Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer

Endometrial Cancer Clinical Trial

Official title:

Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01911247
• Other study ID #: LCCC1102
• Secondary ID: 1K23CA143154-01A
• Status: Completed
• Phase: Phase 0
• First received: July 23, 2013
• Last updated: July 25, 2013
• Start date: May 2011
• Est. completion date: February 2013

Study information

• Verified date: July 2013
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The overall goal of this proposal is to investigate the potential benefit of metformin as a novel therapy for the treatment of endometrial cancer. Investigators will evaluate the effect of short-term metformin treatment on the endometrium of obese women with endometrial cancer by comparing each patient's endometrial biopsy before treatment with metformin to their post-treatment hysterectomy specimen.

Participants: Obese women who are to undergo surgical staging for endometrial cancer will also receive short-term treatment (1-4 weeks) with metformin that will continue until the day prior to surgical staging.

The effect of metformin on proliferation, apoptosis and downstream signaling pathways will be compared between pre-treatment endometrial biopsies and post-treatment hysterectomy specimens. Tissue microarrays will be constructed and immunohistochemstry performed to evaluate proliferation, apoptosis and changes in critical signaling pathways mediated by metformin, and these findings will be correlated with our in vitro preclinical studies. Fresh tissue will also be obtained, and Western immunoblotting will be used to assess expression of the phosphorylated forms of the downstream targets of metformin. The hypothesis is that treatment with metformin will result in a decrease in proliferative markers and an increase in markers of apoptosis in the endometrial cancer tumors. AMPK phosphorylation and inhibition of critical downstream targets of the mTOR pathway will be seen in the post-treatment hysterectomy specimens. Metabolomic profiling will also be performed of tumors and associated biofluids (i.e. serum and urine) before and after treatment with metformin to identify potential biomarkers of response to this therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Be between the ages of 18-75 years old

• Have a confirmed diagnosis of type I endometrial cancer (endometrioid) based on pre-operative endometrial biopsy or dilation and curettage (D&C)

• Be obese (BMI greater than or equal to 30) with or without diabetes

• Have no contraindications to short-term metformin therapy

• Have a serum creatinine greater 1.0 mg/dL

• Have normal serum transaminase values (AST and ALT)

• Need to be able to undergo metformin treatment for a minimum of 1 weeks but no more than a maximum of 4 weeks prior to surgical staging

Exclusion Criteria:

• Are currently taking metformin or have taken metformin in the past 6 months or have a history of an allergic reaction or intolerance at any time to metformin

• Have a history of liver or renal dysfunction

• Have a history of alcoholism

• Have a history of vitamin B12 deficiency

• Are pregnant

• Are currently taking insulin

• Are currently taking any hormonal therapy or have been on hormonal therapy in the past 4 weeks

• Are taking a drug that may significantly interact or influence the metabolism of metformin

• In the opinion of the investigator, the patient is felt not to be appropriate for the study

Study Design

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• Metformin
Metformin 850 mg once daily

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Ki-67 mean levels between pre-metformin treatment endometrial biopsies and post-metformin treatment hysterectomy specimens	The primary null hypothesis of interest, that there is no difference between the pre- and post-treatment Ki-67 mean levels will be evaluated using a paired t-test (two-sided, a<0.05 level). Paired t-tests will also be used to compare pre- and post-treatment measures of secondary endpoints. General linear models will be used to explore the relationship between pre-treatment characteristics (e.g., ER, PR, tumor grade) and change in Ki-67, Ki-max and Ki-min.	4 weeks	No