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.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Phase 1 - Rate of Treatment-Related Toxicity in Subjects
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
- •Prior or known allergic reaction(s) to Vitamin D or other forms of Vitamin D.
- •Female patients who are pregnant or breast feeding.
研究组 & 干预措施
Phase 1 - Group B - VD 4 Weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 4 weeks
干预措施: Vitamin D3 (Drug)
Phase 1 - Group C - VD 5 Weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 5 weeks.
干预措施: Vitamin D3 (Drug)
Phase 1 - Group A - VD 3 Weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 3 weeks.
干预措施: Vitamin D3 (Drug)
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.
干预措施: Vitamin D3 (Drug)
结局指标
主要结局
Phase 1 - Rate of Treatment-Related Toxicity in Subjects
时间窗: 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.
Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1.
时间窗: 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".
次要结局
- 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)
研究者
Eli Avisar, MD
Professor
University of Miami