Metformin Hydrochloride vs. Placebo in Overweight or Obese Patients at Elevated Risk for Breast Cancer
A Double Blind Prospective Study of Metformin vs. Placebo in Overweight or Obese Post-menopausal Women at Elevated Risk for Breast Cancer
研究概览
详细说明
PRIMARY OBJECTIVES:
I. To determine the changes in the signal pathway profiling of breast tissue using reverse phase proteomics in tissue biopsy of overweight or obese women at elevated risk for breast cancer treated with metformin (metformin hydrochloride) (850mg orally twice a day) for 12 cycles.
SECONDARY OBJECTIVES:
I. To determine the effect of metformin on breast tissue density of overweight or obese women at elevated risk for breast cancer using qualitative mammographic fat density criteria.
II. To determine the effect of metformin on the insulin axis in serum of overweight or obese women at elevated risk for breast cancer treated with metformin (850mg orally twice a day) for 12 cycles.
III. To determine the toxicities associated with metformin.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 5 years.
研究类型
注册 (实际的)
阶段
- 第一阶段早期
联系人和位置
学习地点
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Indiana
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Indianapolis、Indiana、美国、46202
- Indiana University Melvin and Bren Simon Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Patients must be post-menopausal women; post-menopausal women are defined as: (1) those >= 50 years of age who had not menstruated during the preceding 12 months or who had castrate follicle-stimulating hormone levels (> 40 IU/L), (2) those who had undergone a bilateral oophorectomy
Patients must be at elevated risk for breast cancer based on strong family history or a history of breast biopsy documenting atypical hyperplasia anytime in the past; for this study strong family history is defined as having:
- 1 first-degree (parent, offspring, sibling) relative =< 50 years old when diagnosed with breast cancer, or
- >= 2 first-degree relatives of any age when diagnosed with breast cancer, or
- >= 2 second-degree (aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings) maternal or paternal relatives diagnosed with breast cancer and at least 1 diagnosed at =< 50 years of age
Patients must have a body mass index (BMI) >= 25.0 as calculated by the formula: weight in pounds / height squared x 703 = BMI; a BMI of:
- 18.5-24.9 is considered normal;
- 25.0-29.9 is considered overweight;
- 30.0+ is regarded as obese
- Patients must be willing to complete a bilateral mammogram at baseline with repeat exam after 12 cycles of protocol therapy; patients who have had a mammogram within 1 month prior to registration to protocol therapy will not need to repeat the exam
- Patients must be willing to provide a core tissue biopsy at baseline and with repeat tissue collection after 12 cycles of protocol therapy
- White blood cell (WBC) >= 3.0 x 109/L
- Granulocytes (polymorphs + bands) >= 1.5 x 109/L
- Platelets >= 100 x 109/L
- Hemoglobin >= 110 g/L
- Aspartate aminotransferase (AST) =< 1.8 X upper limit of normal (ULN)
- Alanine aminotransferase (ALT) =< 1.8 X ULN
- Alkaline phosphatase =< 2 X ULN
- Serum creatinine =< 115 umol/L (1.3mg/dL)
- Serum bilirubin =< institution ULN (except for subjects with Gilbert's Disease who are eligible despite elevated serum bilirubin level)
- 12 hour fasting glucose level < 7.0 mmol/L
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 within 28 days of registration
- Life expectancy of >= 5 years
- Subjects must be accessible for treatment, adverse event tracking and follow-up as determined by the treating physician
- Subject consent and authorization for the release of health information must be obtained according to local institutional guidelines
Exclusion Criteria:
- No history of any malignancy except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >= 5 years
- No known diabetes (type 1 or 2) or baseline fasting glucose >= 7.0 mmol/L
- No known hypersensitivity or intolerance to metformin
- No condition associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heart failure defined as New York Heart Association [NYHA] class III or IV functional status, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day)
- No current treatment with metformin, sulfonylureas, thiazolidinediones or insulin for any reason
- No breastfeeding
- No concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, insulin-like growth factor 1 (IGF-1) or their receptors
学习计划
研究是如何设计的?
设计细节
- 主要用途:预防
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Arm I (metformin hydrochloride)
Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter.
Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
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相关研究
给定采购订单
其他名称:
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安慰剂比较:Arm II (placebo)
Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter.
Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
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相关研究
给定采购订单
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Changes in the phosphorylation of proteins after metformin exposure
大体时间:Baseline and 12 months
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Reverse phase proteomic assays (RPPA) will be performed to measure changes in the phosphorylation of proteins after metformin exposure.
Changes in the phosphorylation of proteins after metformin exposure will be calculated and compared using two-sample t-tests.
As a supplemental analysis, analysis of covariance (ANCOVA) will be used to model the 12 month levels adjusted for baseline.
Assumptions for analysis will be checked and non-parametric methods used if needed; however it is expected that the data will be normally distributed on the log scale.
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Baseline and 12 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Changes in ordinal level of breast density
大体时间:Baseline and 12 months
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Changes in ordinal level of breast density will be performed using the breast density criteria previously established by Boyd and colleagues (New England Journal of Medicine 2007).
Each image will be grouped into one of six categories: 0%, <10%, 10-25%, 25-50%, 50-75% and >75%.
Changes will be compared between the two groups using Wilcoxon Rank-Sum tests.
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Baseline and 12 months
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Proportion of patients experiencing adverse events assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
大体时间:Up to 30 days
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Will be tabulated by arm and grade.
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Up to 30 days
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合作者和调查者
调查人员
- 首席研究员:Anna Maria Storniolo, MD、Indiana University Melvin and Bren Simon Cancer Center
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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