Metformin and Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
American Cancer Society, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01205672
First received: September 17, 2010
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.

Condition Intervention
Endometrial Cancer
Drug: Metformin

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Molecular Effects of Metformin on the Endometrium in Patients With Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patients with Increase in s6K Expression [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2010
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin 850 mg by mouth once daily for at least 7 days, and up to 30 days before surgery.
Drug: Metformin
850 mg by mouth once daily for at least 7 days, and up to 30 days before surgery.

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01205672

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
American Cancer Society, Inc.
Investigators
Principal Investigator: Pamela Soliman, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01205672     History of Changes
Other Study ID Numbers: 2009-0927
Study First Received: September 17, 2010
Last Updated: December 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Endometrium
Gynecologic malignancy
Endometrial adenocarcinoma
Insulin/glucose metabolism
Metformin

Additional relevant MeSH terms:
Endometrial Neoplasms
Sarcoma, Endometrial Stromal
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Sarcoma
Neoplasms, Connective and Soft Tissue
Endometrial Stromal Tumors
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014