Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 3
- 主要终点
- Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer
研究概览
简要总结
This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of letrozole may keep cancer from forming in healthy postmenopausal women at high risk for breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. Compare the effect of lower and intermittent doses of letrozole to standard letrozole therapy on estrogen suppression in postmenopausal women at high risk for developing breast cancer.
SECONDARY OBJECTIVES:
I. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on signs and symptoms of estrogen deficiency, including menopausal symptoms, serum lipid profile, and serum marker of bone turnover.
II. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on nuclear chromatin abnormality of breast epithelial cells collected by random periareolar fine needle aspiration (RPFNA).
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
- 35 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy postmenopausal women at "high risk" for breast cancer will be eligible for the study; definition of menopause will be:
- •Amenorrhea for at least 12 months, or
- •History of hysterectomy and bilateral salpingo-oophorectomy, or
- •At least 55 years of age with prior hysterectomy with or without oophorectomy, or
- •Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range
- •"High risk" for breast cancer will be defined as:
- •Prior histologically confirmed lobular carcinoma in situ (LCIS) treated by local excision only, or
- •At least 1.66% probability of invasive breast cancer within 5 years using the Breast Cancer Risk Assessment Tool
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Karnofsky 80% or above
- •Leukocytes >= 3,000/uL
- •Absolute neutrophil count >= 1,500/uL
- •Platelets >= 100,000/uL
- •Total bilirubin =< 2.0 mg/dL
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 X institutional ULN
- •Creatinine =< 1 X institutional ULN
- •Recent mammogram negative for breast cancer, Breast Imaging-Reporting and Data System (BIRADS) score < 3 (within the last 12 months)
- •Ability to understand and the willingness to sign a written informed consent document; only potential participants with the ability to understand and the willingness to sign a written document will be presented with an informed consenting document
排除标准
- •Women diagnosed with osteoporosis (previously or on screening dual-energy X-ray absorptiometry [DEXA] for this study) and not on a stable dose of long or short-acting bisphosphonates therapy for at least 3 months will be excluded from the study; women diagnosed with osteoporosis and on raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia will be allowed to participate in this study
- •Have had invasive cancer within the past five years except non-melanoma skin cancer
- •Evidence of suspicious of malignant disease on bilateral mammogram within the past year unless ruled out by further evaluation
- •History of prior invasive breast cancer or intraductal carcinoma in situ, or history of prior radiation therapy to the chest or breast
- •Participants may not be receiving any other investigational agents; participants may not be concurrently enrolled in another breast cancer prevention intervention trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to letrozole
- •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 study requirements
- •Within 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens
- •Within 3 months since prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators
- •Within 3 months since regular use (more than 2 times a week) of prior estrogenic supplements or herbal remedies
- •History of bleeding or clotting disorder; current or recent (within 3 months) use of Coumadin, Plavix or other systemic anticoagulant other than aspirin is not permitted if subject chooses to participate in the optional RPFNA procedure; if a subject chooses not to participate in the RPFNA procedure, prior or current treatment with systemic anticoagulants is permitted
研究组 & 干预措施
Arm I (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO thrice weekly for 6 months.
干预措施: letrozole (Drug)
Arm I (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO thrice weekly for 6 months.
干预措施: quality-of-life assessment (Other)
Arm I (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO thrice weekly for 6 months.
干预措施: laboratory biomarker analysis (Other)
Arm II (1.0 mg letrozole)
Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.
干预措施: letrozole (Drug)
Arm II (1.0 mg letrozole)
Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.
干预措施: quality-of-life assessment (Other)
Arm II (1.0 mg letrozole)
Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.
干预措施: laboratory biomarker analysis (Other)
Arm III (0.25 mg letrozole)
Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.
干预措施: letrozole (Drug)
Arm III (0.25 mg letrozole)
Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.
干预措施: quality-of-life assessment (Other)
Arm III (0.25 mg letrozole)
Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.
干预措施: laboratory biomarker analysis (Other)
Arm IV (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO once daily for 6 months.
干预措施: letrozole (Drug)
Arm IV (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO once daily for 6 months.
干预措施: quality-of-life assessment (Other)
Arm IV (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO once daily for 6 months.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer
时间窗: Baseline to week 30
Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.
次要结局
- Menopausal symptoms as assessed by quality of life measures, as assessed by Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Menopause Specific Quality of Life Questionnaire (MENQOL)(Up to week 30)
- Nuclear chromatin abnormality as assessed by karyometry(Up to week 30)
- Change in serum estrone levels(Baseline to week 30)
- Change in serum testosterone levels(Baseline to week 30)