Phase 2
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
Bottom Line
View on ClinicalTrials.gov: NCT02035787 ↗Enrolled (actual)
20
Serious AEs
5.0%
Results posted
Dec 2024
Primary outcome: Primary: Complete Response Rate - 6 Months — 80 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Metformin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Primary completion
- Oct 2023
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 | — |
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.
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.