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Endometrial Cancer Biomarker Changes Following Exposure to Metformin

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ClinicalTrials.gov Identifier: NCT02042495
Recruitment Status : Withdrawn (Did not obtain Health Canda approval for drug use in reasonable time and moved onward to new trial)
First Posted : January 23, 2014
Last Update Posted : August 30, 2016
Sponsor:
Information provided by (Responsible Party):
Shannon Salvador, Jewish General Hospital

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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Metformin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Trial to Evaluate Endometrial Cancer Biomarker Changes Following Exposure to the Insulin Sensitizer Metformin
Study Start Date : August 2016
Estimated Primary Completion Date : December 2017

Resource links provided by the National Library of Medicine


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 Name: glucophage




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02042495


Locations
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Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T1E2
Sponsors and Collaborators
Jewish General Hospital

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Responsible Party: Shannon Salvador, MD, MSc, FRCSC, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT02042495     History of Changes
Other Study ID Numbers: JGH-140111
First Posted: January 23, 2014    Key Record Dates
Last Update Posted: August 30, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Metformin
Hypoglycemic Agents
Uterine Diseases
Genital Diseases, Female
Physiological Effects of Drugs