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Endometrial Cancer Biomarker Changes Following Exposure to Metformin

Primary Purpose

Endometrial Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Sponsored by
Jewish General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Jewish General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metformin

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67
Additional biomarker tested: Ki-67
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
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
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK
Additional biomarker tested: phosphorylated-AMPK
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
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
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt
Additional biomarker tested: phospho-Akt
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR
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)
Additional biomarker tested: pACC

Full Information

First Posted
January 12, 2014
Last Updated
August 29, 2016
Sponsor
Jewish General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02042495
Brief Title
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

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Did not obtain Health Canda approval for drug use in reasonable time and moved onward to new trial
Study Start Date
August 2016 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jewish General Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
glucophage
Primary Outcome Measure Information:
Title
Change in phosphorylated-S6
Description
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.
Time Frame
4-6 weeks
Secondary Outcome Measure Information:
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67
Description
Additional biomarker tested: Ki-67
Time Frame
4-6 weeks
Title
Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index
Description
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
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay
Description
Additional biomarker tested: TUNEL assay for apoptosis level
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK
Description
Additional biomarker tested: phosphorylated-AMPK
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R
Description
Additional biomarker tested: phosphorylated-IGF-1R
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated insulin-receptor substrate protein 1 (phosphor-IRS1)
Description
Additional biomarker tested: phosphor-IRS1
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated-Akt
Description
Additional biomarker tested: phospho-Akt
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated mTOR
Description
Additional biomarker tested: phosphor-mTOR
Time Frame
4-6 weeks
Title
Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated acetyl-CoA carboxylase (pACC)
Description
Additional biomarker tested: pACC
Time Frame
4-6 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T1E2
Country
Canada

12. IPD Sharing Statement

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Endometrial Cancer Biomarker Changes Following Exposure to Metformin

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