preventing Right Ventricular Dysfunction in Breast Cancer Patients Receiving Anthracycline. Karvandi, M., Ghadyani, M., Mohebbi, N., et al.[2023]

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]

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]

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 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]

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]

Citations

1. 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 ...

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

Risk-guided cardioprotection with carvedilol in patients ... This Phase 1 trial provides evidence that risk-guided cardioprotection with carvedilol at a dose of 6.25 mg twice daily is generally feasible, ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02177175

Carvedilol for the Prevention of Anthracycline/Anti-HER2 ... This phase II placebo-controlled study will evaluate the effect of carvedilol, compared to placebo, on anthracycline/anti-HER2 therapy induced left ventricular ...

4. withpower.com withpower.com/trial/phase-3-cardiotoxicity-8-2017-85ea2

Carvedilol for Preventing Heart Problems in HER2 Positive ... Carvedilol has been shown to lower the risk of heart damage caused by chemotherapy in cancer patients, as it reduces the incidence of noticeable heart problems ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.509

Lisinopril or carvedilol in prevention of trastuzumab- ... Background: Treatment of HER2-positive breast cancer patients with trastuzumab is highly effective. However, a trastuzumab-associated ...

6. stamfordhealth.org stamfordhealth.org/care-treatment/research/prospective-evaluation-of-carvedilol-in-prevention-of-cardiac-toxicity-in-patients-with-metastatic-her-2-breast-cancer--swog-s1

Clinical Trial Details Clinical Trial Details · Prospective Evaluation of Carvedilol in Prevention of Cardiac Toxicity in Patients with Metastatic HER-2+ Breast Cancer (SWOG S1501).