Clinical Trials Logo
  1. Home
  2. Healthy
  3. NCT03930680
  4. Details
NCT03930680 Clinical Trial

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

Healthy Clinical Trial

— PHOENIX1  

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

Clinical Trial Details — Status: Recruiting

Administrative data
NCT number NCT03930680
Other study ID # 262180
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 14, 2021
Est. completion date October 31, 2025

Study information
Verified date February 2024
Source University of Arkansas
Contact Hui-Ming Chang, MD,MPH
Phone 501-686-7575
Email hchang@uams.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility
Status Recruiting
Enrollment 25
Est. completion date October 31, 2025
Est. primary completion date October 31, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - Women, - Age 18-65, - Not pregnant, Not currently breast feeding - No current illness, Exclusion Criteria: - Pregnancy, currently breast feeding - Current illness, - History of cardiac, or renal disease

Study Design

Related Conditions & MeSH terms

Intervention

Drug:
• Dexrazoxane
One dose of dexrazoxane

Locations
Country Name City State
United States University of Arkansas for Medical Sciences Little Rock Arkansas

Sponsors (1)
Lead Sponsor Collaborator
University of Arkansas

Country where clinical trial is conducted

United States, 

References & Publications (26)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Am Coll Cardiol. 2018 Feb 6;71(5):587. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med. 1991 Mar 21;324(12):843-5. doi: 10.1056/NEJM199103213241210. No abstract available. — View Citation

Doroshow JH. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 1983 Feb;43(2):460-72. — View Citation

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. — View Citation

Hasinoff BB. Chemistry of dexrazoxane and analogues. Semin Oncol. 1998 Aug;25(4 Suppl 10):3-9. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome
Type Measure Description Time frame Safety issue
Primary Degradation of Topoisomerase 2 b Topoisomerase 2 b degradation to less than 15 percent of baseline level in human blood of 5 volunteers. 48 hours after administration
See also
  Status Clinical Trial Phase
Recruiting NCT06052553 - A Study of TopSpin360 Training Device N/A
Completed NCT05511077 - Biomarkers of Oat Product Intake: The BiOAT Marker Study N/A
Recruiting NCT04632485 - Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
Completed NCT05931237 - Cranberry Flavan-3-ols Consumption and Gut Microbiota in Healthy Adults N/A
Completed NCT04527718 - Study of the Safety, Tolerability and Pharmacokinetics of 611 in Adult Healthy Volunteers Phase 1
Terminated NCT04556032 - Effects of Ergothioneine on Cognition, Mood, and Sleep in Healthy Adult Men and Women N/A
Completed NCT04065295 - A Study to Test How Well Healthy Men Tolerate Different Doses of BI 1356225 Phase 1
Completed NCT04107441 - AX-8 Drug Safety, Tolerability and Plasma Levels in Healthy Subjects Phase 1
Completed NCT04998695 - Health Effects of Consuming Olive Pomace Oil N/A
Completed NCT01442831 - Evaluate the Absorption, Metabolism, And Excretion Of Orally Administered [14C] TR 701 In Healthy Adult Male Subjects Phase 1
Terminated NCT05934942 - A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood Phase 1
Recruiting NCT05525845 - Studying the Hedonic and Homeostatic Regulation of Food Intake Using Functional MRI N/A
Completed NCT05515328 - A Study in Healthy Men to Test How BI 685509 is Processed in the Body Phase 1
Completed NCT04967157 - Cognitive Effects of Citicoline on Attention in Healthy Men and Women N/A
Completed NCT05030857 - Drug-drug Interaction and Food-effect Study With GLPG4716 and Midazolam in Healthy Subjects Phase 1
Recruiting NCT04714294 - Evaluate the Safety, Tolerability and Pharmacokinetics Characteristics of HPP737 in Healthy Volunteers Phase 1
Recruiting NCT04494269 - A Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls Phase 1
Completed NCT04539756 - Writing Activities and Emotions N/A
Recruiting NCT04098510 - Concentration of MitoQ in Human Skeletal Muscle N/A
Completed NCT03308110 - Bioavailability and Food Effect Study of Two Formulations of PF-06650833 Phase 1