Brief Title
Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer
Official Title
Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer
Brief 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.
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Change in Ki-67 mean levels between pre-metformin treatment endometrial biopsies and post-metformin treatment hysterectomy specimens
Condition
Endometrial Cancer
Intervention
Metformin
Study Arms / Comparison Groups
Arm 1
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
28
Start Date
May 2011
Completion Date
February 2013
Primary Completion Date
February 2013
Eligibility Criteria
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
Gender
Female
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Victoria Bae-Jump, M.D. PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01911247
Organization ID
LCCC1102
Secondary IDs
1K23CA143154-01A1
Responsible Party
Sponsor
Study Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Institutes of Health (NIH)
Study Sponsor
Victoria Bae-Jump, M.D. PhD, Principal Investigator, UNC Lineberger Comprehensive Cancer Center
Verification Date
July 2013