Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer

Prior treatment

• Patients who have prior therapy with everolimus or any other mammalian target of rapamycin (mTOR) inhibitor
• Patients currently receiving anticancer therapies (including chemotherapy, radiation therapy, hormonal, or antibody-based therapy); prior treatment should have a washout period of 28 days or 4 1/2 half-lives (7 days), whichever is shorter
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus (e.g., inability to take oral medication or a requirement for intravenous \[IV\] alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow the capsule whole
• Patients who have any severe and/or uncontrolled medical conditions such as: a) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =\< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; b) symptomatic congestive heart failure of New York Heart Association class III or IV; c) active (acute or chronic) or uncontrolled severe infection (not responding to antibiotics), liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus-deoxyribonucleic acid \[HBV-DNA\] and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable hepatitis C virus-ribonucleic acid \[HCV-RNA\]); d) known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide \[DLCO\] 50% or less of normal and oxygen \[O2\] saturation 88% or less at rest on room air); e) active, bleeding diathesis
• Chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed
• Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
• Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
• Women of child-bearing potential (WOCBP), defined as women physiologically capable of becoming pregnant, must use one additional highly effective methods of contraception in addition to the LIUD during the study and 8 weeks after; acceptable effective contraception methods include combo of the following: a) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; b) total abstinence or; c) male/female sterilization; women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation \> six weeks prior to randomization; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
• Women who are on contraindicated medications to everolimus must have confirmation from their physician that they may change or discontinue the medication if randomized to the LIUD + everolimus arm

Other illness

• Evidence of extrauterine spread of disease on imaging or during surgical evaluation
• Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
• Known intolerance or hypersensitivity to progesterone or its excipients
• Patients who have a known history of human immunodeficiency virus (HIV) seropositivity
• Other malignancies within the past 3 years except for basal or squamous cell carcinoma of the skin
• Active (acute or chronic) or uncontrolled severe infections (not responding to antibiotics), including acute pelvic inflammatory disease
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

Lab values

• Uncontrolled diabetes mellitus as defined by glycosylated hemoglobin (HbA1c) \> 8% despite adequate therapy; patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary

Other

• Patients with grade 2-3 endometrioid, uterine serous, clear cell, mucinous, squamous, transitional cell, sarcomas, or carcinosarcoma histology
• Congenital or acquired uterine anomaly which distorts the uterine cavity
• Genital actinomycosis
• Women who are pregnant or nursing (lactating) women

• All patients with a diagnosis of complex atypical hyperplasia OR, grade 1 endometrioid OR focal grade 2 adenocarcinoma in predominately grade 1 disease endometrial carcinoma on endometrial biopsy or dilation and curettage (D \& C) within three months of study enrollment
• Patients with complex atypical hyperplasia OR grade 1 endometrioid adenocarcinoma with stable/persistent disease with LIUD already in place. LIUD must have been in place for at least 3 months
• Prior progesterone treatment is ALLOWED, but a 28 day washout period is required before LIUD placement. If archival tissue is available from prior to any progesterone treatment, the washout period is not needed
• Ability to comply with endometrial biopsies every 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin (Hb) \> 9 g/dL
• Total serum bilirubin =\< 2.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN)
• International normalized ratio (INR) =\< 2; factor 10A drawn if patient on anticoagulant Eliquis
• Serum creatinine =\< 1.5 x ULN
• Fasting serum cholesterol =\< 300 mg/dL OR =\< 7.75 mmol/L AND fasting triglycerides =\< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
• Signed informed consent obtained prior to any screening procedures