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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL151993 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dexrazoxane 100mg/m2 | Experimental | one dose of 100mg/m2 dexrazoxane |
|
| Dexrazoxane 200mg/m2 | Experimental | one dose of 200mg/m2 dexrazoxane |
|
| Dexrazoxane 300mg/m2 | Experimental | one dose of 300mg/m2 dexrazoxane |
|
| Dexrazoxane 400mg/m2 | Experimental | one dose of 400mg/m2 dexrazoxane |
|
| Dexrazoxane 500mg/m2 | Experimental | one dose of 500 mg/m2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexrazoxane | Drug | One dose of dexrazoxane |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 8 hours after dexrazoxane administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hui-Ming Chang, MD,MPH | University of Arkansas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29145954 | Background | 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. | |
| 23104132 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dexrazoxane 100mg/m2 | one dose of 100mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| FG001 | Dexrazoxane 200mg/m2 | one dose of 200mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 13, 2023 | May 23, 2025 |
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Each subject will receive one dose of dexrazoxane.
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|
| 23861158 | Background | 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. |
| 6093249 | Background | 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. |
| 14583452 | Background | 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. |
| 14597774 | Background | 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. |
| 17875725 | Background | 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. |
| 9193323 | Background | 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. |
| 27371756 | Background | 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. |
| 29145955 | Background | 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. |
| 24638000 | Background | 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. |
| 20159360 | Background | 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. |
| 14564513 | Background | 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. |
| 27541948 | Background | 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. |
| 4290058 | Background | 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. |
| 496103 | Background | Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710-7. doi: 10.7326/0003-4819-91-5-710. |
| 6293697 | Background | Doroshow JH. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 1983 Feb;43(2):460-72. |
| 7350193 | Background | Doroshow JH, Locker GY, Myers CE. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest. 1980 Jan;65(1):128-35. doi: 10.1172/JCI109642. |
| 1997858 | Background | Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med. 1991 Mar 21;324(12):843-5. doi: 10.1056/NEJM199103213241210. No abstract available. |
| 18669466 | Background | Gianni L, Herman EH, Lipshultz SE, Minotti G, Sarvazyan N, Sawyer DB. Anthracycline cardiotoxicity: from bench to bedside. J Clin Oncol. 2008 Aug 1;26(22):3777-84. doi: 10.1200/JCO.2007.14.9401. |
| 3917371 | Background | Herman EH, Ferrans VJ, Myers CE, Van Vleet JF. Comparison of the effectiveness of (+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) and N-acetylcysteine in preventing chronic doxorubicin cardiotoxicity in beagles. Cancer Res. 1985 Jan;45(1):276-81. |
| 6340204 | Background | Myers C, Bonow R, Palmeri S, Jenkins J, Corden B, Locker G, Doroshow J, Epstein S. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin Oncol. 1983 Mar;10(1 Suppl 1):53-5. No abstract available. |
| 19010377 | Background | Martin E, Thougaard AV, Grauslund M, Jensen PB, Bjorkling F, Hasinoff BB, Tjornelund J, Sehested M, Jensen LH. Evaluation of the topoisomerase II-inactive bisdioxopiperazine ICRF-161 as a protectant against doxorubicin-induced cardiomyopathy. Toxicology. 2009 Jan 8;255(1-2):72-9. doi: 10.1016/j.tox.2008.10.011. Epub 2008 Oct 25. |
| 1380833 | Background | Capranico G, Tinelli S, Austin CA, Fisher ML, Zunino F. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta. 1992 Aug 17;1132(1):43-8. doi: 10.1016/0167-4781(92)90050-a. |
| 20448213 | Background | Wang J, Zhang S, Rabinovich B, Bidaut L, Soghomonyan S, Alauddin MM, Bankson JA, Shpall E, Willerson JT, Gelovani JG, Yeh ET. Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action. Circ Res. 2010 Jun 25;106(12):1904-11. doi: 10.1161/CIRCRESAHA.110.221762. Epub 2010 May 6. |
| 9768817 | Background | Hasinoff BB. Chemistry of dexrazoxane and analogues. Semin Oncol. 1998 Aug;25(4 Suppl 10):3-9. |
| 40317097 | Result | Chang HM, Hsu JY, Ahn C, Yeh ETH. Prevention of Heart Failure Induced by Doxorubicin with Early Administration of Dexrazoxane (PHOENIX Study): dose response and time course of dexrazoxane-induced degradation of topoisomerase 2b. Cardiooncology. 2025 May 2;11(1):42. doi: 10.1186/s40959-025-00339-0. |
| FG002 | Dexrazoxane 300mg/m2 | one dose of 300mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| FG003 | Dexrazoxane 400mg/m2 | one dose of 400mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| FG004 | Dexrazoxane 500mg/m2 | one dose of 500 mg/m2 Dexrazoxane: One dose of dexrazoxane |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dexrazoxane 100mg/m2 | one dose of 100mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| BG001 | Dexrazoxane 200mg/m2 | one dose of 200mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| BG002 | Dexrazoxane 300mg/m2 | one dose of 300mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| BG003 | Dexrazoxane 400mg/m2 | one dose of 400mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane |
| BG004 | Dexrazoxane 500mg/m2 | one dose of 500 mg/m2 Dexrazoxane: One dose of dexrazoxane |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Count of Participants | Participants | 8 hours after dexrazoxane administration |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dexrazoxane 100mg/m2 | one dose of 100mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane | 0 | 5 | 0 | 5 | 3 | 5 |
| EG001 | Dexrazoxane 200mg/m2 | one dose of 200mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane | 0 | 5 | 0 | 5 | 1 | 5 |
| EG002 | Dexrazoxane 300mg/m2 | one dose of 300mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane | 0 | 5 | 0 | 5 | 2 | 5 |
| EG003 | Dexrazoxane 400mg/m2 | one dose of 400mg/m2 dexrazoxane Dexrazoxane: One dose of dexrazoxane | 0 | 5 | 0 | 5 | 0 | 5 |
| EG004 | Dexrazoxane 500mg/m2 | one dose of 500 mg/m2 Dexrazoxane: One dose of dexrazoxane | 0 | 5 | 0 | 5 | 3 | 5 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| bruising | Skin and subcutaneous tissue disorders | NIH CTCAE | Systematic Assessment |
| |
| pain | Skin and subcutaneous tissue disorders | NIH CTCAE | Systematic Assessment |
| |
| anemia | Blood and lymphatic system disorders | NIH CTCAE | Systematic Assessment |
| |
| other | General disorders | NIH CTCAE | Systematic Assessment |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hui-Ming Chang, MD, MPH | University of Arkansas for Medical Sciences | 501-686-7575 | hchang@uams.edu |
| Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 16, 2023 | Jun 16, 2025 | ICF_001.pdf |
| ID | Term |
|---|---|
| D064730 | Dexrazoxane |
| ID | Term |
|---|---|
| D011929 | Razoxane |
| D054659 | Diketopiperazines |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Between 18 and 65 years |
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| >=65 years |
|
| Male |
|
| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|