Overview

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

Status:
Recruiting
Trial end date:
2026-09-30
Target enrollment:
0
Participant gender:
Female
Summary
This randomized phase II trial studies how well levonorgestrel-releasing intrauterine system works when given alone or with everolimus in treating patients with atypical hyperplasia (a pre-cancerous growth of the lining of the uterus) or stage IA grade 1 endometrial cancer. The levonorgestrel-releasing intrauterine system is designed to prevent pregnancy by releasing a hormone called levonorgestrel, which is a type of progesterone. Progesterone is a common type of hormone that is used to prevent pregnancy and may prevent or slow tumor cell growth. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether the levonorgestrel-releasing intrauterine system works better with or without everolimus in treating patients with atypical hyperplasia or stage IA grade 1 endometrial cancer.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborators:
National Cancer Institute (NCI)
Novartis
Treatments:
Everolimus
Levonorgestrel
Sirolimus
Criteria
Inclusion Criteria:

- 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

Exclusion Criteria:

- Patients with grade 2-3 endometrioid, uterine serous, clear cell, mucinous, squamous,
transitional cell, sarcomas, or carcinosarcoma histology

- Evidence of extrauterine spread of disease on imaging or during surgical evaluation

- 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 intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g.
sirolimus, temsirolimus)

- Known intolerance or hypersensitivity to progesterone or its excipients

- 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

- 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

- 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 a known history of human immunodeficiency virus (HIV) seropositivity

- 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

- 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

- Congenital or acquired uterine anomaly which distorts the uterine cavity

- Genital actinomycosis

- 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

- Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 1 month prior to dosing

- Women who are pregnant or nursing (lactating) women

- 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