An Endometrial Cancer Chemoprevention Study of Metformin

NCT01697566 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 2011-07395P50CA098258NCI-2013-00834
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn about the effects of metformin and/or a program called "lifestyle intervention" on the endometrium (inner lining of the uterus) in post-menopausal women who are also obese (both are risk factors for endometrial cancer). Researchers also want to learn how insulin levels will be affected by metformin, diet and/or exercise. Metformin is designed to treat both diabetes and insulin resistance. Insulin resistance is a condition in which the body makes insulin but does not use it properly. It is often referred to as "pre-diabetes". Many people with insulin resistance have high levels of both sugar and insulin in their blood at the same time, which have been reported in patients with endometrial cancer. In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect. Lifestyle intervention is made up of a series of in-person sessions where you meet with a coach to discuss strategies for losing weight and ways to increase physical activity. It also consists of materials designed to help you lose weight and will offer opportunities for supervised exercise.

Conditions

Gynecology

Keywords

Gynecology; Endometrial Cancer Chemoprevention; Obese; Body Mass Index (BMI) >/= 35 kg.m2; Post-menopausal; Hyperinsulinemia; Metformin; Placebo; Sugar pill; Lifestyle intervention; Diet; Exercise

Outcome Measures

Primary Outcomes (2)

• To Evaluate the Participant Body Weight in Pounds (Lbs)

  This study will use a 2 x 2 randomized design with all 100 post- menopausal subjects being randomized to metformin, placebo, placebo and intensive lifestyle intervention, or metformin and intensive lifestyle intervention. Treatments will last 4 months. Participants will be assessed at baseline and end of treatment with endometrial sampling to see if there are changes in the biomarkers.

  Visit 2 (1 week), 4 months, and 1 year

• To Evaluate the Percentage of Ki-67 Positive Cells

  The Q-PCR analyses will be performed in the Quantitative Genomics Core Facility at the University of Texas Medical School at Houston. Over the last 3 years we have used several techniques including differential display, microchip array screening, and real-time quantitative PCR to find such genes. The tools we have developed are directly applicable to the investigation of surrogate endpoint biomarkers (SEBs). Identification of appropriate biomarkers is essential for this study.

  Visit 2 (1 week), 4 months, and 1 year

Secondary Outcomes (2)

• BMI

  Visit 2 (1 week), 4 months, and 1 year

• Weight Loss

  Visit 2 (1 week), 4 months, and 1 year

Study Arms (4)

Metformin

EXPERIMENTAL

Participants gradually increase the dose of metformin by mouth as listed below: Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day After week 4, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg.

Drug: Metformin; Procedure: Endometrial Biopsy; Behavioral: Questionnaires

Placebo + Lifestyle Intervention

EXPERIMENTAL

Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.

Other: Placebo; Procedure: Endometrial Biopsy; Behavioral: Lifestyle Intervention; Behavioral: Questionnaires

Metformin + Lifestyle Intervention

EXPERIMENTAL

Participants gradually increase the dose of metformin by mouth as listed below: Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day After week 4, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.

Drug: Metformin; Procedure: Endometrial Biopsy; Behavioral: Lifestyle Intervention; Behavioral: Questionnaires

Placebo

PLACEBO COMPARATOR

Placebo taken by mouth twice daily for 4, 30 day cycles.

Other: Placebo; Procedure: Endometrial Biopsy; Behavioral: Questionnaires

Interventions

Metformin DRUG

Participants gradually increase the dose of metformin by mouth as listed below: Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day After week 4, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg.

Metformin; Metformin + Lifestyle Intervention

Placebo OTHER

Placebo taken by mouth twice daily for 4, 30 day cycles.

Also known as: sugar pill

Placebo; Placebo + Lifestyle Intervention

Endometrial Biopsy PROCEDURE

Endometrial biopsies obtained at baseline and after 4 months.

Metformin; Metformin + Lifestyle Intervention; Placebo; Placebo + Lifestyle Intervention

Lifestyle Intervention BEHAVIORAL

Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.

Metformin + Lifestyle Intervention; Placebo + Lifestyle Intervention

Questionnaires BEHAVIORAL

Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.

Also known as: surveys

Metformin; Metformin + Lifestyle Intervention; Placebo; Placebo + Lifestyle Intervention

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For this study, only women will be enrolled.
• Body Mass Index (BMI) \> or = 30 kg/m2
• Not frankly diabetic, as measured by a fasting blood glucose \</=126 mg/dL.
• Demonstrate hyperinsulinemia with a QUICK I value \</= 0.357.
• Age \>/= 50 and \</= 65
• Zubrod Performance Scale 0-1
• Hemoglobin \>/= 10 g/dl
• TSH 0.27 - 4.20 µlU/mL
• Menopause as defined as no menses for 1 year and/or FSH \>/= 25.8 mIU/ml
• Must be able to read, write, and speak English.
• Must have a Primary Care Provider (PCP).

You may not qualify if:

• Prior hysterectomy or endometrial ablation
• ALT \>/r = 2.0x Upper Limit of Normal (ULN)
• Serum creatinine \> /= 1.4 mg/dl
• Triglycerides (fasting) \>/ = 400
• Known inability to participate in the ongoing appointments for the four months of the study and scheduled follow-up tests.
• Significant medical or psychiatric history which would make the participant a poor protocol candidate, in the opinion of the principal investigator, for any aspect of study participation including metformin, unsupervised exercise program or dietary behavior change.
• Participant reported history of congestive heart failure
• Prior treatment with Metformin
• Currently being treated for diabetes or meeting criteria for new diagnosis of diabetes.
• Known allergy to Metformin or other biguanide (Proguanil).
• Use of Aromatase Inhibitors, GNRH-agonists i.e.Lupron, Zoladex within the last 6 months
• Use of SERMS (selective estrogen receptor modulators) in the past 6 months, including Tamoxifen and Raloxifene
• Hormone replacement therapy within the last 6 months
• Women who have been treated with chemotherapy for prior malignant disease or currently have an untreated malignancy other than non-melanoma skin cancer
• Patients who have had prior radiation to the pelvis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Obesity; Hyperinsulinism; Motor Activity

Interventions

Metformin; Sugars; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Carbohydrates; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Karen H. Lu, MD
• Organization: M.D. Anderson Cancer Center

khlu@mdanderson.org

713-745-8902

Study Officials

• Karen H. Lu, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2012
• First Posted: October 2, 2012
• Study Start: May 30, 2013
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: June 11, 2025
• Results First Posted: June 11, 2025

Record last verified: 2025-05

Locations

US (1)