Complex Atypical HyperplasiaPhase 2NCT02035787
Metformin With the Levonorgestrel-Releasing Intrauterine Device for the Treatment of Complex Atypical Hyperplasia (CAH) and Endometrial Cancer (EC) in Non-surgical Patients
A Phase 2 study testing Metformin in people with Complex Atypical Hyperplasia and Endometrial Cancer, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Complex Atypical Hyperplasia, Endometrial Cancer
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Feb 2014to 12 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 24Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
TriHealth
Cincinnati, Ohio, 45220
About this study
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.
Read the 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.
- Conditions
- Complex Atypical Hyperplasia, Endometrial Cancer
- Being tested
- Metformin
- Keywords
- metformin, endometrial cancer, Lineberger Comprehensive Cancer Center, complex atypical hyperplasia
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called glucophage
Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin, 850 mg. twice daily. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 6 months
Secondary outcomes (4)
Complete Response Rate by Group
Complete Response is the percentage of individuals achieving complete disease regression as defined by no evidence of microscopic viable hyperplasia or carcinoma on endometrial biopsy in complex atypical hyperplasia and Grade 1 endometrial adenocarcinoma groups. The group are based on the initial treatment assignment and not on the treatment eventually received.
Measured: Up to 6 months
Percent Complete Response Rate-12 Months
Complete Response is the percentage of participants achieving complete disease regression as defined by no evidence of microscopic viable hyperplasia or carcinoma on endometrial biopsy.
Measured: Up to 12 months
Adherence of Treatment
Patients adhered to at least 80% of the scheduled doses throughout the prescribed treatment period. Subjects who achieved a biopsy-proven complete response stopped the treatment early but were still considered adherent to the treatment.
Measured: 12 months
Treatment Attributed Adverse Events
All treatment-attributed adverse events (definite, possible, and probable) with grade information are reported based on The NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2014 (estimated)
- Study start27 Feb 2014
- Primary completion12 Oct 2023
- Study completion12 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Complex Atypical HyperplasiaStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Golfers Against Cancer
- Responsible party
- Sponsor
- Investigators
- Victoria Bae-Jump, MD, PhD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02035787
- Sponsor's protocol ID
- LCCC1326
- Other IDs
- 12-0886
- Status last verified
- Nov 2024
- First submitted
- 10 Jan 2014
- Last updated
- 18 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02035787
- Acronym / sponsor ID
- LCCC1326
- Conditions
- Complex Atypical Hyperplasia, Endometrial Cancer
- Keywords
- metformin, endometrial cancer, Lineberger Comprehensive Cancer Center, complex atypical hyperplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Golfers Against Cancer
- Study start
- 27 Feb 2014 (actual)
- Primary completion
- 12 Oct 2023 (actual)
- Study completion
- 12 Apr 2024 (actual)
- First posted
- 14 Jan 2014 (estimated)
- Results
- Posted 18 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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/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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminMetformin, 850 mg. twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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:
- AND
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: glucophageMetformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device. | Drug | Metformin |
Primary outcome
Complete Response Rate - 6 Months
Time frame: Up to 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.
4 secondary outcomes
Complete Response Rate by Group
Time frame: Up to 6 months
Percent Complete Response Rate-12 Months
Time frame: Up to 12 months
Adherence of Treatment
Time frame: 12 months
Treatment Attributed Adverse Events
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
Related trials for Complex Atypical Hyperplasia
Active, not recruitingPhase 2
Levonorgestrel-Releasing Intrauterine System in Treating Patients With Complex Atypical Hyperplasia or Grade I Endometrial Cancer
Atypical Endometrial Hyperplasia, Stage I Uterine Corpus Cancer AJCC v7
Active, not recruitingPhase 2
Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer
Atypical Endometrial Hyperplasia, FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
RecruitingObservational study
The DETECT Study: Discovery and Evaluation of Testing for Endometrial and Ovarian Cancer in Tampons
Endometrial Cancer, Endometrial Cancer Precursors
Active, not recruitingPhase 2
Improving the Treatment for Women With Early Stage Cancer of the Uterus
Complex Endometrial Hyperplasia With Atypia, Grade 1 Endometrial Endometrioid Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victoria Bae-Jump, MD, PhD principal investigator
UNC Lineberger Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Complex Atypical Hyperplasia and Endometrial Cancer, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response Rate - 6 Months (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.