Phase II Randomized Study of Neoadjuvant Metformin Plus Letrozole vs Placebo Plus Letrozole for ER-positive Postmenopausal Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 1
- 主要终点
- Clinical response rate
研究概览
简要总结
Preoperative letrozole versus letrozole with metformin in postmenopausal Estrogen receptor positive breast cancer patients
Phase II multicenter 1:1 randomized clinical trial Total 208 patients
Primary endpoint Clinical response rate
Secondary endpoint Pathologic complete response rate Breast conserving surgery rate Percent mammographic density change Ki67(%) change after 4week medication of 2nd core needle biopsy Toxicity profile of neoadjuvant letrozole, metformin
详细描述
To identify the anti-tumor effect of metformin with preoperatively given letrozole in postmenopausal estrogen receptor positive breast cancer patients
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Estrogen receptor positive breast cancer
- •Clinically measurable tumor size(stage II/III)
- •No evidence of distant metastasis
- •Postmenopause women 'Age≥60yr' OR 'previous bilateral oophorectomy' OR 'FSH>30 with no bleeding history within 1yr'
- •Adequate hepatorenal, bone marrow function 'serum Cr<1.4mg/dL' AND 'Bilirubin< upper limit of normal x 1.5 AND 'AST/ALT < upper limit of normal x 1.8 AND 'ALP < upper limit of normal x 1.8 AND 'Hemoglobin >10 g/dL' AND 'ANC >1,500/mm3' AND 'Platelet >100,000/mm3'
- •Spontaneous signed into the written informed consent
排除标准
- •Who does not meet the above inclusion criteria
- •History of other carcinoma
- •Uncontrolled infection
- •History of psychiatric, epileptic disease
- •Male breast cancer
- •Diabetes 'HbA1c≥6.5' OR 'FBS≥126mg/dL'
- •Hypersensitivity or intolerance to metformin
- •Risk of metformin associated lactic acidosis 'Congestive heart disease of NYHA Class llll/IV' OR 'History of other acidosis' OR 'Alcohol intake more than either 3 bottles beer OR 1 bottle Soju'
- •During medication of metformin, sulfonylureas, thiazolidinediones, insulin
- •Diffuse microcalcification in mammogram
- •Multiple OR bilateral OR inflammatory breast cancer
- •Chemotherapy or endocrine therapy within 2yr due to history of breast cancer
研究组 & 干预措施
Arm1_ Metformin
Letrozole with concurrent metformin
干预措施: Metformin (Drug)
Arm 2_ Letrole alone
Letrozole with placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Clinical response rate
时间窗: 24week(after completing medication, preoperatively)
Comparing with RECIST 1.1 From baseline to 24week(after completing medication, preoperatively)
次要结局
- Toxicity profile of letrozole and metformin(throughout the study)
- Breast conservation rate(Baseline-postoperation(within 26weeks after starting medication))
- Breast density change(Baseline-24week(after completing medication, preoperatively))
- Pathologic complete response rate(Postoperation(within 26weeks after starting medication))
- Changes of Ki67(%)(Baseline-4week(second core needle biopsy))