MELABLOCK: A Clinical Trial on the Efficacy and Safety of Propranolol 80 mg in Melanoma Patients

Summary

The effectiveness of propranolol in infantile hemangiomas, the apparent better response to propranolol in breast cancer and the use of propranolol in a proportion of patients who did not develop melanoma recurrence suggested to use this unselective β---blocker to test the study hypothesis. The investigators propose a randomized double---blind placebo---controlled clinical trial (RTC) to evaluate whether the treatment with propranolol 80 mgR/die reduce the risk of CMM recurrence and mortality. Patients with resected stage II/IIIA CMM will be recruited in various Centers in Italy. Participants will be randomly assigned to propranolol treatment or placebo (1:1 ratio), treated for at least 1 year and followed for 2 years. Recruitment will proceed simultaneously at the different Centers, and will be completed in 2 years. The primary outcome of the entire trial will be, however, estimated by assessing a reduction in overall mortality at five years. The investigators will also evaluate general CMM recurrence and CMM specific mortality.

Timeline

Start

2017-06

Primary completion

2019-06

Completion

2022-06

Publications

• Background Aronow WS. Current role of beta-blockers in the treatment of hypertension. Expert Opin Pharmacother. 2010 Nov;11(16):2599-607. doi: 10.1517/14656566.2010.482561. Epub 2010 Apr 28.
• Background Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer mortality: a population- based study. J Clin Oncol. 2011 Jul 1;29(19):2635-44. doi: 10.1200/JCO.2010.33.5422. Epub 2011 May 31.
• Background Bielecka-Dabrowa A, Aronow WS, Rysz J, Banach M. Current place of beta-blockers in the treatment of hypertension. Curr Vasc Pharmacol. 2010 Nov;8(6):733-41. doi: 10.2174/157016110793563861.
• Background Chen JM, Heran BS, Perez MI, Wright JM. Blood pressure lowering efficacy of beta-blockers as second-line therapy for primary hypertension. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD007185. doi: 10.1002/14651858.CD007185.pub2.
• Background Cruickshank JM. Are we misunderstanding beta-blockers. Int J Cardiol. 2007 Aug 9;120(1):10-27. doi: 10.1016/j.ijcard.2007.01.069. Epub 2007 Apr 12.
• Background De Giorgi V, Gandini S, Grazzini M, Benemei S, Marchionni N, Geppetti P. Effect of beta-blockers and other antihypertensive drugs on the risk of melanoma recurrence and death. Mayo Clin Proc. 2013 Nov;88(11):1196-203. doi: 10.1016/j.mayocp.2013.09.001.
• Background De Giorgi V, Grazzini M, Gandini S, Benemei S, Lotti T, Marchionni N, Geppetti P. Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med. 2011 Apr 25;171(8):779-81. doi: 10.1001/archinternmed.2011.131.
• Background Lamy S, Lachambre MP, Lord-Dufour S, Beliveau R. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells. Vascul Pharmacol. 2010 Nov-Dec;53(5-6):200-8. doi: 10.1016/j.vph.2010.08.002. Epub 2010 Aug 20.
• Background Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.
• Background Lemeshow S, Sorensen HT, Phillips G, Yang EV, Antonsen S, Riis AH, Lesinski GB, Jackson R, Glaser R. beta-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2273-9. doi: 10.1158/1055-9965.EPI-11-0249. Epub 2011 Sep 20.
• Background Lyons KE, Pahwa R. Pharmacotherapy of essential tremor : an overview of existing and upcoming agents. CNS Drugs. 2008;22(12):1037-45. doi: 10.2165/0023210-200822120-00006.
• Background Miller AJ, Mihm MC Jr. Melanoma. N Engl J Med. 2006 Jul 6;355(1):51-65. doi: 10.1056/NEJMra052166. No abstract available.
• Background Ozeki M, Fukao T, Kondo N. Propranolol for intractable diffuse lymphangiomatosis. N Engl J Med. 2011 Apr 7;364(14):1380-2. doi: 10.1056/NEJMc1013217. No abstract available.
• Background Perron L, Bairati I, Harel F, Meyer F. Antihypertensive drug use and the risk of prostate cancer (Canada). Cancer Causes Control. 2004 Aug;15(6):535-41. doi: 10.1023/B:CACO.0000036152.58271.5e.
• Background Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004 Sep 2;351(10):998-1012. doi: 10.1056/NEJMra041245. No abstract available.
• Background Williams B. Beta-blockers and the treatment of hypertension. J Hypertens. 2007 Jul;25(7):1351-3. doi: 10.1097/HJH.0b013e328182266a. No abstract available.
• Background Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, Volmink J. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002003. doi: 10.1002/14651858.CD002003.pub2.

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