Dexrazoxane for Preventing Heart Failure

(PHOENIX1 Trial)

Overseen By Edward TH Yeh, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Arkansas

Disqualifiers: Pregnancy, Cardiac disease, Renal disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if early administration of Dexrazoxane, a cardioprotective drug, can prevent heart problems caused by Doxorubicin, a common cancer treatment. Researchers will test various doses of Dexrazoxane to identify the most effective one. Women who are generally healthy and have no history of heart or kidney issues may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking therapy.

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

The trial information does not specify if you need to stop taking your current medications.

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

Research has shown that dexrazoxane is generally safe for people. It significantly lowers the risk of heart failure caused by doxorubicin, a common cancer treatment. Specifically, one study found that dexrazoxane reduced the risk of heart failure by 2.5 to 4.5 times compared to a placebo, indicating a much lower likelihood of heart problems for those taking dexrazoxane. Additionally, dexrazoxane is the only drug approved by the FDA specifically to protect the heart from doxorubicin damage.

These studies suggest that dexrazoxane is safe for use, particularly in preventing heart issues during cancer treatment. However, as this trial is in its early stages, researchers continue to gather more information on its safety and the appropriate dosage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dexrazoxane for preventing heart failure because it offers a unique protective mechanism against heart damage caused by certain chemotherapy drugs. Unlike standard treatments, which often focus on managing symptoms or slowing heart failure, dexrazoxane works by chelating iron, reducing oxidative stress, and preventing damage to heart cells. This could potentially offer a proactive approach to heart protection, especially for patients undergoing chemotherapy, reducing the risk of heart failure before it starts. The trial investigates various doses, from 100mg/m² to 500mg/m², to determine the most effective and safe option.

What evidence suggests that this trial's treatments could be effective for preventing heart failure?

Research has shown that dexrazoxane can reduce the risk of heart failure caused by doxorubicin, a chemotherapy drug. Studies have found that dexrazoxane significantly lowers this risk. For example, one study found that the risk of heart failure dropped by about 78%. Dexrazoxane is recommended for patients at high risk of heart problems when taking drugs like doxorubicin. It is considered a top choice for preventing heart failure in these cases. Overall, the evidence supports dexrazoxane as a strong option to protect the heart during cancer treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Hui-Ming Chang, MD,MPH

Principal Investigator

University of Arkansas

Are You a Good Fit for This Trial?

This trial is for healthy women aged 18-65 who are not pregnant, not breastfeeding, and have no current illnesses. It's not open to those with a history of kidney or heart disease, or who are currently ill.

Inclusion Criteria

Not pregnant

I do not have any current illnesses.

I am a woman.

Exclusion Criteria

I have a history of kidney disease.

I have a history of heart disease.

I am currently ill.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one dose of dexrazoxane at varying dosages to study its effect on Topoisomerase 2b degradation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for degradation of Topoisomerase 2b and 2a in blood samples

48 hours

Blood samples collected

What Are the Treatments Tested in This Trial?

Interventions

• Dexrazoxane

Trial Overview The study is testing if Dexrazoxane given early can prevent heart damage caused by Doxorubicin, a drug used in cancer treatment. The focus is on preventing heart failure in patients receiving Doxorubicin.

How Is the Trial Designed?

Group I: Dexrazoxane 500mg/m2 Experimental Treatment 1 Intervention

one dose of 500 mg/m2

Group II: Dexrazoxane 400mg/m2 Experimental Treatment 1 Intervention

one dose of 400mg/m2 dexrazoxane

Group III: Dexrazoxane 300mg/m2 Experimental Treatment 1 Intervention

one dose of 300mg/m2 dexrazoxane

Group IV: Dexrazoxane 200mg/m2 Experimental Treatment 1 Intervention

one dose of 200mg/m2 dexrazoxane

Group V: Dexrazoxane 100mg/m2 Experimental Treatment 1 Intervention

one dose of 100mg/m2 dexrazoxane

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 205 children with high-risk acute lymphoblastic leukemia (ALL), dexrazoxane did not increase the risk of developing secondary malignant neoplasms (SMNs) compared to those who received doxorubicin alone, with a median follow-up of 6.2 years.

The results support the continued use of dexrazoxane as a cardioprotectant during doxorubicin treatment in pediatric patients, as no SMNs were observed in the dexrazoxane group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. Barry, EV., Vrooman, LM., Dahlberg, SE., et al.[2022]

In a 6-month study involving 305 patients with heart failure, candesartan significantly reduced the progression of heart failure (7.4% in the candesartan group vs. 22.2% in the placebo group), demonstrating a 63.8% risk reduction.

Candesartan also led to a significant decrease in cardiovascular events (10.8% vs. 22.9% in the placebo group), indicating its efficacy in improving heart health in patients who were either untreated or intolerant to ACE inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of angiotensin II receptor antagonist on heart failure]. Matsumori, A.[2021]

Long-term randomized control trials indicate that digoxin may only benefit a minority of heart failure patients, with mixed results from three studies (one positive, two negative).

Angiotensin-converting enzyme inhibitors like captopril and enalapril show consistent and significant improvements in exercise capacity and functional status in heart failure patients, suggesting they should be considered for initial treatment alongside diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of heart failure. A methodological review of the literature. Guyatt, GH.[2018]

In a study of 5436 heart failure patients without diabetes, those treated with candesartan had a lower incidence of developing diabetes (6.0%) compared to those on placebo (7.4%), indicating that candesartan may help prevent diabetes in this population.

Candesartan also reduced the combined risk of death or diabetes, with 25.2% of patients in the candesartan group experiencing this outcome compared to 28.6% in the placebo group, suggesting its potential benefits beyond heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure. Yusuf, S., Ostergren, JB., Gerstein, HC., et al.[2021]

Istaroxime, administered as a 24-hour infusion, significantly improved heart function in patients with acute heart failure, as evidenced by a greater reduction in the E/e' ratio compared to placebo, indicating better diastolic function.

The treatment also increased stroke volume and systolic blood pressure without causing major cardiac adverse effects, such as arrhythmias or hypotension, suggesting it is a safe option for improving heart function in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. Carubelli, V., Zhang, Y., Metra, M., et al.[2021]

In a study of 70 breast cancer patients undergoing anthracycline-based chemotherapy, the addition of dexrazoxane did not show a protective effect on ECG parameters associated with arrhythmia, as significant increases were observed in both groups after treatment.

Despite dexrazoxane's known role in preventing heart failure, the study found that ejection fraction decreased in both the dexrazoxane and non-dexrazoxane groups, indicating that it may not effectively protect against arrhythmia-related changes during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dexrazoxane effect on preventing acute cardiac arrhythmia in patients with breast cancer treated with neoadjuvant/adjuvant anthracycline-based chemotherapy. Kaplan, O., Bozdag Kaplan, N.[2022]

Doxorubicin, an anthracycline chemotherapy drug, can cause serious heart damage, leading to cardiomyopathy and heart failure, especially when the total dose exceeds 550 mg/m2.

Dexrazoxane has shown significant potential in preventing doxorubicin-induced heart damage by binding iron and reducing harmful free radicals, with promising results from both animal and human studies, although further research is needed to optimize its use alongside chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Seifert, CF., Nesser, ME., Thompson, DF.[2017]

Istaroxime is a promising new treatment for acute heart failure syndromes (AHFS) that works by improving heart contractility and diastolic relaxation without significantly affecting heart rate or blood pressure.

Early human studies show that istaroxime can decrease pulmonary capillary wedge pressure and improve diastolic function, with side effects primarily related to gastrointestinal issues, indicating a need for further research to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na-K-ATPase inhibition: a new promising treatment for acute heart failure syndromes? Khan, H., Metra, M., Blair, JE., et al.[2021]

In a small study of five patients with preexisting cardiomyopathy, the use of dexrazoxane allowed them to complete anthracycline chemotherapy without significant heart function decline, as their left ventricular ejection fraction (LVEF) only decreased slightly from 39% to 34%.

In contrast, three patients who did not receive dexrazoxane experienced severe heart function deterioration, with LVEF dropping from 42.5% to 18%, leading to symptomatic heart failure and two fatalities, highlighting dexrazoxane's potential as a protective agent in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series. Ganatra, S., Nohria, A., Shah, S., et al.[2022]

In a study involving Sprague-Dawley rats, dexrazoxane (DZR) significantly reduced infarct size and improved cardiac function after myocardial infarction, indicating its cardioprotective effects.

DZR treatment was associated with increased capillary density and bone marrow-derived endothelial progenitor cells, suggesting that its mechanism of action may involve promoting neovascularization and reducing apoptosis in heart tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis. Zhou, L., Sung, RY., Li, K., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11103024/

Dexrazoxane to Prevent Cardiotoxicity in Adults Treated ... In this population, dexrazoxane reduced the risk of HF (risk ratio: 0.22; 95% CI: 0.11-0.43) with no significant difference in oncologic ...

2. jacc.org jacc.org/doi/10.1016/j.jaccao.2024.01.004

Preventing Anthracycline-Associated Heart Failure: ... Dexrazoxane is listed as a Class 2a recommendation (Level of Evidence: B) for the primary prevention of AIC in adult patients at high and very high risk.

3. sciencedirect.com sciencedirect.com/science/article/pii/S095980492200168X

Long-term effectiveness of empiric cardio-protection in ... Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most ...

4. cardiooncologyjournal.biomedcentral.com cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-025-00323-8

Dexrazoxane makes doxorubicin-induced heart failure a rare ... This review examines the role of dexrazoxane in recent oncology trials involving sarcoma patients treated with high cumulative doses of doxorubicin.

5. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014638.pub2/full

Dexrazoxane for preventing or reducing cardiotoxicity in ... In adults, moderate‐quality evidence showed that there was less clinical heart failure with the use of dexrazoxane (risk ratio (RR) 0.22, 95% ...

6. mdpi.com mdpi.com/1424-8247/17/12/1739

Safety Evaluation of the Combination with Dexrazoxane ... The Cochrane analysis by de Baat EC et al. [36] confirmed that dexrazoxane can reduce the risk of cardiac failure (2.5–4.5-fold compared with the placebo) ...

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.008209

Clinically Translatable Prevention of Anthracycline ... Dexrazoxane (DEX)—the only drug approved for its prevention—has been believed to protect the heart via its iron-chelating metabolite ADR-925. However, direct ...