Endometrial Cancer Biomarker Changes Following Exposure to Metformin

August 29, 2016 updated by: Shannon Salvador, Jewish General Hospital

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T1E2
        • Jewish General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Metformin
Other Names:
  • glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in phosphorylated-S6
Time Frame: 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.
4-6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67
Time Frame: 4-6 weeks

Additional biomarker tested:

  • Ki-67
4-6 weeks
Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index
Time Frame: 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
4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay
Time Frame: 4-6 weeks

Additional biomarker tested:

  • TUNEL assay for apoptosis level
4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK
Time Frame: 4-6 weeks

Additional biomarker tested:

  • phosphorylated-AMPK
4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R
Time Frame: 4-6 weeks

Additional biomarker tested:

  • phosphorylated-IGF-1R
4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)
Time Frame: 4-6 weeks

Additional biomarker tested:

  • phosphor-IRS1
4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt
Time Frame: 4-6 weeks

Additional biomarker tested:

  • phospho-Akt
4-6 weeks
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR
Time Frame: 4-6 weeks

Additional biomarker tested:

  • phosphor-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)
Time Frame: 4-6 weeks

Additional biomarker tested:

  • pACC
4-6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jewish General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2016

Primary Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

January 12, 2014

First Submitted That Met QC Criteria

January 19, 2014

First Posted (Estimate)

January 23, 2014

Study Record Updates

Last Update Posted (Estimate)

August 30, 2016

Last Update Submitted That Met QC Criteria

August 29, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JGH-140111

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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