Endometrial Cancer Biomarker Changes Following Exposure to Metformin
- Registration Number
- NCT02042495
- Lead Sponsor
- Jewish General Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Metformin 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.
- Primary Outcome Measures
Name Time Method Change in phosphorylated-S6 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.
- Secondary Outcome Measures
Name Time Method 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 Additional biomarker tested:
* phosphor-IRS1Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt 4-6 weeks Additional biomarker tested:
* phospho-AktAssess each patients insulin resistive state using the HOMA (homeostatic model assessment) index 4-6 weeks Assess the effect of metformin on pre-treatment and post-treatment biomarkers in serum to determine the HOMA index
* fasting IGF-I
* fasting insulin
* fasting IGFBP-1
* fasting glucose levelsEffects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay 4-6 weeks Additional biomarker tested:
* TUNEL assay for apoptosis levelEffects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK 4-6 weeks Additional biomarker tested:
* phosphorylated-AMPKEffects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R 4-6 weeks Additional biomarker tested:
* phosphorylated-IGF-1REffects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67 4-6 weeks Additional biomarker tested:
* Ki-67Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR 4-6 weeks Additional biomarker tested:
* phosphor-mTOREffects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC) 4-6 weeks Additional biomarker tested:
* pACC
Trial Locations
- Locations (1)
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada