Brief Title
Evaluation of the Molecular Effects of Metformin on the Endometrium in Patients With Endometrial Cancer
Official Title
Evaluation of the Molecular Effects of Metformin on the Endometrium in Patients With Endometrial Cancer
Brief Summary
The goal of this research study is to learn if metformin can affect endometrial cancer cells
in women who do not have diabetes.
Objectives:
Primary Objectives:
1. To determine the molecular effects of metformin and associated physiologic changes in
insulin/glucose metabolism on the mTOR (mammalian target of rapamycin) signaling pathway in
the endometrium of women with endometrial cancer
Secondary Objectives:
1. To describe the effects of metformin on the histology and proliferation of the
endometrium in women with endometrial cancer.
2. To assess the effect of body mass index on the response to treatment with metformin
3. To assess the effect of insulin resistance on the response to treatment with metformin
4. To determine effects of metformin on the serum, urine and DNA biomarkers of women with
endometrial cancer.
Detailed Description
The Study Drug:
Metformin is designed to treat both diabetes and insulin resistance. Both diabetes and
insulin resistance have been linked to endometrial cancer. Although you do not have a
diagnosis of diabetes, metformin may still have an affect on your cancer cells.
Study Visit (before taking Metformin):
If you are found eligible to take part in this study, you will have a study visit before you
begin taking Metformin. The following tests and procedures will be performed:
- Blood (about 2 tablespoons) and urine will be collected for research to look at
different hormone levels.
- If needed, a fasting glucose level will be obtained.
- If you are found not to be eligible your blood, urine, and tissue for research will be
discarded.
Study Drug Administration:
You will take metformin, by mouth, 1 time each morning, with breakfast, for at least 7 days
and up to 30 days until your scheduled surgery is performed. You will record the dates and
times you take metformin on a study drug calendar provided by the study staff. You will not
take metformin on the day of your surgery.
Study Tests (on the day of your surgery):
You will bring your study drug calendar to the clinic on the day of your surgery. The
following tests and procedures will also be performed:
- Blood (about 2 tablespoons) and urine will be collected for routine tests and to check
different hormone levels.
- During surgery, you will have a second endometrial biopsy for biomarker testing.
Length of Study:
You will be off study after your surgical procedure.
This is an investigational study.
Up to 30 women will take part in this study. Up to 25 participants will take part at MD
Anderson.
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Number of Patients with Increase in s6K Expression
Condition
Endometrial Cancer
Intervention
Metformin
Study Arms / Comparison Groups
Metformin
Description: Metformin 850 mg by mouth once daily for at least 7 days, and up to 30 days before surgery.
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
21
Start Date
September 16, 2010
Completion Date
May 28, 2017
Primary Completion Date
May 28, 2017
Eligibility Criteria
Inclusion Criteria:
1. Patients must have signed informed consent
2. Patients must have histologically-confirmed endometrial adenocarcinoma, any grade (1,
2, or 3) or a mixed tumor with at least an endometrioid component
3. Patients must be a candidate for surgical staging procedure
4. Patients must either be not of child bearing potential or have a negative pregnancy
test within 7 days of treatment. Patients are considered not of child bearing
potential if they are surgically sterile or they are postmenopausal for greater than
12 months
5. Patients must have a documented non-fasting plasma glucose level of less than or equal
to 125 mg/dL. If non-fasting plasma glucose is greater than125 mg/dL, patients must
have a fasting plasma glucose level less than or equal to 125 mg/dL
6. Patients must have an adequated renal function of >60cc/min as documented by the
Cockcroft Gualt creatinine clearance formula: (140 - age) x (weight Kg) DIVIDED BY
Estimated GFR+ 72x serum Creatinine (non-IDMS x 85 (female)
7. Patients must have adequate hepatic function as documented by a serum bilirubin < 2.5
mg/dL, regardless of whether patients have liver involvement secondary to tumor
Exclusion Criteria:
1. Patients with a known history of diabetes mellitus type 1 or 2 or currently taking any
hypoglycemic agents
2. Patients who have received metformin or another mTOR inhibitor in the last 2 years
3. Patients with uterine sarcomas
4. Patients who have received prior treatment for endometrial carcinoma with cytotoxic or
biologic chemotherapy. Patients who have only received hormonal therapy for
endometrial cancer may be included
5. Patients who have undergone definitive surgery including hysterectomy or endometrial
ablation
6. Patients who are not surgical candidates
7. Patients with a known hypersensitivity to metformin
8. Patients with metabolic acidosis, acute or chronic, including ketoacidosis or
increased risk of lactic acidosis
9. Patients who have a history of excessive alcohol use
10. Patients with a history of congestive heart failure requiring pharmacologic treatment
11. Patients with a known history of HIV
12. Patients older than 80 year of age
Gender
Female
Ages
18 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Pamela Soliman, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01205672
Organization ID
2009-0927
Secondary IDs
NCI-2012-01796
Responsible Party
Sponsor
Study Sponsor
M.D. Anderson Cancer Center
Collaborators
American Cancer Society, Inc.
Study Sponsor
Pamela Soliman, MD, Principal Investigator, M.D. Anderson Cancer Center
Verification Date
May 2017