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Breast CancerEarly Phase 1NCT02936999

Vitamin D Supplementation in Women With DCIS and/or LCIS

A Early Phase 1 study testing Cholecalciferol in people with Breast Cancer, run by Inova Health Care Services at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Cholecalciferol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
Aug 2016to Jan 2019
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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)

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Breast Cancer
Being tested
Cholecalciferol
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CholecalciferolDrug

    Also called Vitamin D3

    Cholecalciferol 100,000 IU followed by 4000 IU orally once daily for 30 days.

Study groups in NCT02936999
Study groupRoleWhat they receive
Vitamin D3ExperimentalPatients 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.
Receives: Drug: Cholecalciferol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days +/- 3 days from Day 1 of treatment

Secondary outcomes (4)
  1. 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.

    Measured: 28 days +/- 3 days from Day 1 of treatment

  2. 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.

    Measured: 28 days +/- 3 days from Day 1 of treatment

  3. 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.

    Measured: 28 days +/- 3 days from Day 1 of treatment

  4. 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.

    Measured: 28 days +/- 3 days from Day 1 of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionJan 2019
  4. Study completionJan 2019

Why it stopped: Terminated for lack of patient samples and funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02936999
Sponsor's protocol ID
16-2399
Status last verified
Oct 2020
First submitted
11 Oct 2016
Last updated
16 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 10576237
  • 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.

    PubMed 19689789
  • Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007 Sep;7(9):684-700. doi: 10.1038/nrc2196.

    PubMed 17721433
  • Espina V, Edmiston KH, Liotta LA. Non-enzymatic, serum-free tissue culture of pre-invasive breast lesions for spontaneous generation of mammospheres. J Vis Exp. 2014 Nov 8;(93):e51926. doi: 10.3791/51926.

    PubMed 25406584
  • Espina V, Liotta LA. What is the malignant nature of human ductal carcinoma in situ? Nat Rev Cancer. 2011 Jan;11(1):68-75. doi: 10.1038/nrc2950. Epub 2010 Dec 2.

    PubMed 21150936
  • Espina V, Mariani BD, Gallagher RI, Tran K, Banks S, Wiedemann J, Huryk H, Mueller C, Adamo L, Deng J, Petricoin EF, Pastore L, Zaman S, Menezes G, Mize J, Johal J, Edmiston K, Liotta LA. Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival. PLoS One. 2010 Apr 20;5(4):e10240. doi: 10.1371/journal.pone.0010240.

    PubMed 20421921
  • 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.

    PubMed 15015703
  • Esserman L, Sepucha K, Ozanne E, Hwang ES. Applying the neoadjuvant paradigm to ductal carcinoma in situ. Ann Surg Oncol. 2004 Jan;11(1 Suppl):28S-36S. doi: 10.1007/BF02524793.

    PubMed 15015707
  • Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88. doi: 10.1093/jnci/90.18.1371.

    PubMed 9747868
  • Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011 Mar 15;128(6):1414-24. doi: 10.1002/ijc.25439.

    PubMed 20473927
  • 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.

    PubMed 17214797
  • Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. doi: 10.1093/ajcn/85.1.6.

    PubMed 17209171
  • Alipour S, Hadji M, Hosseini L, Omranipour R, Saberi A, Seifollahi A, Bayani L, Shirzad N. Levels of serum 25-hydroxy-vitamin d in benign and malignant breast masses. Asian Pac J Cancer Prev. 2014;15(1):129-32. doi: 10.7314/apjcp.2014.15.1.129.

    PubMed 24528013
  • Hird RB, Chang A, Cimmino V, Diehl K, Sabel M, Kleer C, Helvie M, Schott A, Young J, Hayes D, Newman L. Impact of estrogen receptor expression and other clinicopathologic features on tamoxifen use in ductal carcinoma in situ. Cancer. 2006 May 15;106(10):2113-8. doi: 10.1002/cncr.21873.

    PubMed 16596655
  • Hwang ES, Esserman L. Neoadjuvant hormonal therapy for ductal carcinoma in situ: trial design and preliminary results. Ann Surg Oncol. 2004 Jan;11(1 Suppl):37S-43S. doi: 10.1007/BF02524794.

    PubMed 15015708

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Cholecalciferol in people with Breast Cancer, run by Inova Health Care Services at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ki 67 Measured (time frame: 28 days +/- 3 days from Day 1 of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02936999, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2020.

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