Carvedilol for Cardioprotection in Breast Cancer

(CCTGuide Pilot Trial)

Overseen By Bonnie Ky, MD, MSCE

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Antidepressants, Digoxin, Beta blockers

Disqualifiers: Pregnancy, Asthma, Hepatic impairment, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 27

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether carvedilol, a heart medication, can protect the hearts of breast cancer patients receiving doxorubicin or trastuzumab, which are known to affect heart health. Researchers aim to determine if using carvedilol alongside usual cancer treatments is safe and manageable. Women diagnosed with Stage I-III breast cancer and scheduled for treatment with these chemotherapy drugs may be eligible. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications for the trial?

Yes, you will need to stop taking certain medications like Bupropion, Fluoxetine, Paroxetine, Quinidine, Duloxetine, Digoxin, and any beta blockers to participate in this trial.

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

Research has shown that carvedilol is usually well-tolerated by patients. Often used for heart problems, it is known to help protect the heart. In studies with breast cancer patients, researchers tested carvedilol to see if it could protect the heart during cancer treatment. Although it did not always show a strong protective effect against heart issues, it did not cause major side effects either. Most people handle carvedilol well, with tiredness or dizziness being the most common side effects.

Since this trial is in an early phase, the main focus is to ensure carvedilol's safety for breast cancer patients. Researchers are carefully observing participants' reactions to the drug. While carvedilol has been safe in other uses, they aim to confirm its safety specifically for breast cancer patients undergoing treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer-related heart issues, which often focus on managing symptoms, carvedilol offers a proactive approach by potentially protecting the heart from chemotherapy-induced damage. Carvedilol is a beta-blocker that works uniquely by blocking certain receptors in the heart, reducing heart rate and blood pressure, which could help prevent cardiac stress during cancer treatment. Researchers are excited about carvedilol because it targets cardioprotection directly, offering hope for reducing heart problems in breast cancer patients who undergo chemotherapy.

What evidence suggests that carvedilol might be an effective treatment for cardioprotection in breast cancer patients?

Research has shown that carvedilol might help protect the heart in breast cancer patients undergoing certain treatments. In this trial, some participants will receive carvedilol, which studies have found can lower troponin levels, a marker of heart damage, during cancer treatment. Another study associated carvedilol with less heart strain in patients with HER2+ breast cancer. Although one study did not achieve its main goal of preventing a significant drop in heart function, carvedilol still demonstrated potential benefits for heart health. These findings suggest that carvedilol might help protect the heart during breast cancer therapy. ^{1 6 7 8 9}

Who Is on the Research Team?

Bonnie Ky, MD, MSCE

Principal Investigator

Perelman School of Medicine at the University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for women over 18 with Stage I-III breast cancer who are about to receive anthracyclines and/or trastuzumab. They must have a measurable heart function score and not be pregnant or breastfeeding. Exclusions include asthma, current beta blocker use, low blood pressure, certain heart conditions, severe liver issues, and use of specific medications.

Inclusion Criteria

I am female.

My study team can get all needed heart health info, including an echo.

I have Stage I-III breast cancer and will be treated with anthracyclines or trastuzumab.

Exclusion Criteria

Your resting heart rate is below 55 beats per minute, which could indicate a serious heart condition.

You are allergic to carvedilol.

You have a history of asthma or similar breathing issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carvedilol in a risk-guided strategy alongside doxorubicin and/or trastuzumab

12 months

Visits at baseline and approximately 3, 6, 9, 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at approximately 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Carvedilol

Trial Overview The study tests if Carvedilol can protect the hearts of breast cancer patients from damage caused by chemotherapy drugs like doxorubicin and trastuzumab. It's compared to usual care without Carvedilol to see if it's safe and tolerable.

How Is the Trial Designed?

Group I: Carvedilol Experimental Treatment 1 Intervention

Carvedilol will be initiated at 3.125mg twice daily and uptitrated as tolerated in a stepwise fashion to a maximum dose of 25mg twice daily or to a systolic blood pressure (SBP) of 110-120mmHg or heart rate (HR) of 50-55 beats per minute (bpm). Patients will start carvedilol in the evening after first dose of chemotherapy and will continue on medication for 12 months. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months.

Group II: Usual Care Active Control 1 Intervention

Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and standardized time intervals during and after therapy at approximately 3, 6, 9, 12, and 24 months.

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39605014

A strain-guided trial of cardioprotection in early-stage ... This randomized clinical trial assessed if treatment with carvedilol based on a strain-guided strategy can prevent development of CTRCD in HER2+ breast cancer ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04023110

Risk-Guided Cardioprotection with Carvedilol in Breast ... This is a single-center, randomized clinical trial that seeks to determine if a risk guided treatment strategy that initiates carvedilol in high risk breast ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0002870325000456

Effects of carvedilol on the prevention of cardiotoxicity ... The study did not meet its primary efficacy outcome of reduction of LVEF ≥10% at 6 months, although carvedilol was associated with lower troponin rise and less ...

5. cardiooncologyjournal.biomedcentral.com cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-024-00291-5

A strain-guided trial of cardioprotection in early-stage breast ... This randomized clinical trial assessed if treatment with carvedilol based on a strain-guided strategy can prevent development of CTRCD in HER2+ breast cancer ...

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

Carvedilol blocks neural regulation of breast cancer ... Results. Treatment with carvedilol blocked the effects of sympathetic nervous system activation, reducing primary tumour growth and metastasis in a mouse model ...

7. 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 ...

8. 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 ...

9. trial.medpath.com trial.medpath.com/clinical-trial/045abd8895c64f4b/nct04023110-pilot-study-carvedilol-breast-cancer-patients

Risk-Guided Cardioprotection with Carvedilol in Breast ... Investigators will evaluate the safety, tolerability, and feasibility of a risk-guided cardioprotective treatment strategy with carvedilol, ...