Preoperative Window Study of Metformin for the Treatment of Endometrial Cancer

NCT01911247 | Completed Early Phase 1

• 2 other identifiers: LCCC11021K23CA143154-01A1
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Change in Ki-67 mean levels between pre-metformin treatment endometrial biopsies and post-metformin treatment hysterectomy specimens

  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.

  4 weeks

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: Metformin

Interventions

Metformin DRUG

Metformin 850 mg once daily

Arm 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Bateman NW, Teng PN, Hope E, Hood BL, Oliver J, Ao W, Zhou M, Wang G, Tommarello D, Wilson K, Litzy T, Conrads KA, Hamilton CA, Darcy KM, Casablanca Y, Maxwell GL, Bae-Jump V, Conrads TP. Jupiter microtubule-associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers. Cancer Med. 2020 Feb;9(3):1092-1103. doi: 10.1002/cam4.2729. Epub 2019 Dec 6.

  PMID: 31808620 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Victoria Bae-Jump, M.D. PhD

  UNC Lineberger Comprehensive 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: July 23, 2013
• First Posted: July 30, 2013
• Study Start: May 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: July 30, 2013

Record last verified: 2013-07

Locations

US (1)