Phase II Study of Acolbifene in Pre-Menopausal Women at High Risk for Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in the Percentage of Breast Epithelial Cells Expressing Ki-67, From Baseline to 6 Months
研究概览
简要总结
This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back.
详细描述
PRIMARY OBJECTIVES:
I. To determine the effect of six months of acolbifene 20 mg/day on Ki-67 in high risk premenopausal women with baseline hyperplasia +/- atypia and Ki-67 positivity of >= 2%..
SECONDARY OBJECTIVES:
I. To determine the effect of six months of acolbifene 20 mg/day on mammographic breast density in high risk premenopausal women.
II. To determine the effect of six months of acolbifene 20 mg/day on serum levels of follicular phase bioavailable estradiol, and luteal phase progesterone, testosterone, and fasting IGF-1/IGFBP-3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Gail risk >= 1.7% and/or relative risk >= 3 times that for 5-year age group
- •Premenopausal
- •More than 6 months since initiating or discontinuing oral contraceptives
- •At increased risk for breast cancer, as indicated by >= 1 of the following risk factors:
- •BRCA1/2 mutation characterized as deleterious or of uncertain significance
- •Prior atypical ductal hyperplasia, ductal carcinoma in situ, or lobular carcinoma in situ
- •Prior random periareolar fine needle aspiration (RPFNA) showing atypical hyperplasia
- •Family history consistent with hereditary breast cancer, as indicated by 1 of the following criteria:
- •>= 4 relatives with breast cancer
- •>= 2 relatives diagnosed with breast cancer at ≤ 50 years of age
- •Breast and ovarian cancer diagnosed in same relative
- •No suspicion for breast cancer on baseline mammogram performed between days 1-10 of menstrual cycle within 3 months prior to screening baseline RPFNA
- •Exhibits hyperplasia with or without atypia (Masood score >= 14) with >= 500 cells AND Ki-67 positivity >= 2% by RPFNA performed within 6 months prior to initiation of study drug
- •Estimated visual mammographic breast density category >= 5% on mammogram performed within 6 months prior to initiation of study drug
- •Has regular menstrual cycles (between 21 and 35 days) unless using extended regimen oral contraceptives or a contraceptive device (e.g., Mirena IUD) Values for metabolic profile and blood count within normal limits
- •Absolute granulocyte count > 1,000/mm^3
- •Platelets > 100,000/mm^3
- •Hemoglobin > 10 g/dL
- •Bilirubin < 2.0 mg/dL
- •AST < 2 times upper limit of normal (ULN)
- •Albumin > 3.0 g/dL
- •Creatinine < 1.5 mg/dL
- •Alkaline phosphatase < 2 times ULN
- •Concurrent hormonal contraceptives allowed provided patient remains on the same hormonal regimen from 3 months prior to baseline aspiration until the completion of study treatment
- •Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- •Willing to ingest recommended dose of calcium and vitamin D for premenopausal bone health (1,200 mg calcium and 800 IU vitamin D daily)
- •Negative pregnancy test prior to receiving study agent
- •Exclusion Criteria
- •pregnant or nursing
- •nursing within the past 6 months
- •Known osteoporosis or severe osteopenia (T-score -2 or worse by DEXA)
- •History of symptomatic endometriosis with pelvic pain, poorly controlled migraines, or hot flashes
- •History of deep venous thrombosis
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to the study agent
- •Other condition or concurrent illness that, in the opinion of the investigator, would make the patient a poor candidate for RPFNA
- •Less than 1 year since prior use of aromatase inhibitors (e.g., anastrozole, exemestane, or letrozole) or selective estrogen receptor modulators (e.g., tamoxifen citrate, raloxifene, or arzoxifene hydrochloride)
- •Other concurrent chemopreventive agents
- •Concurrent anticoagulants
- •Other concurrent investigational agents
- •Bilateral breast implants
排除标准
- 未提供
研究组 & 干预措施
Prevention (acolbifene hydrochloride)
Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.
干预措施: acolbifene hydrochloride (Drug)
结局指标
主要结局
Change in the Percentage of Breast Epithelial Cells Expressing Ki-67, From Baseline to 6 Months
时间窗: Baseline to 6 months
Change in proliferation as measured by Ki-67 immunocytochemical expression in breast epithelial cells obtained by random periareolar fine needle aspiration at baseline and at 6 months.
次要结局
- Change in Mammographic Breast Density(Baseline to 6 months)
- Change in Serum Concentration of Bioavailable Estradiol(Baseline to 6 months)
- Change in Serum Concentration of Testosterone(Baseline to 6 months)
- Change in Serum Estradiol Concentration(Baseline to 6 months)
- Reports of Hot Flashes as Assessed by the Loprinzi Hot Flash Scoring System(Baseline to up to 2 weeks post-treatment)
- Reports of Muscle/Joint Complaints as Assessed by the Validated HAQ II Questionnaire(Baseline to up to 2 weeks post-treatment)
研究者
Carol Fabian, MD
Professor
University of Kansas Medical Center