Clinical trial NCT02856503: Effect of High Dose Vitamin D on Cancer Biomarkers and Breast Cancer Tumors
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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Invasive Breast Carcinoma
Ductal Carcinoma In-situ
Keywords: DCIS
IBC
Breast Cancer
Invasive Breast Carcinoma
High Grade Ductal Carcinoma in-situ
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2016-08-05
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Phase 1 - Rate of Treatment-Related Toxicity in Subjects
timeFrame: From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months
measure: Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1.
timeFrame: Up to 7 Weeks
Secondary outcomes:
measure: Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy
timeFrame: Up to 7 Weeks
measure: Phase 2 - Rate of Treatment-Related Toxicity in Subjects
timeFrame: From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months
Other outcomes:
Locations:
Study officials:
affiliation: University of Miami
name: Eli Avisar, MD
role: PRINCIPAL_INVESTIGATOR
References: