Endometrial Cancer Biomarker Changes Following Exposure to Metformin

NCT02042495 | Withdrawn Phase 2

• 1 other identifier: JGH-140111
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing Ki-67

  4-6 weeks

• Assess each patients insulin resistive state using the HOMA (homeostatic model assessment) index

  4-6 weeks

• Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing the TUNEL assay

  4-6 weeks

• Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated AMPK

  4-6 weeks

• Effects of metformin on activation pathways downstream of the insulin receptor in endometrial samples by testing phosphorylated IGF-1R

  4-6 weeks

Study Arms (1)

Metformin

EXPERIMENTAL

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

Interventions

Metformin DRUG

Also known as: glucophage

Metformin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jewish General Hospital: lead

Study Sites (1)

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MSc, FRCSC

Study Record Dates

• First Submitted: January 12, 2014
• First Posted: January 23, 2014
• Study Start: August 1, 2016
• Primary Completion: December 1, 2017
• Last Updated: August 30, 2016

Record last verified: 2016-08

Locations

CA (1)