Evaluation of the Molecular Effects of Metformin on the Endometrium in Patients With Endometrial Cancer

• Status: Completed
• Trial end date: 2017-05-28
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: American Cancer Society, Inc.
• Treatments: Metformin

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