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

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

Overview[ - collapse ][ - ]

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	Complex Atypical Hyperplasia Endometrial Cancer
Intervention	Drug: Metformin
Phase	N/A
Sponsor	UNC Lineberger Comprehensive Cancer Center
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

Tracking Information[ + expand ][ + ]

First Received Date	January 10, 2014
Last Updated Date	January 13, 2014
Start Date	March 2014
Estimated Primary Completion Date	March 2017
Current 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%
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	Metformin With the Levonorgestrel-Releasing Intrauterine Device for the Treatment of Complex Atypical Hyperplasia (CAH) and Endometrial Cancer (EC) in Non-surgical Patients
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
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.
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.
Study Type	Interventional
Study Phase	N/A
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Complex Atypical Hyperplasia Endometrial Cancer
Intervention	Drug: Metformin Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device. Other Names: glucophage
Study Arm (s)	Experimental: Metformin Metformin, 850 mg. twice daily.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	30
Estimated Completion Date	March 2017
Estimated Primary Completion Date	March 2016
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 - 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
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Rachel Phipps, RN 919-966-4432 rachel_phipps@med.unc.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT02035787
Other Study ID Numbers	LCCC 1326
Has Data Monitoring Committee	Yes
Information Provided By	UNC Lineberger Comprehensive Cancer Center
Study Sponsor	UNC Lineberger Comprehensive Cancer Center
Collaborators	Not Provided
Investigators	Principal Investigator: Kemi M Doll, MD UNC Lineberger Comprehensive Cancer Center
Verification Date	January 2014

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