This early phase I trial studies how well metformin hydrochloride works when added to levonorgestrel-releasing intrauterine system in treating patients with atypical endometrial hyperplasia or endometrial cancer who cannot undergo surgery. Metformin hydrochloride is a widely-used type II diabetes drug that may also stop cancer cells from dividing. Estrogen may cause cancer. Levonorgestrel-releasing intrauterine system is a device placed in the uterus that reduces the level of estrogen in the body. Giving metformin hydrochloride in addition to treatment with levonorgestrel-releasing intrauterine system may be an effective alternative for patients with atypical endometrial hyperplasia or endometrial cancer who cannot undergo surgery.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02035787.
PRIMARY OBJECTIVE:
I. To compare the rate of complete response (CR) at 6 months in non-surgical grade 1 endometrial cancer (EC) and complex atypical hyperplasia (CAH) patients receiving metformin (metformin hydrochloride) + levonorgestrel-releasing intrauterine device (LR-IUD) to 50%.
SECONDARY OBJECTIVES:
I. To estimate the rate of CR at 6 months separately in grade 1 EC and CAH patients receiving metformin + LR-IUD.
II. To estimate the rate of CR at 12 months in non-surgical grade 1 EC and CAH patients receiving metformin + LR-IUD.
III. To document patient adherence to long-term (>= 3 months) metformin administration.
IV. To describe safety of metformin + LR-IUD treatment.
EXPLORATORY OBJECTIVES:
I. To explore changes in cellular proliferation as measured by the marker, marker of proliferation Ki-67 (Ki-67), from baseline to 6 months.
II. To explore association between the level of expression of the metformin transporter proteins and key targets of the metformin/mammalian target of rapamycin (mTOR) signaling pathway and CR status at 6 months.
III. To perform a comprehensive unbiased profiling of metabolites by analyzing the metabolic “fingerprints” of the biofluids (i.e. serum and urine) and “footprints” of the tumor tissue pre- and post- 6 months of metformin treatment.
IV. To explore association between metabolic factors and metformin concentration levels in tumor tissue/blood/urine and CR at 6 months.
OUTLINE:
Beginning within 30 days of standard of care dilation and curettage (D & C) and levonorgestrel-releasing intrauterine system placement, patients receive metformin hydrochloride orally (PO) twice daily (BID) (titrated from once daily [QD] within 1 month [30 days]) for 12 months in the absence in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at up to 30 days.
Lead OrganizationUNC Lineberger Comprehensive Cancer Center
Principal InvestigatorVictoria Lin Bae-Jump
