Trial record 5 of 26 for:    CAH

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02035787
First received: January 10, 2014
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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 Intervention
Complex Atypical Hyperplasia
Endometrial Cancer
Drug: Metformin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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:
  • adverse event measurement [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    to categorize the type, severity and attribution of all recorded adverse events using CTCAE version 4.0.


Estimated Enrollment: 30
Study Start Date: March 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin, 850 mg. twice daily.
Drug: Metformin
Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device.
Other Name: glucophage

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/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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
  • ECOG Performance Status 0 - 4
  • Non-surgical candidates due to:

    • Desire for fertility preserving treatment
    • Unacceptable surgical risk as defined by:

oAmerican 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 < 60mL/m2) or liver dysfunction (AST/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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02035787

Contacts
Contact: Rachel Phipps, RN 919-966-4432 rachel_phipps@med.unc.edu

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Principal Investigator: Kemi M Doll, MD         
Principal Investigator: Victoria Bae-Jump, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Kemi M Doll, MD UNC Lineberger Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02035787     History of Changes
Other Study ID Numbers: LCCC 1326, 12-0886
Study First Received: January 10, 2014
Last Updated: January 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
metformin
endometrial cancer
Lineberger Comprehensive Cancer Center
complex atypical hyperplasia

Additional relevant MeSH terms:
Endometrial Neoplasms
Sarcoma, Endometrial Stromal
Hyperplasia
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Sarcoma
Neoplasms, Connective and Soft Tissue
Endometrial Stromal Tumors
Pathologic Processes
Levonorgestrel
Metformin
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Hypoglycemic Agents

ClinicalTrials.gov processed this record on July 20, 2014