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

NCT02856503 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 20150288
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Breast Cancer; Invasive Breast Carcinoma; Ductal Carcinoma In-situ

Keywords

DCIS; IBC; Breast Cancer; Invasive Breast Carcinoma; High Grade Ductal Carcinoma in-situ

Outcome Measures

Primary Outcomes (2)

• Phase 1 - Rate of Treatment-Related Toxicity in Subjects

  Rate of treatment-related adverse events and other toxicities in subjects.

  From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months

• Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1.

  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".

  Up to 7 Weeks

Secondary Outcomes (2)

• Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy

  Up to 7 Weeks

• Phase 2 - Rate of Treatment-Related Toxicity in Subjects

  From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months

Study Arms (4)

Phase 1 - Group A - VD 3 Weeks

EXPERIMENTAL

Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 3 weeks.

Drug: Vitamin D3

Phase 1 - Group B - VD 4 Weeks

ACTIVE COMPARATOR

Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 4 weeks

Drug: Vitamin D3

Phase 1 - Group C - VD 5 Weeks

ACTIVE COMPARATOR

Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 5 weeks.

Drug: Vitamin D3

Phase 2 - VD

EXPERIMENTAL

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

Interventions

Vitamin D3 DRUG

Weekly oral dose of Vitamin D3 per protocol.

Also known as: Toxiferol, Cholecalciferol

Phase 1 - Group A - VD 3 Weeks; Phase 1 - Group B - VD 4 Weeks; Phase 1 - Group C - VD 5 Weeks; Phase 2 - VD

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed invasive breast carcinoma (IBC) or high grade (DIN3) Ductal Carcinoma in-situ (DCIS) and be scheduled for primary surgery.
• Patients must be recommended/scheduled for primary surgery.
• Female patients 18 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• 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
• 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.
• Ability to understand and the willingness to sign a written informed consent document by patient or their legal representatives.

You may not qualify if:

• Previous history of breast cancer diagnosis or treatment.
• Synchronous bilateral breast cancer.
• Metastatic breast cancer
• Patients recommended for neoadjuvant systemic therapy.
• 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.
• 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.
• Concurrent other malignancy
• Uncontrolled hypertension
• Chronic cholestatic or alcoholic liver disease
• Chronic pancreatitis
• Kidney impairment or renal stones
• History of parathyroidectomy
• Hypercalcemia, defined as serum level \>11 mg/dl.
• Abnormal laboratory data for: AST (SGOT), ALT (SGPT), Serum Bilirubin, Alkaline phosphatase, Creatinine and/or Creatinine clearance, and Albumin.
• Patients receiving medications that are incompatible with VD.

Sponsors & Collaborators

• Eli Avisar, MD: lead

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Eli Avisar, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: August 5, 2016
• Study Start: January 13, 2019
• Primary Completion: January 31, 2023
• Study Completion: April 15, 2024
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share