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

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02856503
• Other study ID #: 20150288
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: January 2019
• Est. completion date: January 2024

Study information

• Verified date: January 2019
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2024
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Intraductal, Noninfiltrating
• Ductal Carcinoma In-situ
• Invasive Breast Carcinoma

Intervention

Drug:
• Vitamin D3
Weekly oral dose of Vitamin D3 per protocol.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eli Avisar

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy	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".	Up to 7 Weeks
Secondary	Phase 2 - 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