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

NCT02035787 | Completed Phase 2 Results DMC

• 2 other identifiers: LCCC132612-0886
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Complex Atypical Hyperplasia; Endometrial Cancer

Keywords

metformin; endometrial cancer; Lineberger Comprehensive Cancer Center; complex atypical hyperplasia

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate - 6 Months

  Complete Response is subjects with complex atypical hyperplasia or Grade 1 endometrial adenocarcinoma percentage of individuals achieved complete disease regression as defined by no evidence of microscopic viable hyperplasia or carcinoma on endometrial biopsy.

  Up to 6 months

Secondary Outcomes (4)

• Complete Response Rate by Group

  Up to 6 months

• Percent Complete Response Rate-12 Months

  Up to 12 months

• Adherence of Treatment

  12 months

• Treatment Attributed Adverse Events

  Up to 12 months

Study Arms (1)

Metformin

EXPERIMENTAL

Metformin, 850 mg. twice daily.

Drug: Metformin

Interventions

Metformin DRUG

Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device.

Also known as: glucophage

Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Golfers Against Cancer: collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

TriHealth

Cincinnati, Ohio, 45220, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Lauren Higgins
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

lqhiggin@ad.unc.edu

919- 966-4432

Study Officials

• Victoria Bae-Jump, MD, PhD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: January 14, 2014
• Study Start: February 27, 2014
• Primary Completion: October 12, 2023
• Study Completion: April 12, 2024
• Last Updated: December 18, 2024
• Results First Posted: December 18, 2024

Record last verified: 2024-11

Locations

US (2)