Phase IIB Randomized Controlled Biomarker Modulation Study of Vitamin D in Premenopausal Women at High Risk for Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 719
- 主要终点
- Change in mammographic density at 12 months compared to baseline
研究概览
简要总结
RATIONALE: Cholecalciferol may prevent breast cancer in premenopausal women.
PURPOSE: This randomized phase II trial is studying how well cholecalciferol works in preventing breast cancer in premenopausal women.
详细描述
OBJECTIVES:
- To assess whether mammographic density is reduced in premenopausal women at high risk of breast cancer taking high-dose vitamin D3 (oral cholecalciferol 20,000 IU weekly) vs placebo for 1 year.
- To assess whether proliferation as measured by Ki-67 staining of breast epithelial cells is reduced in women receiving these treatments.
- To explore the difference in the expression of other biomarkers (including cleaved caspase-3 [apoptosis marker], ER, vitamin D receptor [VDR], and 1α-hydroxylase) in breast tissue obtained from these women.
- To assess whether parathyroid hormone, IGF-1, IGFBP-3, 25(OH)D, and 1,25(OH)D serum levels are altered in these women at baseline and at 6 and 12 months.
- To explore whether a change in mammographic density correlates with polymorphisms in the VDR gene.
- To assess other sources of vitamin D (sunlight exposure, diet) in these women using a validated questionnaire administered at baseline and at 12 and 24 months.
- To collect and bank serum, plasma, and breast tissue from these women before and after a 1-year intervention with vitamin D for future biomarker analysis.
- To assess the toxicity of high-dose cholecalciferol compared to placebo in this setting.
OUTLINE: This is a multicenter study. Participants are stratified according to baseline serum 25(OH)D level (< 20 ng/mL vs 20-32 ng/mL or < 50 nmol/L vs 50-80 nmol/L), baseline mammographic density (11-50% vs > 50%), and designated biopsy site (yes vs no). Participants are randomized to 1 of 2 treatment arms.
- Arm I: Participants receive oral cholecalciferol once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.
- Arm II: Participants receive oral placebo once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.
Blood samples are collected at baseline and periodically thereafter for biomarkers and 25(OH)D level. Participants undergo a mammogram at baseline and at 12 months. Participants may also undergo random core-needle breast biopsy at baseline and at 12 months.
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 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Participants receive oral cholecalciferol once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.
干预措施: cholecalciferol (Dietary Supplement)
Arm II
Participants receive oral placebo once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.
干预措施: placebo (Other)
Arm II
Participants receive oral placebo once weekly and oral vitamin D once daily. Treatment repeats for 12 months in the absence of evidence of cancer or unacceptable toxicity.
干预措施: cholecalciferol (Dietary Supplement)
结局指标
主要结局
Change in mammographic density at 12 months compared to baseline
时间窗: 12 months
次要结局
- Ki-67 as assessed in tissue obtained in breast biopsies at baseline and at 12 months(12 months)