Neoplasms

Skin and Connective Tissue Diseases

All Conditions

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Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Quality of Life

Neuroendocrine Tumor

Neuroepithelioma

Bone Density Conservation Agents

Micronutrients

All Drugs and Chemicals

Vitamins

Vitamin D

Cholecalciferol

Ergocalciferols

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

Ergocalciferol

Vitamin D2

placebo and vitamin D

Jean Y Tang, MD, PhD

The purpose of this study is to determine the signaling pathways and changes in gene expression in melanocytes of subjects with a history of non-melanoma skin cancer who are exposed to oral vitamin D. If vitamin D is found to inhibit a signaling pathway involved in the development of melanoma such as BRAF, a protein involved in cell proliferation, then oral vitamin D could be explored further as a chemoprevention for melanoma skin cancer.

Background:

Vitamin D is an important hormone that has multiple genetic effects in different tissue types that are mediated by signaling through the vitamin D receptor.

Recent studies have shown that vitamin D signaling results in decreased innate immunity and increased adaptive immunity.

Multiple epidemiologic studies have suggested that vitamin D may play a role in decreasing the risk of developing multiple types of cancer, including skin cancer.

In the context of the relative success of novel immune-related therapies including PD1 inhibitors, which improves immuno-surveillance, and ipilimumab, which suppresses T cell response, there is increased promise for treatment strategies that activate innate immunity. This led us to ask the question of whether vitamin D could increase immune surveillance for melanoma via increased activity of the adaptive immune system.

Prior studies performed by our group and others have suggested that vitamin D may play a role in decreasing melanoma risk. An epidemiologic study from the Women's Health Initiative showed that women with a prior history of NMSC who received calcium and vitamin D supplementation had a lower risk of subsequently developing melanoma. At the same time, women with a lower serum vitamin D level had a higher risk of developing melanoma. Furthermore, a recent clinical study showed that vitamin D supplementation increases serum vitamin D levels and ultimately results in increased vitamin D receptor signaling in benign nevi.

Taken together, this findings led us to ask whether oral vitamin D supplementation could impact immune signaling in benign nevi and potentially underpin a theoretical chemo-preventive role for vitamin D in melanoma.

Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers

Results will be submitted to scientific journal for publication.

Normal cells have a complex series of molecular signals that allow communication between cells and to the cell nucleus. These signals work together to control one or more cell functions, such as cell division or cell death. Abnormal signaling activity caused by changes in gene expression can lead to cancer. An understanding of abnormal signaling, both in the tumor and in normal tissues, may lead to new therapies in cancer patients. We wish to identify changes in molecular signaling that occur in the development of melanoma that might be suppressed in benign nevi (moles) in response to vitamin D supplementation.

We utilized a prior gene expression study that compared malignant melanoma cells to benign nevi (moles) and identified over 2300 genes that were differentially regulated in melanoma compared to benign nevi. There were approximately 270 genes in our data set that showed changes in expression after vitamin D treatment. We wish to identify overlap between these two groups.

National Institutes of Health (NIH)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Stanford University

Associate Professor of Dermatology

4,000 IU oral vitamin D3

Vitamin D3: 4,000 IU oral vitamin D3

Arm A: Vitamin D

Arm B: Placebo

Placebo - subjects may cross over to vitamin D treatment after placebo treatment is complete

Total

Age, Continuous

Gender

United States

Region of Enrollment

Jean Y Tang MD PhD, assistant professor

All Patients Treated With Vitamin D3

Number of Genes That Showed Changes in Expression After Vitamin D Treatment

Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment

Vitamin D Toxicity

Incidence of Hypercalcemia for Vitamin D Toxicity

Placebo - patients may cross over to vitamin D3 treatment after placebo treatment

Overall Study

Spots Global Cancer Trial Database for placebo and vitamin d