Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer

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.

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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Early Phase 1

Primary location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

metformin

Drug

Metformin 850 mg once daily

Primary outcomes

Change in Ki-67 mean levels between pre-metformin treatment endometrial biopsies and post-metformin treatment hysterectomy specimens

Time frame: 4 weeks

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, α<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.

Sponsors and collaborators

Lead sponsor

UNC Lineberger Comprehensive Cancer Center

Other

Collaborators

National Cancer Institute (NCI)
National Institutes of Health (NIH)

Registry information

Important dates

Study start: 2011
Primary completion: 2013
Study completion: 2013
First posted: Jul 30, 2013
Registry last updated: Jul 30, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed