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Trial record 1 of 1 for:    LCCC 1326
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Metformin With the Levonorgestrel-Releasing Intrauterine Device for the Treatment of Complex Atypical Hyperplasia (CAH) and Endometrial Cancer (EC) in Non-surgical Patients

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ClinicalTrials.gov Identifier: NCT02035787
Recruitment Status : Recruiting
First Posted : January 14, 2014
Last Update Posted : March 17, 2023
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Study Description
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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.


Condition or disease Intervention/treatment Phase
Complex Atypical Hyperplasia Endometrial Cancer Drug: Metformin Not Applicable

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Metformin With the Levonorgestrel-Releasing Intrauterine Device for the Treatment of Complex Atypical Hyperplasia (CAH) and Endometrial Cancer (EC) in Non-surgical Patients
Actual Study Start Date : February 27, 2014
Estimated Primary Completion Date : July 2028
Estimated Study Completion Date : February 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Metformin
Metformin, 850 mg. twice daily.
 Drug: Metformin
Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device.
Other Name: glucophage


Outcome Measures
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Primary Outcome Measures :
  1. Response rate [ Time Frame: 6 months ]
    percent of individuals achieving complete disease regression as defined by no evidence of microscopic viable hyperplasia or carcinoma on endometrial biopsy after 6 months of treatment compared to a base rate of 50%


Secondary Outcome Measures :
  1. adverse event measurement [ Time Frame: 12 months ]
    to categorize the type, severity and attribution of all recorded adverse events using CTCAE version 4.0.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02035787


Contacts
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Contact: Melisa Ramirez-Pineda 919-966-4432 melisa_ramirez-pineda@med.unc.edu
Contact: Jada Jones 919-966-4432 jojada@email.unc.edu

Locations
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United States, North Carolina
Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Melisa Ramirez-Pineda    919-966-4432    melisa_ramirez-pineda@med.unc.edu   
Contact: Jada Jones    919-966-4432    jojada@email.unc.edu   
Principal Investigator: Victoria Bae-Jump, MD         
United States, Ohio
TriHealth Recruiting
Cincinnati, Ohio, United States, 45220
Principal Investigator: Robert Neff, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
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Principal Investigator: Victoria Bae-Jump, MD, PhD UNC Lineberger Comprehensive Cancer Center
More Information
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Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02035787    
Other Study ID Numbers: LCCC 1326
12-0886 ( Other Identifier: IRB )
First Posted: January 14, 2014    Key Record Dates
Last Update Posted: March 17, 2023
Last Verified: March 2023
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
metformin
endometrial cancer
Lineberger Comprehensive Cancer Center
complex atypical hyperplasia
Additional relevant MeSH terms:
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Endometrial Neoplasms
Hyperplasia
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
Pathologic Processes
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs