Clinical trial NCT01205672: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Endometrial Cancer
Keywords: Endometrium
Gynecologic malignancy
Endometrial adenocarcinoma
Insulin/glucose metabolism
Metformin
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: American Cancer Society, Inc.
First posted: 2010-09-20
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients with Increase in s6K Expression
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Lyndon B. Johnson General Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Pamela Soliman, MD
role: PRINCIPAL_INVESTIGATOR
References: