A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Change in phosphorylated-S6
研究概览
简要总结
The investigators will explore the chemopreventive role of metformin. The purpose of this study is to determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue. This is a phase IIa study of metformin to be used to the pre-operative period of women diagnosed with endometrial cancer by comparing their endometrial biopsy specimens taken at their initial visit and after 4-6 weeks of treatment of metformin on the day of their surgical staging.
详细描述
Aim 1 To determine whether, among patients with endometrial cancer, treatment with the currently approved insulin sensitizing drug metformin increases or decreases pathway activation distal to the insulin receptor in endometrial cancer tissue.
Aim II To compare specified biomarkers in each endometrial cancer patient before and after receiving metformin. Our goal is to compare the following biomarkers in each patient before and after metformin administration: Ki-67, TUNEL assay for apoptosis level, phosphor-AMPK, phosphor-IGF-1R, phosphor-IRS1, phospho-Akt, phospho-S6, phosphor-mTOR, pACC.
All patients diagnosed with endometrial cancer presenting to the Jewish General Hospital for surgical treatment will be invited to participate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Have a confirmed diagnosis of endometrial cancer based on an endometrial sampling though biopsy or dilatation and curettage
- •Must be able to undergo appropriate surgical staging for endometrial cancer
- •Must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to government and institutional guidelines
排除标准
- •Patients with a contraindication to receiving metformin treatment
- •Patients with cognitive impairment
- •Renal or hepatic functioning > 125% upper limit of normal
- •Currently on medications for metabolic diseases, such as diabetes mellitus
- •History of lactic acidosis
- •Treatment with medications that may increase metformin levels: cationic drugs, e.g., digoxin, amiloride, procainamide, trimethoprim, vancomycin, triamterene, and morphine
- •History of chronic alcohol abuse
研究组 & 干预措施
Metformin
Metformin 500 mg PO TID from time of entry to study until scheduled surgical staging operation.
In cases of unresolving side effects, the metformin will be dose reduced to metformin 500 mg PO BID with evaluation after 1 week followed by withdrawal from the study if side effects persist.
干预措施: Metformin (Drug)
结局指标
主要结局
Change in phosphorylated-S6
时间窗: 4-6 weeks
Paired-t test will be used to determine the effect of oral metformin on the phosphorylated-S6 in pre-treatment and post-treatment endometrial samples.
次要结局
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt(4-6 weeks)
- Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR(4-6 weeks)
- Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)(4-6 weeks)
研究者
Shannon Salvador
MD, MSc, FRCSC
Jewish General Hospital