Vitamin D treatment for melanoma
Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDME).
Why this trial?
Cutaneous malignant melanoma is the most common lethal skin disease worldwide. Although it only accounts for 4% of all malignant tumours of the skin, it is responsible for 80% of the skin cancer-related deaths. While early stage malignant melanoma can be cured, late stage (metastatic) melanoma decreases the chance of survival markedly because of its resistance to chemotherapy.
There is a high need to improve the outcome of malignant melanoma of the skin in terms of years of life lost. Improvement of melanoma outcomes could be achieved by diagnosing the tumour in an earlier stage and by decreasing the chance of relapse after surgery.
Why this drug?
Vitamin D has a good safety profile and is in some cases even recommended as food supplement (Norman and Bouillon et al 2010).
Secondly, the skin is an important target site for the actions of vitamin D. Skin cells synthesise the hormonally active vitamin D metabolite (1,25(OH)2D3), and there is evidence that 1,25(OH)2D3 can protect skin cells from UV damage (De Haes 2005; Gupta 2007).
Thirdly, epidemiological evidence for a possible protective influence of sunlight/vitamin D on melanoma risk is suggested by studies showing lower- than-expected incidence in people with outdoor occupations, which could reflect a level of protection afforded by their greater reserves of vitamin D (Gandini, 2009).
Fourthly, the active metabolite of vitamin D (1,25(OH)2D3) demonstrates relevant anti-cancer effects on melanoma cells, not only antiproliferative, pro-differentiating and proapoptotic effects, but also inhibitory effects on tumour invasion and metastasis (Osborne 2002 & Egan 2009). Vitamin D levels may have a protective effect on malignant melanoma outcome as well (Nürnberg 2009 & Newton Bishop 2009).
Scientific proof of a notable therapeutic effect of the well-tolerated and cheap vitamin D will be a major step forward in the battle against malignant melanoma.
This is a phase III, double-blind, randomised, placebo-controlled trial of high-dose vitamin D3 (cholecalciferol) in patients with stage IB to III cutaneous melanoma. 500 patients will be recruited and treated in 3 Belgian and one Hungarian centre.
The primary objective is to assess whether vitamin D3 supplementation, in the follow-up period after diagnosis and surgery of the primary tumour, has a protective effect regarding relapse of cutaneous malignant melanoma. Stage IB to III cutaneous melanoma patients will receive optimal standard of care and will be randomised between additional cholecalciferol (100,000 IE) or placebo. Study medication will be continued for a maximum of 3.5 years, or until relapse.
- Prof. Marjan Garmyn, Dermatology Dept., University Hospital Leuven, Leuven, Belgium
- University Hospital Leuven, Leuven, Belgium
More info on clinicaltrials.gov: NCT01748448
Balch, C.M., et al. (2009) Final version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol., 27(36):6199-206. doi:10.1200/JCO.2009.23.4799
De Haes, P., et al. (2005). 1,25-Dihydroxyvitamin D3 and analogues protect primary human keratinocytes against UVB-induced DNA damage. J Photochem Photobiol B, 78(2): 141-8. doi:10.1016/j.jphotobiol.2004.09.010
Egan, K.M. (2009). Vitamin D and melanoma. Ann Epidemiol., 19(7),455-61. doi:10.1016/j.annepidem.2009.01.005
Gandini, S., et al. (2009). Vitamin D and skin cancer: a meta-analysis. Eur J Cancer, 45(4), 634-41. doi: 10.1016/j.ejca.2008.10.003
Miller, A.J., et al. (2006). Melanoma. N Engl J Med., 355(1):51-65. doi:10.1056/NEJMra052166
Author: Kristine Beckers (Trial Manager)
Last updated: June 2018.