Atypical Endometrial Hyperplasia, Stage I Uterine Corpus Cancer AJCC v7, Stage IA Uterine Corpus Cancer AJCC v7, Stage IB Uterine Corpus Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7
Conditions
Brief summary
This phase II trial studies how well levonorgestrel-releasing intrauterine system works in treating patients with complex atypical hyperplasia or grade I endometrial cancer. High levels of estrogen can cause the growth of endometrial cancer cells. Progesterone can help balance the amount of estrogen present. Hormone therapy using levonorgestrel, a type of progesterone, may fight endometrial cancer by helping regulate hormone levels.
Detailed description
PRIMARY OBJECTIVES: I. To determine the efficacy of the levonorgestrel intrauterine device (IUD) (levonorgestrel-releasing intrauterine system) to treat complex atypical hyperplasia (CAH) and grade 1 endometrioid endometrial carcinoma (G1 EEC). II. To determine if response to therapy can be predicted based on the molecular profile of the tumor or by change in gene expression after therapy. SECONDARY OBJECTIVES: I. To assess quality of life outcomes in patients treated with levonorgestrel IUD. II. To document the toxicity profile of the levonorgestrel IUD in the treatment of complex atypical hyperplasia and grade 1 endometrioid endometrial cancer. III. To evaluate the molecular profile of the hysterectomy specimen of patients treated with the levonorgestrel IUD. Compare molecular profile in pretreatment tissue to hysterectomy tissue between responders and non-responders to levonorgestrel IUD therapy. IV. To evaluate long-term survival, disease status, and fertility outcomes in patients with levonorgestrel IUD. OUTLINE: Patients undergo placement of a levonorgestrel-releasing intrauterine system. After completion of study treatment, patients are followed up every 3 months for 1 year, and then periodically for up to 5 years.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Undergo placement of a levonorgestrel-releasing intrauterine system
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients with a diagnosis of complex atypical hyperplasia or endometrial biopsy within three months of study enrollment OR patients with a diagnosis of grade 1 endometrioid endometrial carcinoma on endometrial biopsy within three months of study enrollment in the presence of one or more of the following: 1)desire for future fertility 2)morbid obesity (body mass index \> 40) 3)multiple co-morbidities (ASA Class 3 or 4) * No prior treatment for diagnoses in inclusion criteria 1. * Women of any racial or ethnic group. * Ability to comply with endometrial biopsies every 3 months. * Willing and able to sign informed consent. * Age greater than 18 years.
Exclusion criteria
* Diagnosis of grade 1 endometrioid endometrial carcinoma without the presence of one of the 3 criteria mentioned in inclusion criteria 1. * Diagnosis of grade 2 endometrioid endometrial carcinoma or higher on endometrial biopsy or on dilation and curettage specimen. * Evidence of extrauterine spread of disease on imaging or during surgical evaluation. * Congenital or acquired uterine anomaly which distorts the uterine cavity. * Acute pelvic inflammatory disease. * Acute liver disease or previously diagnosed liver tumor (benign or malignant). * Conditions associated with increased susceptibility to infections with microorganisms. Such conditions include, but are not limited to, AIDS, leukemia and IV drug abuse. * Genital actinomycosis. * Current carcinoma of the breast. * Current pregnancy. * Breastfeeding mothers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate at 12 Month | At 1 year | Will be defined as complete response or partial response based on the endometrial biopsy. |
| Efficacy of the Levonorgestrel Intrauterine Device (IUD) | At 1 year | To determine the efficacy of the Levonorgestrel Intrauterine Device (IUD) to treat complex atypical hyperplasia (CAH) and grade 1 endometrioid endometrial carcinoma (G1 EEC), defined as complete regression disease. The primary efficacy endpoint was pathologic response rate (RR) at 12 months defined as complete response (CR) or partial response (PR). CR was defined as no evidence of cancer or hyperplasia with atypia in patients with (CAH) or EEC. PR was defined as CAH in patients with EEC. Progressive disease (PD) was defined as grade 2 endometrioid endometrial cancer or above in patients with EEC or the presence of any cancer in patients with CAH. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Score Using the Short Form-36 (SF-36) Survey | At baseline, 3 month, 6 month, 9 month and 12 month | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health); 2 summary scores (physical and mental component); and self evaluated change in health status (summary of health status). The score for subscale scores and 2 summary score is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Summary of health status is a 5-point Likert scale ranging from 0=much worse now to 4=much better now. Higher subscale and summary score reflect better health status. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: November 2008- September 2015. All recruitments were done in a medical clinic setting.
Pre-assignment details
69 participants enrolled, 12 participants did not participate on study (9) upgraded pathology, (2) screen failure and (1) withdrew.
Participants by arm
| Arm | Count |
|---|---|
| Levonorgestrel-releasing IUD Single arm study, 52 mg levonorgestrel (Mirena) intrauterine device | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | IUD expulsed | 1 |
| Overall Study | Lost to follow up | 2 |
| Overall Study | Unable to biopsy | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Levonorgestrel-releasing IUD |
|---|---|
| Age, Continuous | 48 years |
| Body mass index (BMI) at diagnosis | 45.5 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Grade 1 Endometrioid Endometrial Cancer (G1EEC) BMI of >40 kg/m2 | 5 Participants |
| Grade 1 Endometrioid Endometrial Cancer (G1EEC) BMI of >40 kg/m2 + multiple comorbidities | 6 Participants |
| Grade 1 Endometrioid Endometrial Cancer (G1EEC) Desires future childbearing +BMI of >40 kg/m2 | 3 Participants |
| Grade 1 Endometrioid Endometrial Cancer (G1EEC) Desires future childbearing + BMI of >40 kg/ m2þmultiple comorbidities | 2 Participants |
| Grade 1 Endometrioid Endometrial Cancer (G1EEC) Desires of future childbearing | 3 Participants |
| Grade 1 Endometrioid Endometrial Cancer (G1EEC) Multiple comorbidities | 2 Participants |
| Menopausal status Menopausal | 25 Participants |
| Menopausal status Premenopausal | 32 Participants |
| Parity Nonparous | 30 Participants |
| Parity Parous | 27 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black | 9 Participants |
| Race/Ethnicity, Customized Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized White | 45 Participants |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 57 |
| other Total, other adverse events | 26 / 57 |
| serious Total, serious adverse events | 0 / 57 |
Outcome results
Primary
Efficacy of the Levonorgestrel Intrauterine Device (IUD)
To determine the efficacy of the Levonorgestrel Intrauterine Device (IUD) to treat complex atypical hyperplasia (CAH) and grade 1 endometrioid endometrial carcinoma (G1 EEC), defined as complete regression disease. The primary efficacy endpoint was pathologic response rate (RR) at 12 months defined as complete response (CR) or partial response (PR). CR was defined as no evidence of cancer or hyperplasia with atypia in patients with (CAH) or EEC. PR was defined as CAH in patients with EEC. Progressive disease (PD) was defined as grade 2 endometrioid endometrial cancer or above in patients with EEC or the presence of any cancer in patients with CAH.
Time frame: At 1 year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Efficacy of the Levonorgestrel Intrauterine Device (IUD) | Stable Disease | 3 Participants |
| Treatment | Efficacy of the Levonorgestrel Intrauterine Device (IUD) | Complete Responders | 37 Participants |
| Treatment | Efficacy of the Levonorgestrel Intrauterine Device (IUD) | Partial Responders | 2 Participants |
| Treatment | Efficacy of the Levonorgestrel Intrauterine Device (IUD) | Progressive Disease | 5 Participants |
Primary
Response Rate at 12 Month
Will be defined as complete response or partial response based on the endometrial biopsy.
Time frame: At 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Response Rate at 12 Month | 83 percentage of participants |
Secondary
Quality of Life Score Using the Short Form-36 (SF-36) Survey
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health); 2 summary scores (physical and mental component); and self evaluated change in health status (summary of health status). The score for subscale scores and 2 summary score is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Summary of health status is a 5-point Likert scale ranging from 0=much worse now to 4=much better now. Higher subscale and summary score reflect better health status.
Time frame: At baseline, 3 month, 6 month, 9 month and 12 month
Population: Number of participants analyzed differ for each row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Physical Functioning Baseline | 61.1 score on a scale | Standard Deviation 31.2 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Physical Functioning 3 month | 65.0 score on a scale | Standard Deviation 30.8 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Physical Functioning 6 month | 69.0 score on a scale | Standard Deviation 29.6 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Physical Functioning 9 month | 68.3 score on a scale | Standard Deviation 33.4 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Physical Functioning 12 month | 66.3 score on a scale | Standard Deviation 31.9 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Physical Baseline | 55.1 score on a scale | Standard Deviation 41.8 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Physical 3 month | 61.9 score on a scale | Standard Deviation 38.8 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Physical 6 month | 69.0 score on a scale | Standard Deviation 41.6 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Physical 9 month | 74.4 score on a scale | Standard Deviation 38.2 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Physical 12 month | 74.3 score on a scale | Standard Deviation 39.3 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Emotional Baseline | 65.3 score on a scale | Standard Deviation 40.9 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Emotional 3 month | 61.6 score on a scale | Standard Deviation 40.3 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Emotional 6 month | 72.4 score on a scale | Standard Deviation 37.2 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Emotional 9 month | 71.7 score on a scale | Standard Deviation 39.6 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Role-Emotional 12 month | 72.1 score on a scale | Standard Deviation 40.5 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Vitality Baseline | 50.0 score on a scale | Standard Deviation 21.2 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Vitality 3 month | 50.1 score on a scale | Standard Deviation 25 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Vitality 6 month | 57.5 score on a scale | Standard Deviation 15 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Vitality 9 month | 56.9 score on a scale | Standard Deviation 21.5 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Vitality 12 month | 51.9 score on a scale | Standard Deviation 26.1 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Mental health Baseline | 67.7 score on a scale | Standard Deviation 21.7 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Mental health 3 month | 67.7 score on a scale | Standard Deviation 22.5 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Mental health 6 month | 73.3 score on a scale | Standard Deviation 18 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Mental health 9 month | 73.1 score on a scale | Standard Deviation 16.8 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Mental health 12 month | 70.5 score on a scale | Standard Deviation 21.4 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Social functioning Baseline | 68.5 score on a scale | Standard Deviation 27.9 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Social functioning 3 month | 67.3 score on a scale | Standard Deviation 29.9 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Social functioning 6 month | 77.7 score on a scale | Standard Deviation 22.3 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Social functioning 9 month | 78.8 score on a scale | Standard Deviation 26.1 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Social functioning 12 month | 72.0 score on a scale | Standard Deviation 28.5 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Pain Baseline | 67.7 score on a scale | Standard Deviation 25.3 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Pain 3 month | 70.5 score on a scale | Standard Deviation 24 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Pain 6 month | 72.0 score on a scale | Standard Deviation 24.3 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Pain 9 month | 73.5 score on a scale | Standard Deviation 24.9 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | Pain 12 month | 70.7 score on a scale | Standard Deviation 23.4 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | General health Baseline | 55.6 score on a scale | Standard Deviation 22.4 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | General health 3 month | 56.8 score on a scale | Standard Deviation 22.2 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | General health 6 month | 60.8 score on a scale | Standard Deviation 21.1 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | General health 9 month | 62.0 score on a scale | Standard Deviation 20 |
| Treatment | Quality of Life Score Using the Short Form-36 (SF-36) Survey | General health 12 month | 60.1 score on a scale | Standard Deviation 19.6 |