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

Primary Purpose

Endometrial Cancer

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Metformin

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring Endometrium, Gynecologic malignancy, Endometrial adenocarcinoma, Insulin/glucose metabolism, Metformin

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have signed informed consent
Patients must have histologically-confirmed endometrial adenocarcinoma, any grade (1, 2, or 3) or a mixed tumor with at least an endometrioid component
Patients must be a candidate for surgical staging procedure
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
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
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)
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:

Patients with a known history of diabetes mellitus type 1 or 2 or currently taking any hypoglycemic agents
Patients who have received metformin or another mTOR inhibitor in the last 2 years
Patients with uterine sarcomas
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
Patients who have undergone definitive surgery including hysterectomy or endometrial ablation
Patients who are not surgical candidates
Patients with a known hypersensitivity to metformin
Patients with metabolic acidosis, acute or chronic, including ketoacidosis or increased risk of lactic acidosis
Patients who have a history of excessive alcohol use
Patients with a history of congestive heart failure requiring pharmacologic treatment
Patients with a known history of HIV
Patients older than 80 year of age

Sites / Locations

Lyndon B. Johnson General Hospital
University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metformin

Arm Description

Metformin 850 mg by mouth once daily for at least 7 days, and up to 30 days before surgery.

Outcomes

Primary Outcome Measures

Number of Patients with Increase in s6K Expression

Baseline expression of s6K measured using Western blots, which yield ordinal results (e.g. "weak", "moderate", "strong", etc.). After treatment with metformin, expression again observed, and the percent of patients who have an increase in expression will be calculated.

Secondary Outcome Measures

Full Information

NCT ID

NCT01205672

First Posted

September 17, 2010

Last Updated

May 31, 2017

Sponsor

M.D. Anderson Cancer Center

Collaborators

American Cancer Society, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01205672

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

September 16, 2010 (Actual)

Primary Completion Date

May 28, 2017 (Actual)

Study Completion Date

May 28, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

American Cancer Society, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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: To describe the effects of metformin on the histology and proliferation of the endometrium in women with endometrial cancer. To assess the effect of body mass index on the response to treatment with metformin To assess the effect of insulin resistance on the response to treatment with metformin 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endometrial Cancer

Keywords

Endometrium, Gynecologic malignancy, Endometrial adenocarcinoma, Insulin/glucose metabolism, Metformin

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Metformin 850 mg by mouth once daily for at least 7 days, and up to 30 days before surgery.

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

850 mg by mouth once daily for at least 7 days, and up to 30 days before surgery.

Primary Outcome Measure Information:

Title

Number of Patients with Increase in s6K Expression

Description

Time Frame

30 days

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have signed informed consent Patients must have histologically-confirmed endometrial adenocarcinoma, any grade (1, 2, or 3) or a mixed tumor with at least an endometrioid component Patients must be a candidate for surgical staging procedure 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 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 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) 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: Patients with a known history of diabetes mellitus type 1 or 2 or currently taking any hypoglycemic agents Patients who have received metformin or another mTOR inhibitor in the last 2 years Patients with uterine sarcomas 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 Patients who have undergone definitive surgery including hysterectomy or endometrial ablation Patients who are not surgical candidates Patients with a known hypersensitivity to metformin Patients with metabolic acidosis, acute or chronic, including ketoacidosis or increased risk of lactic acidosis Patients who have a history of excessive alcohol use Patients with a history of congestive heart failure requiring pharmacologic treatment Patients with a known history of HIV Patients older than 80 year of age

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pamela Soliman, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lyndon B. Johnson General Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77026

Country

United States

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

UT MD Anderson Cancer Center website

Learn more about this trial

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

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