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

NCT01205672 | Completed Early Phase 1 FDA Drug

• 3 other identifiers: 2009-0927NCI-2012-01796CBC 965712
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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. 1.To describe the effects of metformin on the histology and proliferation of the endometrium in women with endometrial cancer.
2. 2.To assess the effect of body mass index on the response to treatment with metformin
3. 3.To assess the effect of insulin resistance on the response to treatment with metformin
4. 4.To determine effects of metformin on the serum, urine and DNA biomarkers of women with endometrial cancer.

Conditions

Endometrial Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  30 days

Study Arms (1)

Metformin

EXPERIMENTAL

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

Drug: Metformin

Interventions

Metformin DRUG

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

Metformin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• American Cancer Society, Inc.: collaborator

Study Sites (2)

Lyndon B. Johnson General Hospital

Houston, Texas, 77026, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Endometrial Neoplasms; Insulin Resistance

Interventions

Metformin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Pamela Soliman, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: September 20, 2010
• Study Start: September 16, 2010
• Primary Completion: May 28, 2017
• Study Completion: May 28, 2017
• Last Updated: June 2, 2017

Record last verified: 2017-05

Locations

US (2)