- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03930680
Prevention of Heart Failure Induced by Doxorubicin With Early Administration of Dexrazoxane (PHOENIX1)
February 15, 2024 updated by: University of Arkansas
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.
Study Overview
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
Study Type
Interventional
Enrollment (Estimated)
25
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Hui-Ming Chang, MD,MPH
- Phone Number: 501-686-7575
- Email: hchang@uams.edu
Study Contact Backup
- Name: Edward TH Yeh, MD
- Phone Number: 501-686-7045
- Email: eyeh@uams.edu
Study Locations
-
-
Arkansas
-
Little Rock, Arkansas, United States, 72205
- Recruiting
- University of Arkansas for Medical Sciences
-
Contact:
- Hui-Ming Chang, MD, MPH
- Phone Number: 501-686-7575
- Email: hchang@uams.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dexrazoxane 100mg/m2
one dose of 100mg/m2 dexrazoxane
|
One dose of dexrazoxane
Other Names:
|
Experimental: Dexrazoxane 200mg/m2
one dose of 200mg/m2 dexrazoxane
|
One dose of dexrazoxane
Other Names:
|
Experimental: Dexrazoxane 300mg/m2
one dose of 300mg/m2 dexrazoxane
|
One dose of dexrazoxane
Other Names:
|
Experimental: Dexrazoxane 400mg/m2
one dose of 400mg/m2 dexrazoxane
|
One dose of dexrazoxane
Other Names:
|
Experimental: Dexrazoxane 500mg/m2
one dose of 500 mg/m2
|
One dose of dexrazoxane
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Degradation of Topoisomerase 2 b
Time Frame: 48 hours after administration
|
Topoisomerase 2 b degradation to less than 15 percent of baseline level in human blood of 5 volunteers.
|
48 hours after administration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Hui-Ming Chang, MD,MPH, University of Arkansas
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Doroshow JH. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 1983 Feb;43(2):460-72.
- 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.
- Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med. 1991 Mar 21;324(12):843-5. doi: 10.1056/NEJM199103213241210. No abstract available.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Hasinoff BB. Chemistry of dexrazoxane and analogues. Semin Oncol. 1998 Aug;25(4 Suppl 10):3-9.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 14, 2021
Primary Completion (Estimated)
October 31, 2024
Study Completion (Estimated)
October 31, 2025
Study Registration Dates
First Submitted
April 25, 2019
First Submitted That Met QC Criteria
April 26, 2019
First Posted (Actual)
April 29, 2019
Study Record Updates
Last Update Posted (Actual)
February 16, 2024
Last Update Submitted That Met QC Criteria
February 15, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Heart Failure
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Cardiotonic Agents
- Dexrazoxane
- Razoxane
Other Study ID Numbers
- 262180
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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