Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT01911247|
Recruitment Status : Completed
First Posted : July 30, 2013
Last Update Posted : July 30, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Endometrial Cancer||Drug: Metformin||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer|
|Study Start Date :||May 2011|
|Actual Primary Completion Date :||February 2013|
|Actual Study Completion Date :||February 2013|
|Experimental: Arm 1||
Metformin 850 mg once daily
- 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.
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): NCT01911247
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||Victoria Bae-Jump, M.D. PhD||UNC Lineberger Comprehensive Cancer Center|