Sulforaphane: A Dietary Histone Deacetylase (HDAC) Inhibitor in Ductal Carcinoma in Situ (DCIS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy
研究概览
简要总结
RATIONALE: Broccoli sprout extract supplements may slow the growth of tumor cells or abnormal cells and may be an effective treatment for ductal carcinoma in situ and/or atypical ductal hyperplasia.
PURPOSE: This randomized phase II trial is studying how well broccoli sprout extract works in treating women with a diagnosis of breast cancer, ductal carcinoma in situ and/or atypical ductal hyperplasia.
详细描述
OBJECTIVES:
- To determine the correlation between supplemental sulforaphane (broccoli sprout extract) dose and concentrations of sulforaphane and its metabolites in blood and urine samples from women positive for cancer, ductal carcinoma in situ and/or atypical ductal hyperplasia.
- To determine the effect of this supplement on biomarkers of prognosis in these patients.
- To determine the effect of this supplement on HDAC inhibition in peripheral blood cell and normal and cancerous breast tissue samples from these patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Sulforaphane Supplement: Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
- Placebo: Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
Blood and urine samples are collected at baseline and after completion of study treatment for laboratory biomarker studies. Patients scheduled to undergo surgery (mastectomy or lumpectomy) also undergo breast tissue sample collection at baseline and at the time of surgery. Samples are analyzed for sulforaphane metabolism (isothiocyanate levels), HDAC activity (acetylated histone expression), cell proliferation (Ki-67 index by IHC), and apoptosis (TUNEL assay).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnostic mammogram
- •English speaking
排除标准
- •Pregnancy (as determined by urine human chorionic gonadotropin (hCG) test)
- •No biopsy referral after diagnostic mammogram
- •Patient reported breast feeding
- •Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
- •History of or active liver disease or baseline total bilirubin greater than institutional upper limit of normal
- •Patient reported allergy or sensitivity to cruciferous vegetables
- •Use of oral antibiotics within three months prior to randomization
- •Oral steroid therapy at enrollment
- •Current therapy with valproate acid or SAHA
- •Current use of nutrient supplements or herbal remedies containing sulforaphane and unwillingness or inability to quit 72 hours prior to randomization and for the duration of the trial
- •Radiation for currently-diagnosed disease prior to or during study supplementation
- •Chemotherapy for currently-diagnosed disease prior to or during study supplementation
研究组 & 干预措施
Placebo
Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
干预措施: placebo (Other)
Sulforaphane Supplement
Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
干预措施: broccoli sprout extract (Dietary Supplement)
结局指标
主要结局
Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy
时间窗: Baseline and end of study (up to 8 weeks)
Ki-67 was measured through immunohistochemistry method. A modified H-score was recorded, which involved semi-quantitative assessment of both staining intensity (graded as 1-3 with 1 representing weak staining, 2 moderate staining, and 3 strong staining) and percentage of positive cells. The range of the H-score was 0-300. The maximum score indicates the strongest expression, the minimum score indicates no expression of positive tumor area.
Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy
时间窗: Baseline and End of Study (up to 8 weeks)
PBMC HDAC activity was evaluated using the positive control, sodium butyrate.HDAC activity is expressed relative to PBMC protein content and negative control.
Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy
时间窗: Baseline and end of study (up to 8 weeks)
Isothiocyante including sulforaphane in micromolar (µM) concentration was measured following standard chemical measurement procedures and divided by the creatinine values in millimolar (mM) concentration.
次要结局
- Treatment Compliance(Baseline and end of study (up to 8 weeks))
研究者
Jackie Shannon
Principal Investigator
OHSU Knight Cancer Institute