Endometrial Cancer Biomarker Changes Following Exposure to Metformin

Endometrial Cancer Clinical Trial

Official title:

A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02042495
• Other study ID #: JGH-140111
• Status: Withdrawn
• Phase: Phase 2
• First received: January 12, 2014
• Last updated: August 29, 2016
• Start date: August 2016

Study information

• Verified date: August 2016
• Source: Jewish General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• Metformin

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Jewish General Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in phosphorylated-S6	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.	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67	Additional biomarker tested: Ki-67	4-6 weeks	No
Secondary	Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index	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	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay	Additional biomarker tested: TUNEL assay for apoptosis level	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK	Additional biomarker tested: phosphorylated-AMPK	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R	Additional biomarker tested: phosphorylated-IGF-1R	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)	Additional biomarker tested: phosphor-IRS1	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt	Additional biomarker tested: phospho-Akt	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR	Additional biomarker tested: phosphor-mTOR	4-6 weeks	No
Secondary	Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)	Additional biomarker tested: pACC	4-6 weeks	No