NCT02035787

Metformin With the Levonorgestrel-Releasing Intrauterine Device for the Treatment of Complex Atypical Hyperplasia (CAH) and Endometrial Cancer (EC) in Non-surgical Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Purpose: This is an open label, single-arm, single-center study of the addition of metformin to standard levonorgestrel-releasing intrauterine device (LR-IUD) treatment of 30 evaluable non-surgical patients with either complex atypical hyperplasia (CAH; n=15) or grade 1 endometrial adenocarcinoma (EC; n=15). Participants:Women, over the age of 18 years, with biopsy-proven CAH/EC who are not candidates for surgical management, and therefore are planned to start standard of care treatment with the LR-IUD Procedures (methods): subjects will be given oral metformin therapy for 12 months, or until disease progression occurs (whichever occurs first), in addition to LR-IUD treatment. Serial endometrial biopsies will be performed, as per standard of care, to assess disease status.

Detailed description

STUDY OBJECTIVES Primary Objective -To compare the rate of CR at 6 months in non-surgical grade 1 EC and CAH patients receiving metformin + LR-IUD to 50% Secondary Objectives * to estimate the rate of CR at 6 months separately in grade 1 EC and CAH patients receiving metformin + LR-IUD * to estimate the rate of CR at 12 months in non-surgical grade 1 EC and CAH patients receiving metformin + LR-IUD * to document patient adherence to long-term (≥3 months) metformin administration * To describe safety of metformin + LR-IUD treatment Exploratory Objectives * To explore changes in cellular proliferation as measured by the marker, Ki-67, from baseline to 6 months * 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 * 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 * To explore association between metabolic factors and metformin concentration levels in tumor tissue/blood/urine and CR at 6 months This is an open label, single-arm, single-center study of the addition of metformin to standard levonorgestrel-releasing intrauterine device (LR-IUD) treatment of 30 evaluable non-surgical patients with either complex atypical hyperplasia (CAH; n=15) or grade 1 endometrial adenocarcinoma (EC; n=15). Women, over the age of 18 years, with biopsy-proven CAH/EC who are not candidates for surgical management, and therefore are planned to start standard of care treatment with the LR-IUD, will be given oral metformin therapy for 12 months, or until disease progression occurs (whichever occurs first), in addition to LR-IUD treatment. Serial endometrial biopsies will be performed, as per standard of care, to assess disease status. We hypothesize that the addition of metformin to standard LR-IUD treatment of CAH and grade 1 EC will result in a complete response (CR) rate at 6 months that is significantly higher than 50% in a population of non-surgical candidates. In addition, we plan to estimate CR rate at 6 months in CAH and EC separately, and in the group as a whole at 12 months. We will also document the rate of patient adherence to long-term metformin therapy.

Conditions

• Complex Atypical Hyperplasia
• Endometrial Cancer

Interventions

Type	Name	Description
DRUG	Metformin	Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device.

Timeline

• Start date: 2014-02-27
• Primary completion: 2023-10-12
• Completion: 2024-04-12
• First posted: 2014-01-14
• Last updated: 2024-12-18
• Results posted: 2024-12-18

Locations

2 sites across 1 country: United States