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Terminated for lack of patient samples and funding
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin D3 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholecalciferol | Drug | Cholecalciferol 100,000 IU followed by 4000 IU orally once daily for 30 days. |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mary Wilkinson, MD | Inova Schar Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Inova Schar Cancer Institute | Fairfax | Virginia | 22031 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10576237 | Background | Bernardes JR Jr, Nonogaki S, Seixas MT, Rodrigues de Lima G, Baracat EC, Gebrim LH. Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue. Int J Gynaecol Obstet. 1999 Oct;67(1):33-8. doi: 10.1016/s0020-7292(99)00092-2. | |
| 19689789 | Background | Chen YY, DeVries S, Anderson J, Lessing J, Swain R, Chin K, Shim V, Esserman LJ, Waldman FM, Hwang ES. Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ. BMC Cancer. 2009 Aug 18;9:285. doi: 10.1186/1471-2407-9-285. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Group | Patients will receive 100,000 IU PO loading dose at Day 1. The loading dose must be administered to the patient at the investigator's site. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The study was terminated due to low enrollment and lack of funding; therefore no data were collected. | Posted | 28 days +/- 3 days from Day 1 of treatment |
|
|
Clinical Assessment and adverse event evaluation will be done at Day 14, Day 21, and on the Post-Op visit on the study
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Group | Patients will receive 100,000 IU PO loading dose at Day 1. The loading dose must be administered to the patient at the investigator's site. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Regulatory Research Coordinator | Inova Health Services | (571) 472-0239 | elizabeth.gebregeorgis@inova.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 21, 2016 | Nov 13, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| 28 days +/- 3 days from Day 1 of treatment |
| 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 |
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| 15015703 | Background | Esserman L. Neoadjuvant chemotherapy for primary breast cancer: lessons learned and opportunities to optimize therapy. Ann Surg Oncol. 2004 Jan;11(1 Suppl):3S-8S. doi: 10.1007/BF02524789. No abstract available. |
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| 17214797 | Background | Gonzalez RJ, Buzdar AU, Fraser Symmans W, Yen TW, Broglio KR, Lucci A, Esteva FJ, Yin G, Kuerer HM. Novel clinical trial designs for treatment of ductal carcinoma in situ of the breast with trastuzumab (herceptin). Breast J. 2007 Jan-Feb;13(1):72-5. doi: 10.1111/j.1524-4741.2006.00366.x. |
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| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Counts |
|---|
| Participants |
|
| 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. | The study was terminated due to low enrollment and lack of funding therefore no data were collected. | Posted | 28 days +/- 3 days from Day 1 of treatment |
|
|
| 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. | The study was terminated due to low enrollment and lack of funding; therefore no data were collected. | Posted | 28 days +/- 3 days from Day 1 of treatment |
|
|
| 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. | The study was terminated due to low enrollment and lack of funding; therefore no data were collected. | Posted | 28 days +/- 3 days from Day 1 of treatment |
|
|
| 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. | The study was terminated due to low enrollment and lack of funding; therefore no data were collected. | Posted | 28 days +/- 3 days from Day 1 of treatment |
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
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| D017437 |
| Skin and Connective Tissue Diseases |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |