Endometrial Cancer
Conditions
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.
Interventions
DRUGMetformin
Sponsors
Jewish General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Assess 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 levels |
| Effects 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 level |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK | 4-6 weeks | Additional biomarker tested: * phosphorylated-AMPK |
| Effects 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-1R |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67 | 4-6 weeks | Additional biomarker tested: * Ki-67 |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt | 4-6 weeks | Additional biomarker tested: * phospho-Akt |
| Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR | 4-6 weeks | Additional biomarker tested: * phosphor-mTOR |
| Effects 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 |
| 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-IRS1 |
Countries
Canada
Outcome results
None listed