Breast Cancer
Conditions
Brief summary
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
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.
Interventions
DRUGCholecalciferol
Cholecalciferol 100,000 IU followed by 4000 IU orally once daily for 30 days.
Sponsors
Inova Health Care Services
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ki 67 Measured | 28 days +/- 3 days from Day 1 of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of Proteins of the Autophagy Pathway, LC3B | 28 days +/- 3 days from Day 1 of treatment | 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. |
| Levels of Proteins of the Autophagy Pathway, ATG7 | 28 days +/- 3 days from Day 1 of treatment | 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. |
| Levels of the Calcium Transport Proteins, PMCA2 | 28 days +/- 3 days from Day 1 of treatment | 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. |
| HER2 Localization | 28 days +/- 3 days from Day 1 of treatment | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Patients will receive 100,000IU PO loading dose at Day 1. The loading dose must be administered to the patient at the investigator's site. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: 28 days +/- 3 days from Day 1 of treatment
Population: The study was terminated due to low enrollment and lack of funding; therefore no data were collected.
Secondary
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.
Time frame: 28 days +/- 3 days from Day 1 of treatment
Population: The study was terminated due to low enrollment and lack of funding; therefore no data were collected.
Secondary
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.
Time frame: 28 days +/- 3 days from Day 1 of treatment
Population: The study was terminated due to low enrollment and lack of funding; therefore no data were collected.
Secondary
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.
Time frame: 28 days +/- 3 days from Day 1 of treatment
Population: The study was terminated due to low enrollment and lack of funding therefore no data were collected.
Secondary
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.
Time frame: 28 days +/- 3 days from Day 1 of treatment
Population: The study was terminated due to low enrollment and lack of funding; therefore no data were collected.