Vitamin D Supplementation in Women With DCIS and/or LCIS

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and usefulness of oral Vitamin D supplementation in subjects with in situ carcinoma. More specifically, this study is being done to (1) understand the effect of Vitamin D supplementation on behavior of breast cancer cells and (2) the development of invasive breast cancer disease.

Detailed Description
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In vitro, calcitriol, the most potent metabolite of vitamin D, inhibits a variety of cellular pathways that promote cell proliferation and survival. Vitamin D has been shown to reduce the growth of breast cancer precursor cells in cell culture studies. In animal models Vitamin D has been shown to prevent the growth and progression of transplanted cell lines MCF710A, which is a model of pre-invasive cancer. Serum Vitamin D level deficiency correlates with an increased risk of breast cancer, and reduced survival of breast cancer patients. Vitamin D is also recognized to have effects on immune cell function and autoimmunity. The safety profile of oral Vitamin D, and its metabolite calcitriol, was well established for moderate term and acute therapy worldwide. Potential additional primary and secondary benefits of vitamin D are a) the suppression of carcinogen-induced transformation or progression of breast epithelium, and b) the enhancement of innate immune defense of pre-invasive breast cancer lesions, and c) its qualification as a combination therapy when combined with other neoadjuvant therapies for DCIS. Patients who have been diagnosed by core biopsy with carcinoma in situ, ductal or lobular, will be evaluated for vitamin d supplementation. Patients with vitamin d levels less than 50 will be eligible for participation. They will receive a one month (30 days) schedule of vitamin D supplementation and then proceed with the standard of care of surgical excision. Immunohistochemistry studies will be performed on the diagnostic core biopsy and the surgical specimen to evaluate the impact of vitamin d supplementation on: the proliferative index-ki67, proliferative marker- PCNA, proteins of the autophagy pathway (LC3B, ATG7), her2 localization, and levels of PMCA2 - calcium efflux channel.

Official Title
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An Exploratory Pilot Study of Vitamin D Supplementation in Women With DCIS and/or LCIS

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a tissue diagnosis of lobular carcinoma in situ or ductal carcinoma in situ and being scheduled to undergo excision of their cancer Subjects must be female at least 18 years of age Subjects must have a signed consent Normal liver function based on (total bilirubin and AST <1.5 x Upper Limit of Normal) Serum creatinine < 2.0 mg/dL Serum 25 (OH) D levels < 50 ng/ml Calcium within the normal range (8.5-10.2 mg/dL) ECOG performance status 0-2 Are able to swallow and retain oral medication Subjects should be willing to abstain from use of hormonal therapies (e.g. hormone replacement therapy, oral contraceptive pills, hormone-containing IUDs, and E-string) Exclusion Criteria: Patient desires not to participate in the study Inability to give consent Current use of hormone-containing forms of birth control such as implants (i.e. Norplants, or injectables (i.e. depo-provera) Currently lactating Patients with history of renal or hepatic insufficiency Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication History of granulomatous disease such as tuberculosis or sarcoidosis History of Vitamin D supplementation > 2000 IU/day within the last 2 months History of hypoparathyroidism

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Patients will be dispensed cholecalciferol, 32 capsules/bottle of 1cap/4000 IU PO QD on Day 1 visit to take home. Bottle must be labeled with instructions on how to take the drug and the assigned patient ID number. Patients will be instructed to take 1 capsule per day, with water, for 29 days using the dispensed study bottle. They will be instructed to stop taking their daily vitamin D3 dose after 30 days of treatment. A study drug diary will be provided at Day 1 visit and patients will be instructed to complete the study drug diary daily from Day 2 to Day 30. Patient's report of vitamin-D3 intake from the diary must be reconciled against the number of capsules returned at Day 30 visit. | Drug: Cholecalciferol<br>* Cholecalciferol 100,000 IU followed by 4000 IU orally once daily for 30 days.<br>* Other names: Vitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ki 67 Measured | The proliferation index measured by Ki67 will be described for both baseline (pre) and surgical (post) vitamin D supplementation. A paired t-test or the non-parametric Wilcoxon signed-rank test will be used when appropriate to compare patients' outcome between baseline and after-treatment. | 28 days +/- 3 days from Day 1 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Proteins of the Autophagy Pathway, ATG7 | Descriptive statistics (N, mean, median, Min, Max, STD for continuous variables, and N, proportion for categorical variables) will be used to summarize patients' demographics as well as lab results. . A paired t-test or the non-parametric Wilcoxon signed-rank test will be used when appropriate to compare patients' outcome between baseline and after-treatment. A p-value of <0.05 will be considered statistically significant. | 28 days +/- 3 days from Day 1 of treatment | 
| Levels of the Calcium Transport Proteins, PMCA2 | Descriptive statistics (N, mean, median, Min, Max, STD for continuous variables, and N, proportion for categorical variables) will be used to summarize patients' demographics as well as lab results. A paired t-test or the non-parametric Wilcoxon signed-rank test will be used when appropriate to compare patients' outcome between baseline and after-treatment. A p-value of <0.05 will be considered statistically significant. | 28 days +/- 3 days from Day 1 of treatment | 
| HER2 Localization | Descriptive statistics (N, mean, median, Min, Max, STD for continuous variables, and N, proportion for categorical variables) will be used to summarize patients' demographics as well as lab results. A paired t-test or the non-parametric Wilcoxon signed-rank test will be used when appropriate to compare patients' outcome between baseline and after-treatment. A p-value of <0.05 will be considered statistically significant. | 28 days +/- 3 days from Day 1 of treatment | 
| Levels of Proteins of the Autophagy Pathway, LC3B | Descriptive statistics (N, mean, median, Min, Max, STD for continuous variables, and N, proportion for categorical variables) will be used to summarize patients' demographics as well as lab results. . A paired t-test or the non-parametric Wilcoxon signed-rank test will be used when appropriate to compare patients' outcome between baseline and after-treatment. A p-value of <0.05 will be considered statistically significant. | 28 days +/- 3 days from Day 1 of treatment |