A clinical trial is a way to evaluate a new drug or treatment and cancer clinical trials are conducted to answer questions about treating cancer, diagnosing cancer, preventing cancer or managing symptoms of cancer or effects of treatment. Penn State Cancer Institute has a long history of excellence in conducting clinical research and clinical trials. Through clinical trials, we have helped to advance the treatment of a number of cancers. We take great care to insure the scientific integrity and ethical conduct of trials.
This web site provides general information on clinical trials, and it provides links to active clinical trials at our Cancer Institute. It also includes a section of helpful information for our investigators. We provide information about support available through Penn State Cancer Institute Clinical Trials Office and we provide templates for protocol development. Additionally, links for submission forms for the Scientific Review Committee and the Data and Safety Monitoring Board are available within this web site. We hope you find our web site useful.
Recent Advances in Vitamin D Analog Development for Cancer
Andrew Yeich with Allison Blumling, Nadine Crone and Robin Taylor Wilson
Research into the health effects of Vitamin D first began in the early 1900’s when it was discovered that the vitamin prevented rickets when introduced through the diet. Low concentrations of the major circulating form (25(OH)D) has been associated with a wide variety of ailments, including certain cancers. However, the Institute of Medicine in its comprehensive review of over 1000 studies could not conclusively link vitamin D to cancer risk (IOM, 2010). Other studies suggest that high concentrations of 25(OH)D are also associated with increased mortality for stroke and heart disease (Durup, 2015).
While the role of vitamin D in bone health is most clearly established, studies over the past decade suggest anti-tumor properties of the active metabolite (1a,25(OH)2D3), which is produced primarily in the kidney. A major role includes apopotosis - or the induction of the cell death program in cancer cells. Due to its side-effects including hypercalcemia and hypercalcuiria, which can weaken bones, cause kidney stones, and interfere with heart and brain function; the active form (1a,25(OH)2D3) has not been considered a viable therapy option.
Therefore, a number of vitamin D compounds have been under development with the hope of beneficial therapeutic effects without the calcemic side-effects. One such compound is MART-10. Chiang et al. recently have shown experimental evidence that MART-10 slowed the metastatic growth of thyroid cancer cells (Chiang, 2015). In humans, thyroid cancer is highly metastatic and no effective treatment is currently available. Another study in animals found that MART-10 prevented prostate cancer cell invasion (Iglesias-Gato, 2011). MART-10 also reduced angiogenesis (new blood vessel growth) induced by the vascular endothelial growth factor A (VEGF-A) - a protein considered to be the main, dominant inducer of blood vessel growth (Chiang, 2016).
By preventing tumorous cells from inducing the growth of new blood vessels, compounds like MART-10 could greatly reduce the frequency of a variety of cancers. This, along with other anti-proliferative and pro-apoptotic effects of vitamin D, suggest one promising avenue for future treatments. Currently, there are no therapeutic trials of MART-10 in cancer patients. In the meantime, the Wilson Lab at Penn State is studying how the balance of circulating vitamin D metabolites and the vitamin D binding protein may better predict cancer risk.
- Chiang KC, Kuo SF, Chen CH, Ng S, Lin SF, Yeh CN, Chen LW, Takano M, Chen TC, Juang HH, Kittaka A, Lin JD, Pang JH. MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential. Cancer Lett 369(1):76-85, 2015. doi: 10.1016/j.canlet.2015.07.024.
- Chiang KC, Sun CC, Chen MH, Huang CY, Hsu JT, Yeh TS, Chen LW, Kuo SF, Juang HH, Takano M, Kittaka A, Chen TC, Yeh CN, Pang JH. MART-10, the new brand of 1a,25(OH)2D3 analog, is a potent anti-angiogenic agent in vivo and in vitro. J Steroid Biochem Mol Biol 155(Pt A):26-34, 2016. doi: 10.1016/j.jsbmb.2015.09.022.
- Durup D, Jørgensen HL, Christensen J, Tjønneland A, et al. A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study J Clin Endocrinol Metab 100(6): 2339–2346, 2015.
- Iglesias-Gato D, Zheng S, Flanagan JN, Jiang L, Kittaka A, Sakaki T, Yamamoto K, Itoh T, Lebrasseur NK, Norstedt G, Chen TC. Substitution at carbon 2 of 19-nor-1a,25-dihydroxyvitamin D3 with 3-hydroxypropyl group generates an analogue with enhanced chemotherapeutic potency in PC-3 prostate cancer cells. J Steroid Biochem Mol Biol 127(3-5):269-75, 2011. doi: 10.1016/j.jsbmb.2011.08.010.
- Institute of Medicine (IOM) Dietary Reference Intakes for Calcium and Vitamin D (Washington, DC: THE National Academies Press), 2010.
Colon Cancer and Vitamin D: Jury still out - new study results due 2017
The Women's Health Initiative (WHI) Calcium/Vitamin D Supplementation Study is the largest randomized intervention trial of vitamin D to date. A total of 36,282 post- menopausal women between the ages of 50-79 with anticipated three year survival were received either 1000 mg of elemental calcium plus 400 IU vitamin D3 daily or placebo. The results after seven and eleven years of follow-up showed that vitamin D and calcium supplementation had no effect on the incidence of colorectal cancer among postmenopausal women (1, 2). However, other studies have suggested that because women in the vitamin D trial also participated in the post-menopausal hormone therapy trials, results from the vitamin D and calcium trial may have been affected (3). A new study (VITAL), due in 2017, will be looking at these outcomes in depth. VITAL is a study in 25,875 men and women across the U.S. investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. (www.vitalstudy.org).
- Wactawski-Wende et al. 2006. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 354(7):684-96. PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/16481636
- Cauley et al. 2013. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative. J Women's Health. 22(11):915-29 PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/24131320
- Ding EL, Mehta S, Fawzi WW, Giovannucci EL. 2008. Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: reanalysis of Women's Health Initiative Randomized Trial. Int J Cancer. 122(8): 1690-4. PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/18092326