Clinical trial NCT02042495: Endometrial Cancer Biomarker Changes Following Exposure to Metformin
Official title: A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Endometrial Cancer
Lead sponsor: Jewish General Hospital
Sponsor class: OTHER
First posted: 2014-01-23
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in phosphorylated-S6
timeFrame: 4-6 weeks
Secondary outcomes:
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67
timeFrame: 4-6 weeks
measure: Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR
timeFrame: 4-6 weeks
measure: Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)
timeFrame: 4-6 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
References: