Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer
Status:
Completed
Trial end date:
2013-02-01
Target enrollment:
Participant gender:
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.
Phase:
Early Phase 1
Details
Lead Sponsor:
UNC Lineberger Comprehensive Cancer Center
Collaborators:
National Cancer Institute (NCI) National Institutes of Health (NIH)