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Effect of High Dose Vitamin D on Cancer Biomarkers and Breast Cancer Tumors

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ClinicalTrials.gov Identifier: NCT02856503
Recruitment Status : Withdrawn (Lack of Funding)
First Posted : August 5, 2016
Last Update Posted : January 18, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Avisar, University of Miami

Brief Summary:
High-doses of Vitamin D (VD) may be used as targeted therapy against breast cancer. The investigators will assess the effect of high dose VD on the following biomarkers in the breast cancer cells: VDR, estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 2 (Her2/neu), androgen receptor (AR), as well as epidermal growth factor receptor 1 (EGFR) and Ki-67, as markers of proliferation, and E-cadherin, a marker of invasion and metastasis.

Condition or disease Intervention/treatment Phase
Breast Cancer Invasive Breast Carcinoma Ductal Carcinoma In-situ Drug: Vitamin D3 Phase 1 Phase 2

Detailed Description:

This is a phase I/II open-label, non-randomized study. In phase I, a fixed weekly course of oral high-dose Vitamin D (VD) is planned for either 3, 4 or 5 weeks; patients will be sequentially enrolled into 3 groups (A, B or C respectively) in a manner such that no more than two patients may have treatment-limiting toxicities (TLTs).

After the group with the optimal duration of VD therapy to achieve a "favorable response" is determined, phase II will begin enrollment.

Patients must be scheduled to have surgery performed within 2- weeks of the last dose of VD.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study Evaluating Safety and Effects of Preoperative High-Dose Vitamin D on the Receptors, Biomarkers and Pathological Characteristics of High Grade DCIS or Invasive Breast Cancer.
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 - Group A - VD 3 Weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 3 weeks.
Drug: Vitamin D3
Weekly oral dose of Vitamin D3 per protocol.
Other Names:
  • Toxiferol
  • Cholecalciferol

Active Comparator: Phase 1 - Group B - VD 4 Weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 4 weeks
Drug: Vitamin D3
Weekly oral dose of Vitamin D3 per protocol.
Other Names:
  • Toxiferol
  • Cholecalciferol

Active Comparator: Phase 1 - Group C - VD 5 Weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 5 weeks.
Drug: Vitamin D3
Weekly oral dose of Vitamin D3 per protocol.
Other Names:
  • Toxiferol
  • Cholecalciferol

Experimental: Phase 2 - VD
Weekly oral dose of 50,000 IU Vitamin D3 (VD) therapy for the duration selected from the phase I part of the study.
Drug: Vitamin D3
Weekly oral dose of Vitamin D3 per protocol.
Other Names:
  • Toxiferol
  • Cholecalciferol




Primary Outcome Measures :
  1. Phase 1 - Rate of Treatment-Related Toxicity in Subjects [ Time Frame: From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months ]
    Rate of treatment-related adverse events and other toxicities in subjects.

  2. Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1. [ Time Frame: Up to 7 Weeks ]

    Rate of subjects achieving a "favorable treatment response" to protocol therapy given within the optimal duration determined in Phase 1. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured.

    The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows:

    • 0 (Negative) if <1%
    • +1 (Weak) if >1-10%
    • +2 (Moderate) if >10-50%
    • +3 (Strong) if >50%

    A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".



Secondary Outcome Measures :
  1. Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy [ Time Frame: Up to 7 Weeks ]

    The determination of the optimal duration of once-weekly protocol therapy, 3, 4 or 5 weeks, as preoperative treatment to achieve a "favorable" treatment response in subjects with the study disease. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured.

    The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows:

    • 0 (Negative) if <1%
    • +1 (Weak) if >1-10%
    • +2 (Moderate) if >10-50%
    • +3 (Strong) if >50%

    A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".


  2. Phase 2 - Rate of Treatment-Related Toxicity in Subjects [ Time Frame: From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months ]
    Rate of treatment-related adverse events and other toxicities in subjects.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically confirmed invasive breast carcinoma (IBC) or high grade (DIN3) Ductal Carcinoma in-situ (DCIS) and be scheduled for primary surgery.
  2. Patients must be recommended/scheduled for primary surgery.
  3. Female patients 18 years of age or older.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  5. Patients must have normal organ function as defined below:

    • Aspartate aminotransferase (AST/SGOT) < 4 times institutional upper limit of normal.
    • Alanine transaminase (ALT/SGPT) < 4 times institutional upper limit of normal.
    • Serum Bilirubin < 1.5 mg/dl.
    • Serum Alkaline Phosphatase < 4 times institutional upper limit.
    • Creatinine within normal institutional limits OR; Creatinine clearance >/= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
    • Albumin within normal institutional limits
  6. Women of childbearing potential (WoCBP) must have a negative (serum or urine) pregnancy test and agree to use barrier contraception while on treatment and for 30-days thereafter.
  7. Ability to understand and the willingness to sign a written informed consent document by patient or their legal representatives.

Exclusion Criteria:

  1. Previous history of breast cancer diagnosis or treatment.
  2. Synchronous bilateral breast cancer.
  3. Metastatic breast cancer
  4. Patients recommended for neoadjuvant systemic therapy.
  5. Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 4 weeks preceding the start of study treatment.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
  7. Concurrent other malignancy
  8. Uncontrolled hypertension
  9. Chronic cholestatic or alcoholic liver disease
  10. Chronic pancreatitis
  11. Kidney impairment or renal stones
  12. History of parathyroidectomy
  13. Hypercalcemia, defined as serum level >11 mg/dl.
  14. Abnormal laboratory data for: AST (SGOT), ALT (SGPT), Serum Bilirubin, Alkaline phosphatase, Creatinine and/or Creatinine clearance, and Albumin.
  15. Patients receiving medications that are incompatible with VD.
  16. Prior or known allergic reaction(s) to Vitamin D or other forms of Vitamin D.
  17. Female patients who are pregnant or breast feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02856503


Sponsors and Collaborators
Eli Avisar
Investigators
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Principal Investigator: Eli Avisar, MD University of Miami

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Responsible Party: Eli Avisar, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT02856503     History of Changes
Other Study ID Numbers: 20150288
First Posted: August 5, 2016    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Avisar, University of Miami:
DCIS
IBC
Breast Cancer
Invasive Breast Carcinoma
High Grade Ductal Carcinoma in-situ
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Carcinoma In Situ
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents