Phase 2
Completed N=20
Metformin With the Levonorgestrel-Releasing Intrauterine Device for the Treatment of Complex Atypical Hyperplasia (CAH) and Endometrial Cancer (EC) in Non-surgical Patients
Complex Atypical Hyperplasia · Endometrial Cancer
Source: ClinicalTrials.gov NCT02035787 ↗
Enrolled (actual)
20
Serious AEs
5.0%
Results posted
Dec 2024
Primary outcomePrimary: Complete Response Rate - 6 Months — 80 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Complete Response Rate - 6 Months |
80 | — |
| SECONDARY Complete Response Rate by Group |
100; 40 | — |
| SECONDARY Percent Complete Response Rate-12 Months |
100; 60 | — |
| SECONDARY Adherence of Treatment |
10; 7 | — |
| SECONDARY Treatment Attributed Adverse Events |
0; 1; 0; 1; 2; 1 | — |
Eligibility 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 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
Data sourced from ClinicalTrials.gov (NCT02035787). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.