Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01911247
Recruitment Status : Completed
First Posted : July 30, 2013
Last Update Posted : July 30, 2013
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

The overall goal of this proposal is to investigate the potential benefit of metformin as a novel therapy for the treatment of endometrial cancer. Investigators will evaluate the effect of short-term metformin treatment on the endometrium of obese women with endometrial cancer by comparing each patient's endometrial biopsy before treatment with metformin to their post-treatment hysterectomy specimen.

Participants: Obese women who are to undergo surgical staging for endometrial cancer will also receive short-term treatment (1-4 weeks) with metformin that will continue until the day prior to surgical staging.

The effect of metformin on proliferation, apoptosis and downstream signaling pathways will be compared between pre-treatment endometrial biopsies and post-treatment hysterectomy specimens. Tissue microarrays will be constructed and immunohistochemstry performed to evaluate proliferation, apoptosis and changes in critical signaling pathways mediated by metformin, and these findings will be correlated with our in vitro preclinical studies. Fresh tissue will also be obtained, and Western immunoblotting will be used to assess expression of the phosphorylated forms of the downstream targets of metformin. The hypothesis is that treatment with metformin will result in a decrease in proliferative markers and an increase in markers of apoptosis in the endometrial cancer tumors. AMPK phosphorylation and inhibition of critical downstream targets of the mTOR pathway will be seen in the post-treatment hysterectomy specimens. Metabolomic profiling will also be performed of tumors and associated biofluids (i.e. serum and urine) before and after treatment with metformin to identify potential biomarkers of response to this therapy.


Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Metformin Early Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer
Study Start Date : May 2011
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1 Drug: Metformin
Metformin 850 mg once daily




Primary Outcome Measures :
  1. Change in Ki-67 mean levels between pre-metformin treatment endometrial biopsies and post-metformin treatment hysterectomy specimens [ Time Frame: 4 weeks ]
    The primary null hypothesis of interest, that there is no difference between the pre- and post-treatment Ki-67 mean levels will be evaluated using a paired t-test (two-sided, α<0.05 level). Paired t-tests will also be used to compare pre- and post-treatment measures of secondary endpoints. General linear models will be used to explore the relationship between pre-treatment characteristics (e.g., ER, PR, tumor grade) and change in Ki-67, Ki-max and Ki-min.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be between the ages of 18-75 years old
  • Have a confirmed diagnosis of type I endometrial cancer (endometrioid) based on pre-operative endometrial biopsy or dilation and curettage (D&C)
  • Be obese (BMI greater than or equal to 30) with or without diabetes
  • Have no contraindications to short-term metformin therapy
  • Have a serum creatinine greater 1.0 mg/dL
  • Have normal serum transaminase values (AST and ALT)
  • Need to be able to undergo metformin treatment for a minimum of 1 weeks but no more than a maximum of 4 weeks prior to surgical staging

Exclusion Criteria:

  • Are currently taking metformin or have taken metformin in the past 6 months or have a history of an allergic reaction or intolerance at any time to metformin
  • Have a history of liver or renal dysfunction
  • Have a history of alcoholism
  • Have a history of vitamin B12 deficiency
  • Are pregnant
  • Are currently taking insulin
  • Are currently taking any hormonal therapy or have been on hormonal therapy in the past 4 weeks
  • Are taking a drug that may significantly interact or influence the metabolism of metformin
  • In the opinion of the investigator, the patient is felt not to be appropriate for the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01911247


Locations
Layout table for location information
United States, North Carolina
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Victoria Bae-Jump, M.D. PhD UNC Lineberger Comprehensive Cancer Center

Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01911247     History of Changes
Other Study ID Numbers: LCCC1102
1K23CA143154-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 30, 2013    Key Record Dates
Last Update Posted: July 30, 2013
Last Verified: July 2013

Additional relevant MeSH terms:
Layout table for MeSH terms
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Metformin
Uterine Diseases
Genital Diseases, Female
Hypoglycemic Agents
Physiological Effects of Drugs