Carvedilol for Preventing Heart Failure in Childhood Cancer Survivors

No longer recruiting at 98 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: Beta blockers, CYP2D6 inhibitors

Disqualifiers: Cardiomyopathy, Hypertension, Asthma, Diabetes, others

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: 6

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low-dose carvedilol, a medication for heart conditions, can prevent heart failure in childhood cancer survivors who received high doses of anthracycline chemotherapy. Anthracyclines can harm the heart, raising the risk of heart failure, which occurs when the heart cannot pump blood effectively. Participants will be randomly assigned to take either carvedilol or a placebo (a pill with no active drug) for 24 months. The trial seeks individuals diagnosed with cancer before age 22, who completed treatment at least two years ago, and received high doses of anthracyclines without protective medication. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot use beta blockers or certain blood pressure medications within 30 days of enrollment. It's best to discuss your current medications with the trial team to see if any changes are needed.

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

Research has shown that carvedilol is generally safe for individuals who survived cancer as children. Studies have found it to be well-tolerated, even with long-term use. For example, research involving childhood cancer survivors who took carvedilol found it safe, although it did not significantly improve heart muscle thickness. Another study suggested that carvedilol might help lower the risk of heart failure in these patients without causing major side effects.

Overall, carvedilol is considered safe and may help reduce the risk of heart problems in childhood cancer survivors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Carvedilol is unique because it targets the prevention of heart failure in childhood cancer survivors, a group that often faces heart issues due to previous cancer treatments. Unlike standard heart failure medications, which are typically used to treat symptoms after they appear, carvedilol is being explored for its preventive potential. Researchers are excited about this treatment because it could offer a proactive approach, potentially safeguarding heart health before problems develop. This could be a game-changer for improving the long-term quality of life for childhood cancer survivors.

What evidence suggests that carvedilol might be an effective treatment for preventing heart failure in childhood cancer survivors?

Research has shown that carvedilol, which participants in this trial may receive, might help prevent heart failure in children who survived cancer and received high doses of anthracyclines, a type of chemotherapy. Studies found that carvedilol improved an important marker related to heart health, suggesting it could protect the heart. Although carvedilol appeared safe for long-term use, it did not significantly improve some heart function measures. Overall, carvedilol is considered promising because it may reduce the risk of heart failure. ^{6 7 8 9 10}

Who Is on the Research Team?

Saro H Armenian

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for childhood cancer survivors who are now at risk of heart failure due to high-dose anthracycline chemotherapy. Participants must weigh at least 40 Kg, have been diagnosed with cancer before age 22, finished treatment at least 2 years ago, and received a certain amount of anthracycline without dexrazoxane protection.

Inclusion Criteria

I received a high dose of a specific chemotherapy drug for cancer treated before I was 22.

I was diagnosed with cancer before turning 22.

I weigh at least 40 kg.

Exclusion Criteria

Your blood doesn't have enough red cells.

I don't have stomach or liver problems affecting medication absorption.

My hormone-related condition is not controlled by medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-dose carvedilol or placebo orally once or twice daily for 24 months

24 months

Regular visits at baseline, 6 months, 12 months, 18 months, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carvedilol

Trial Overview The study tests if low-dose Carvedilol can prevent heart failure in those exposed to high doses of anthracyclines during childhood cancer treatment. It includes lab biomarker analysis, pharmacogenomic and pharmacological studies, placebo comparison, quality-of-life assessment, and questionnaires.

How Is the Trial Designed?

Group I: Arm I (carvedilol) Experimental Treatment 6 Interventions

Patients receive low-dose carvedilol PO QD or BID for 24 months.

Group II: Arm II (placebo) Placebo Group 6 Interventions

Patients receive placebo PO QD or BID for 24 months.

Carvedilol is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Coreg for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in European Union as Dilatrend for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in Canada as Eucardic for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in Japan as Carloc for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.10013

Carvedilol for prevention of heart failure in anthracycline- ... We hypothesized that low-dose carvedilol would be safe and efficacious in reducing anthracycline-related heart failure risk in long-term ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10872217/

Effect of carvedilol versus placebo on cardiac function in ... Low-dose carvedilol appeared to be safe in long-term childhood cancer survivors at risk for HF, but did not result in significant improvement of LVWT/Dz ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02717507

Carvedilol in Preventing Heart Failure in Childhood Cancer ... This phase IIb trial studies how well low-dose carvedilol works in preventing heart failure in cancer survivors exposed to high dose anthracyclines for ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20303248

Carvedilol in Preventing Heart Failure in Childhood Cancer ... This randomized phase IIb trial studies how well low-dose carvedilol works in preventing heart failure in cancer survivors exposed to high dose anthracyclines.

5. ajmc.com ajmc.com/view/treatment-of-childhood-cancer-survivors-with-carvedilol-improved-biomarker-linked-to-heart-health-study-finds

Treatment of Childhood Cancer Survivors With Carvedilol ... Giving childhood cancer survivors the beta blocker carvedilol improved a key biomarker linked to heart damage, suggesting this low-cost ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11522501/

Carvedilol to Improve Cardiac Remodeling in Anthracycline ... A recent study of nearly 1,500 long-term childhood cancer survivors with normal baseline LVEF (≥50%) suggested that NT-proBNP and ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/07/NCT02717507/Prot_SAP_000.pdf

ALTE1621 Version Date: 12/08/2020 Page 1 CHILDREN'S ... We hypothesize that carvedilol delivered at a dose of 12.5 mg per day for two years will be an efficacious and safe option for HF risk reduction ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000001308

Cardiovascular Toxicity in Patients Treated for Childhood ... This document, focused on current data in pediatric patients and survivors of pediatric cancer, builds on the prior American Heart Association scientific ...

9. ascopost.com ascopost.com/news/january-2024/use-of-carvedilol-to-help-prevent-heart-failure-in-childhood-cancer-survivors/

Use of Carvedilol to Help Prevent Heart Failure in ... Researchers discovered that the blood vessel–relaxing agent carvedilol may be safe and effective at reducing the risk of heart failure in childhood cancer ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38215764/

Effect of carvedilol versus placebo on cardiac function in ... Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT ...