A Phase 2 interventional study of Metformin in Complex Atypical Hyperplasia and Endometrial Cancer, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 2 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-18.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
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.
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
Exploratory Objectives
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.
1,347 studies on the registry are indexed under Endometrial Neoplasms; 452 are open to participants now.
This study's enrollment of 20 is below the median of 70 across 954 interventional studies indexed under Endometrial Neoplasms.
Browse Endometrial Neoplasms studies →UNC Lineberger Comprehensive Cancer Center is the lead sponsor of 424 studies on the registry; 96 are open to participants now.
Of its 33 completed or terminated interventional studies of FDA-regulated products, 26 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Subjects must meet all of the inclusion criteria to participate in this study:
Non-surgical candidates due to:
Unacceptable surgical risk as defined by:
AND
oIndependent medicine or cardiology pre-op consultation concluding 'high' surgical risk.
Exclusion Criteria Any patient meeting any of the exclusion criteria at baseline will be excluded from study participation.
Metformin, 850 mg. twice daily.
Drug: Metformin
Metformin added to standard non-surgical treatment with levonorgestrel-Releasing Intrauterine Device.
Also known as: glucophage
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.
Time frame: Up to 6 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months
Subjects were enrolled in the study between 02/27/2014 and 10/12/2023, at three sites in the United States.
| Milestone | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma |
|---|---|---|
| Started | 12 | 8 |
| Completed | 4 | 6 |
| Not completed | 8 | 2 |
| Withdrew: Adverse event | 3 | 0 |
| Withdrew: Complete response | 4 | 1 |
| Withdrew: Protocol violation | 1 | 1 |
| Milestone | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma |
|---|---|---|
| Started | 12 | 8 |
| Completed | 7 | 7 |
| Not completed | 5 | 1 |
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.
| percentage of participants | Whole Group |
|---|---|
| Complete Response Rate - 6 Months | 80 (52 to 96) |
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.
| percentage of participants | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma |
|---|---|---|
| Complete Response Rate by Group | 100 (72 to 100) | 40 (5 to 85) |
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.
| percentage of participants | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma. |
|---|---|---|
| Percent Complete Response Rate-12 Months | 100 (74 to 100) | 60 (23 to 88) |
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.
| Participants | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma |
|---|---|---|
| Adherence of Treatment | 10 | 7 |
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.
| Participants | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma. |
|---|---|---|
| Abdominal pain Grade1 | 0 | 1 |
| Abdominal pain Grade 2 | 0 | 1 |
| Alanine aminotransferase increased Grade1 | 2 | 1 |
| Alanine aminotransferase increased Grade 2 | 0 | 1 |
| Anorexia Grade1 | 2 | 1 |
| Anxiety Grade2 | 1 | 1 |
| Aspartate aminotransferase increased Grade1 | 2 | 1 |
| Aspartate aminotransferase increased Grade2 | 0 | 1 |
| Blood and lymphatic system disorders - Other, specify Grade1 | 2 | 1 |
| Blood and lymphatic system disorders - Other, specify Grade2 | 0 | 1 |
| Diarrhea Grade 1 | 4 | 3 |
| Diarrhea Grade 2 | 2 | 1 |
| Diarrhea Grade 3 | 1 | 0 |
| Dizziness Grade 2 | 1 | 1 |
| Headache Grade1 | 1 | 0 |
| Headache Grade2 | 1 | 0 |
| Fatigue Grade1 | 0 | 1 |
| Insomnia Grade1 | 0 | 1 |
| Nausea Grade1 | 8 | 4 |
| Nausea Grade2 | 2 | 0 |
| Reproductive system and breast disorders - Other, specify Grade1 | 1 | 0 |
| Stomach pain Grade1 | 0 | 1 |
| Vaginal hemorrhage Grade1 | 1 | 0 |
| Vaginal discharge Grade1 | 0 | 1 |
| Vomiting Grade 3 | 1 | 0 |
Collected over Up to 13 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Complex Atypical Hyperplasia | 0/12 (0%) | 0/12 (0%) | 12/12 (100%) |
| Grade 1 Endometrial Adenocarcinoma | 0/8 (0%) | 1/8 (12.5%) | 8/8 (100%) |
| Event | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma |
|---|---|---|
| Renal calculiRenal and urinary disorders | 0/12 | 1/8 |
| Event | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma |
|---|---|---|
| NauseaGastrointestinal disorders | 10/12 | 4/8 |
| DiarrheaGastrointestinal disorders | 7/12 | 4/8 |
| InsomniaPsychiatric disorders | 0/12 | 3/8 |
| Blood and lymphatic system disorders - Other, specifyBlood and lymphatic system disorders | 2/12 | 2/8 |
| Abdominal painGastrointestinal disorders | 0/12 | 2/8 |
| Alanine aminotransferase increasedInvestigations | 2/12 | 2/8 |
| Aspartate aminotransferase increasedInvestigations | 2/12 | 2/8 |
| AnorexiaMetabolism and nutrition disorders | 2/12 | 1/8 |
| HeadacheNervous system disorders | 2/12 | 1/8 |
| DyspepsiaGastrointestinal disorders | 0/12 | 1/8 |
Subjects with biopsy-proven complex atypical hyperplasia or grade 1 endometrial carcinoma.
| Age, Continuous(years) | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma | Total |
|---|---|---|---|
| Mean | 40.5 ± 16.77 | 42.75 ± 17.87 | 41.4 ± 16.78 |
| Sex: Female, Male(Participants) | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma | Total |
|---|---|---|---|
| Female | 12 | 8 | 20 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 |
| Not Hispanic or Latino | 11 | 8 | 19 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 1 | 4 |
| White | 8 | 7 | 15 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Complex Atypical Hyperplasia | Grade 1 Endometrial Adenocarcinoma | Total |
|---|---|---|---|
| United States | 12 | 8 | 20 |
Documents are hosted by the registry — open the source record to download them.
Ran from Feb 2014 to primary completion in Oct 2023, 115 months.
Results were first posted in Dec 2024, 1 year 2 months after primary completion.
Of 105 non-industry phase 2 interventional studies under Endometrial Neoplasms, half reached primary completion within 58 months of starting (the median), counting those still running; a quarter within 40 and three quarters within 113. This study's 115 months is above that.
Counting every sponsor, half of 138 studies reached it within 54 months; a quarter within 37 and three quarters within 113.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Metformin
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