Breast Cancer Prevention Using Synergistic Prostaglandin Inhibitors (The Vitamin D/Celecoxib Study)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- PG synthesis and metabolism
研究概览
简要总结
This is a biomarker study with the goal of measuring changes in proteins and gene methylation. This study is not intended for use in diagnosing, mitigating, treating, curing, or preventing disease.
The purpose of this study is to determine if Vitamin D (cholecalciferol) alone and in combination with celecoxib (Celebrex, a non-steroidal anti-inflammatory drug, or NSAID), to decrease breast cancer risk by their effect on certain biological indicators (biomarkers) of breast cancer risk (called PGE2, COX-2, and 15-PGDH) and cell changes in the breast.
详细描述
This is a biomarker study with the goal of measuring changes in protein and RNA expression. This study is not intended for use in diagnosing, mitigating, treating, curing, or preventing disease.
66 women at high risk for breast cancer (gail risk >/= 1.66% for 5 year risk, or personal or family history)will be recruited and enrolled. 22 women will be randomized into each arm, with anticipation of 2 women in each group will not be evaluable, leaving 20 in each group for evaluation.
A combination of vitamin D and celecoxib act synergistically to decrease breast cancer risk by decreasing cell proliferation in the mammary epithelium through their action on prostaglandin synthesis and metabolism.
Specific Aims:
In women at increased breast cancer risk, determine the effect of vitamin D, with or without celecoxib, on
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women 18 years of age or older
- •Increased risk for breast cancer (demonstrated by strong family history [one 1st degree or two 2nd degree relatives], history of DCIS, IBC, or precancerous changes in breasts). OR Gail Model risk of developing IBC in a 5-year period of >1.66%
- •Women with a history of breast cancer, must be free of disease and finished with treatment
- •ECOG Performance Status score 0-1
- •Premenopausal women must not be pregnant.
排除标准
- •History of bilateral mastectomy, or bilateral breast irradiation
- •Significant medical or psychiatric problems making the participant a poor candidate
- •Evidence of excess use of narcotics or drug dependency
- •Have been pregnant and lactating in the past 2 years
- •Significant history of peptic ulcer disease or upper gastrointestinal bleeding
- •History of severe congestive heart failure that requires hospitalization or intervention
- •History of asthma requiring medication for treatment
- •Allergy to sulfonamides or NSAID medications
- •History of myocardial infarction or stroke
- •Currently on Coumadin
- •Currently on Tamoxifen (nolvadex),Evista (raloxifene), Femara (letrozole), Arimidex (anastrozole), or Aromasin (exemestane)
- •Undergone prior subaeolar breast surgery
研究组 & 干预措施
Placebo & cholecalciferol 400 IU
In this arm, the placebo is in place of celecoxib and the current RDA for cholecalciferol is used the control of the cholecalciferol higher dose.
干预措施: Placebo (Drug)
Placebo & cholecalciferol 400 IU
In this arm, the placebo is in place of celecoxib and the current RDA for cholecalciferol is used the control of the cholecalciferol higher dose.
干预措施: Cholecalciferol (Drug)
Placebo & cholecalciferol 2,000 IU
干预措施: Placebo (Drug)
Placebo & cholecalciferol 2,000 IU
干预措施: Cholecalciferol (Drug)
celecoxib 400 mg & cholecalciferol 2,000 IU
干预措施: Celecoxib (Drug)
celecoxib 400 mg & cholecalciferol 2,000 IU
干预措施: Cholecalciferol (Drug)
结局指标
主要结局
PG synthesis and metabolism
时间窗: approximately 30 days
This will be measured from both baseline and completion samples. 1. PG synthesis and metabolism, through the measurement of 15-PGDH, COX-2, and PGE2 in the breast Rationale: 1,25(OH)2D, the active form of vitamin D, has been shown in vitro to decrease PGE2 both by interfering with its production and by increasing its breakdown, leading to lower cell proliferation. Celecoxib potentiated the antiproliferative effect, allowing a much lower dose of each agent when used in combination than in isolation.
次要结局
- Proliferative activity in the breast, as measured by MD cell morphology(approximately 30 days)
- Circulating levels of 25(OH)D, 1,25(OH)2D, and celecoxib(approximately 30 days)
研究者
Edward Sauter
MD, PhD, M.H.A
The University of Texas Health Science Center at Tyler