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

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center
• Treatments: Levonorgestrel; Metformin

Criteria

Inclusion Criteria:

Subjects must meet all of the inclusion criteria to participate in this study:

• Histologically confirmed CAH or grade 1 EC

• Females age ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 4

• Non-surgical candidates due to:

• Desire for fertility preserving treatment

• Unacceptable surgical risk as defined by:

• American Society of Anesthesiologists Physical Status (ASA) ≥ 4 and/or Perioperative Cardiac Risk > 5%(45) and/or Perioperative Respiratory Failure Risk > 5%(46)

AND

oIndependent medicine or cardiology pre-op consultation concluding 'high' surgical risk.

• Planned treatment with the LR-IUD for CAH or grade 1 EC by primary physician

• Women of childbearing potential (WOCBP) must have negative pregnancy test within 7 days of D1 of treatment

• Understand study design, risks, and benefits and have signed informed consent

Exclusion Criteria Any patient meeting any of the exclusion criteria at baseline will be excluded from study participation.

• Evidence of renal dysfunction (Cr > 1.5mg/dL or Cr clearance < 60 mL/m2) or liver dysfunction (AST/alanine aminotransferase (ALT) > 2x upper limit of normal (ULN))

• Currently receiving progestin therapy (local, topical, or systemic)

• Myometrial invasion >50% or evidence of nodal or metastatic disease on baseline MRI (MRI only to be done for EC patients) or tumor size > 2cm on MRI or pelvic ultrasound

• Mixed histology including clear cell, serous, undifferentiated or sarcomatous elements

• Prior or current use of metformin within the past 3 months

• History of hypersensitivity to metformin or history of discontinuation secondary to attributed adverse effects

• Chronic (daily use for > 1 month) use of cimetidine (significant increase in metformin concentration and risk of lactic acidosis)

• Iodinated contrast agents used in prior 48 hours (significant increase in metformin concentration and risk of lactic acidosis)

• Pregnant or lactating

• Recent (< 4 weeks) active, documented, cervical infection