Degradation of Top2b and Top2a in Human by DexrazoxanePhase 1PHOENIX1NCT03930680

Prevention of Heart Failure Induced by Doxorubicin With Early Administration of Dexrazoxane

A Phase 1 study testing Dexrazoxane in people with Degradation of Top2b and Top2a in Human by Dexrazoxane and Time Course and Degradation of Top2b in Human by Dexrazoxane, run by University of Arkansas at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity. Read more about this study

Who is it for?: Ages 18 to 65 years, women onlyHealthy volunteers can take part
Conditions the study is for: Degradation of Top2b and Top2a in Human by Dexrazoxane, Time Course and Degradation of Top2b in Human by Dexrazoxane, Effects of Dexrazoxane on Healthy Human
What is being tested?: Dexrazoxane
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteUnited States
Study dates: 14 Sep 2021to 11 Jun 2025
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Women,
Age 18-65,
Not pregnant, Not currently breast feeding
No current illness,

Who cannot join

Pregnancy, currently breast feeding
Current illness,
History of cardiac, or renal disease

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205

Other trials in United States

About this study

Official title: Prevention of Heart Failure Induced by Doxorubicin With Early Administration of Dexrazoxane in Patients With Breast Cancer

The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity.

Read the detailed description

This is a study on volunteers to determine effective dose of dexrazoxane in degrading Topoisomerase 2 b in human blood samples. Each participant will receive one dose of dexrazoxane. Blood samples will be collected to determine the time course and degradation of Topoisomerase 2b and Topoisomerase 2a

Conditions: Degradation of Top2b and Top2a in Human by Dexrazoxane, Time Course and Degradation of Top2b in Human by Dexrazoxane, Effects of Dexrazoxane on Healthy Human
Being tested: Dexrazoxane
Keywords: Dexrazoxane, Topoisomerase 2b, Human, Doxorubicin cardio-toxicity, Cardio-oncology, Onco-cardiology, Prevention of cardio-toxicity by doxorubicin, Early administration of dexrazoxane

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DexrazoxaneDrug
Also called Zinecard
One dose of dexrazoxane

Study groups in NCT03930680
Study group	Role	What they receive
Dexrazoxane 100mg/m2	Experimental	one dose of 100mg/m2 dexrazoxane Receives: Drug: Dexrazoxane
Dexrazoxane 200mg/m2	Experimental	one dose of 200mg/m2 dexrazoxane Receives: Drug: Dexrazoxane
Dexrazoxane 300mg/m2	Experimental	one dose of 300mg/m2 dexrazoxane Receives: Drug: Dexrazoxane
Dexrazoxane 400mg/m2	Experimental	one dose of 400mg/m2 dexrazoxane Receives: Drug: Dexrazoxane
Dexrazoxane 500mg/m2	Experimental	one dose of 500 mg/m2 Receives: Drug: Dexrazoxane

What is being measured

The primary outcome is the main question the study is designed to answer.

Participants With 95% Reduction in Topoisomerase 2 b From Baseline
Number of participants with 95% reduction in topoisomerase 2 b from baseline is reported in the Outcome Measure Data Table
Measured: 8 hours after dexrazoxane administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Sep 202111 Jun 2025

First posted29 Apr 2019
Study start14 Sep 2021
Primary completion11 Jun 2024
Study completion11 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (27)Papers the sponsor has linked to this study.
Other trials for Degradation of Top2b and Top2a in Human by DexrazoxaneStudies of the same condition, open and under way.
More trials run by University of ArkansasThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: Each subject will receive one dose of dexrazoxane.
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03930680
Sponsor's protocol ID: 262180
Other IDs: R01HL151993
Acronym: PHOENIX1
Status last verified: Jun 2025
First submitted: 25 Apr 2019
Last updated: 8 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. J Am Coll Cardiol. 2017 Nov 14;70(20):2536-2551. doi: 10.1016/j.jacc.2017.09.1096.
PubMed 29145954
Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012 Nov;18(11):1639-42. doi: 10.1038/nm.2919. Epub 2012 Oct 28.
PubMed 23104132
Lipshultz SE, Lipsitz SR, Kutok JL, Miller TL, Colan SD, Neuberg DS, Stevenson KE, Fleming MD, Sallan SE, Franco VI, Henkel JM, Asselin BL, Athale UH, Clavell LA, Michon B, Laverdiere C, Larsen E, Kelly KM, Silverman LB. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013 Oct 1;119(19):3555-62. doi: 10.1002/cncr.28256. Epub 2013 Jul 16.
PubMed 23861158
Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984 Oct 26;226(4673):466-8. doi: 10.1126/science.6093249.
PubMed 6093249
Olson LE, Bedja D, Alvey SJ, Cardounel AJ, Gabrielson KL, Reeves RH. Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1. Cancer Res. 2003 Oct 15;63(20):6602-6.
PubMed 14583452
Azuma Y, Arnaoutov A, Dasso M. SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol. 2003 Nov 10;163(3):477-87. doi: 10.1083/jcb.200304088. Epub 2003 Nov 3.
PubMed 14597774
Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, Liu LF. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007 Sep 15;67(18):8839-46. doi: 10.1158/0008-5472.CAN-07-1649.
PubMed 17875725
Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, Jones SE, Wadler S, Desai A, Vogel C, Speyer J, Mittelman A, Reddy S, Pendergrass K, Velez-Garcia E, Ewer MS, Bianchine JR, Gams RA. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997 Apr;15(4):1318-32. doi: 10.1200/JCO.1997.15.4.1318.
PubMed 9193323
Bluethmann SM, Mariotto AB, Rowland JH. Anticipating the "Silver Tsunami": Prevalence Trajectories and Comorbidity Burden among Older Cancer Survivors in the United States. Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1029-36. doi: 10.1158/1055-9965.EPI-16-0133.
PubMed 27371756
Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 2. J Am Coll Cardiol. 2017 Nov 14;70(20):2552-2565. doi: 10.1016/j.jacc.2017.09.1095.
PubMed 29145955
Armstrong GT, Kawashima T, Leisenring W, Stratton K, Stovall M, Hudson MM, Sklar CA, Robison LL, Oeffinger KC. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol. 2014 Apr 20;32(12):1218-27. doi: 10.1200/JCO.2013.51.1055. Epub 2014 Mar 17.
PubMed 24638000
Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K, Mabuchi K, Marks LB, Mettler FA, Pierce LJ, Trott KR, Yeh ET, Shore RE. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):656-65. doi: 10.1016/j.ijrobp.2009.09.064.
PubMed 20159360
Swain SM, Vici P. The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review. J Cancer Res Clin Oncol. 2004 Jan;130(1):1-7. doi: 10.1007/s00432-003-0498-7. Epub 2003 Oct 17.
PubMed 14564513
Yeh ET, Chang HM. Oncocardiology-Past, Present, and Future: A Review. JAMA Cardiol. 2016 Dec 1;1(9):1066-1072. doi: 10.1001/jamacardio.2016.2132.
PubMed 27541948
Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. doi: 10.1002/1097-0142(1967)20:33.0.co;2-k. No abstract available.
PubMed 4290058

Study at a glance

From the registry record, last updated by the sponsor on 8 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prevention of Heart Failure Induced by Doxorubicin With Early Administration of Dexrazoxane in Patients With Breast Cancer
ClinicalTrials.gov ID: NCT03930680
Acronym / sponsor ID: PHOENIX1 / 262180
Conditions: Degradation of Top2b and Top2a in Human by Dexrazoxane, Time Course and Degradation of Top2b in Human by Dexrazoxane, Effects of Dexrazoxane on Healthy Human
Keywords: Dexrazoxane, Topoisomerase 2b, Human, Doxorubicin cardio-toxicity, Cardio-oncology, Onco-cardiology, Prevention of cardio-toxicity by doxorubicin, Early administration of dexrazoxane
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: University of ArkansasUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: 14 Sep 2021 (actual)
Primary completion: 11 Jun 2024 (actual)
Study completion: 11 Jun 2025 (actual)
First posted: 29 Apr 2019 (actual)
Results: Posted 12 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5
Model description: Each subject will receive one dose of dexrazoxane.

Arm	Type	Receives
Dexrazoxane 100mg/m2	Experimental	Drug: Dexrazoxaneone dose of 100mg/m2 dexrazoxane
Dexrazoxane 200mg/m2	Experimental	Drug: Dexrazoxaneone dose of 200mg/m2 dexrazoxane
Dexrazoxane 300mg/m2	Experimental	Drug: Dexrazoxaneone dose of 300mg/m2 dexrazoxane
Dexrazoxane 400mg/m2	Experimental	Drug: Dexrazoxaneone dose of 400mg/m2 dexrazoxane
Dexrazoxane 500mg/m2	Experimental	Drug: Dexrazoxaneone dose of 500 mg/m2

Who may qualify

Ages: 18 to 65 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Women,
Age 18-65,
Not pregnant, Not currently breast feeding
No current illness,

Key exclusion criteria (3 listed)

Pregnancy, currently breast feeding
Current illness,
History of cardiac, or renal disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DexrazoxaneAlso: ZinecardOne dose of dexrazoxane	Drug	Dexrazoxane 100mg/m2, Dexrazoxane 200mg/m2, Dexrazoxane 300mg/m2, Dexrazoxane 400mg/m2, Dexrazoxane 500mg/m2

Primary outcome

Participants With 95% Reduction in Topoisomerase 2 b From Baseline
Time frame: 8 hours after dexrazoxane administration
Number of participants with 95% reduction in topoisomerase 2 b from baseline is reported in the Outcome Measure Data Table

Results and safety

Results posted to the registry on 12 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dexrazoxane 100mg/m2	5	5
Dexrazoxane 200mg/m2	5	5
Dexrazoxane 300mg/m2	5	5
Dexrazoxane 400mg/m2	5	5
Dexrazoxane 500mg/m2	5	5

Primary outcome: Participants With 95% Reduction in Topoisomerase 2 b From Baseline

Time frame: 8 hours after dexrazoxane administration. Count of participants. Unit: Participants

Measure	Dexrazoxane 100mg/m2 n = 4	Dexrazoxane 200mg/m2 n = 5	Dexrazoxane 300mg/m2 n = 5	Dexrazoxane 400mg/m2 n = 5	Dexrazoxane 500mg/m2 n = 5
Value	0	0	0	0	1

Adverse events

Time frame: The adverse event data were collected on the date of one dose dexrazoxane infusion, one day and two days after infusion, and one week after infusion. Some of the participants required a visit two weeks after one dose dexrazoxane infusion. Adverse event data were collected during the visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dexrazoxane 100mg/m2	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Dexrazoxane 200mg/m2	0 of 5 (0%)	1 of 5 (20%)	0 of 5
Dexrazoxane 300mg/m2	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Dexrazoxane 400mg/m2	0 of 5 (0%)	0 of 5 (0%)	0 of 5
Dexrazoxane 500mg/m2	0 of 5 (0%)	3 of 5 (60%)	0 of 5

Limitations and caveats (from the sponsor): In animal studies, Top2b expression can be directly measured in heart tissues; however, this is not feasible in human participants. Therefore, peripheral blood mononuclear cells were chosen as a surrogate tissue to assess Top2b degradation. Our study participants were adult women, so the dose-response curve and time course may not be applicable to the pediatric cancer population. Our study evaluates the dose-response and time course of dexrazoxane's effects on Top2a and Top2b expression.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 29145954Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. J Am Coll Cardiol. 2017 Nov 14;70(20):2536-2551. doi: 10.1016/j.jacc.2017.09.1096.
Background: PubMed 23104132Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012 Nov;18(11):1639-42. doi: 10.1038/nm.2919. Epub 2012 Oct 28.
Background: PubMed 23861158Lipshultz SE, Lipsitz SR, Kutok JL, Miller TL, Colan SD, Neuberg DS, Stevenson KE, Fleming MD, Sallan SE, Franco VI, Henkel JM, Asselin BL, Athale UH, Clavell LA, Michon B, Laverdiere C, Larsen E, Kelly KM, Silverman LB. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013 Oct 1;119(19):3555-62. doi: 10.1002/cncr.28256. Epub 2013 Jul 16.
Background: PubMed 6093249Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984 Oct 26;226(4673):466-8. doi: 10.1126/science.6093249.
Background: PubMed 14583452Olson LE, Bedja D, Alvey SJ, Cardounel AJ, Gabrielson KL, Reeves RH. Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1. Cancer Res. 2003 Oct 15;63(20):6602-6.
Background: PubMed 14597774Azuma Y, Arnaoutov A, Dasso M. SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol. 2003 Nov 10;163(3):477-87. doi: 10.1083/jcb.200304088. Epub 2003 Nov 3.
Background: PubMed 17875725Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, Liu LF. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007 Sep 15;67(18):8839-46. doi: 10.1158/0008-5472.CAN-07-1649.
Background: PubMed 9193323Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, Jones SE, Wadler S, Desai A, Vogel C, Speyer J, Mittelman A, Reddy S, Pendergrass K, Velez-Garcia E, Ewer MS, Bianchine JR, Gams RA. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997 Apr;15(4):1318-32. doi: 10.1200/JCO.1997.15.4.1318.
Background: PubMed 27371756Bluethmann SM, Mariotto AB, Rowland JH. Anticipating the "Silver Tsunami": Prevalence Trajectories and Comorbidity Burden among Older Cancer Survivors in the United States. Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1029-36. doi: 10.1158/1055-9965.EPI-16-0133.
Background: PubMed 29145955Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 2. J Am Coll Cardiol. 2017 Nov 14;70(20):2552-2565. doi: 10.1016/j.jacc.2017.09.1095.
Background: PubMed 24638000Armstrong GT, Kawashima T, Leisenring W, Stratton K, Stovall M, Hudson MM, Sklar CA, Robison LL, Oeffinger KC. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol. 2014 Apr 20;32(12):1218-27. doi: 10.1200/JCO.2013.51.1055. Epub 2014 Mar 17.
Background: PubMed 20159360Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K, Mabuchi K, Marks LB, Mettler FA, Pierce LJ, Trott KR, Yeh ET, Shore RE. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):656-65. doi: 10.1016/j.ijrobp.2009.09.064.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hui-Ming Chang, MD,MPH principal investigator

University of Arkansas

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants With 95% Reduction in Topoisomerase 2 b From Baseline (time frame: 8 hours after dexrazoxane administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03930680, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2025.