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

NCT ID: NCT02035787

Last Updated: 2024-12-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-27

Study Completion Date

2024-04-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Complex Atypical Hyperplasia Endometrial Cancer

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

metformin endometrial cancer Lineberger Comprehensive Cancer Center complex atypical hyperplasia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Metformin

Metformin, 850 mg. twice daily.

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Metformin

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

glucophage

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Golfers Against Cancer

UNKNOWN

Sponsor Role collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Victoria Bae-Jump, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

TriHealth

Cincinnati, Ohio, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

12-0886

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC1326

Identifier Type: -

Identifier Source: org_study_id