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

NCT02397083 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: 2014-0944NCI-2015-00919P50CA098258
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

Atypical Endometrial Hyperplasia; FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Response rate (levonorgestrel intrauterine device [LIUD] alone)

  Estimated with a 2-sided 90% confidence interval.

  At 3 months

• Response rate (levonorgestrel intrauterine device [LIUD] alone)

  Estimated with a 2-sided 90% confidence interval.

  6 months

• Response rate for levonorgestrel intrauterine device (LIUD) alone or in combination with everolimus after LIUD failure (i.e., failure to achieve complete response after initial 3 months of LIUD alone)

  Fisher's exact test will be used to compare response rates by 6 months between the LIUD alone arm and the LIUD plus everolimus arm. Estimated on each arm with a 2-sided 90% confidence interval.

  6 months

Secondary Outcomes (4)

• Incidence of adverse events

  Up to 11 years

• Progression free survival

  Up to 11 years

• Overall survival

  Up to 11 years

• Response duration

  Up to 4 weeks after completion of study treatment

Study Arms (2)

Arm I (LIUD)

EXPERIMENTAL

Patients continue treatment with the LIUD for up to 9 months in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Device: Levonorgestrel-Releasing Intrauterine System

Arm II (LIUD, everolimus)

EXPERIMENTAL

Patients continue treatment with the LIUD and receive everolimus PO QD on days 1-28. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Everolimus; Other: Laboratory Biomarker Analysis; Device: Levonorgestrel-Releasing Intrauterine System

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Arm II (LIUD, everolimus)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (LIUD); Arm II (LIUD, everolimus)

Levonorgestrel-Releasing Intrauterine System DEVICE

Placed in the uterus

Also known as: Mirena

Arm I (LIUD); Arm II (LIUD, everolimus)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (18)

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Covenant HealthCare Mackinaw

Saginaw, Michigan, 48604, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

MD Anderson Cancer Center at Cooper-Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Northwell Health

New Hyde Park, New York, 11042, United States

Location

OhioHealth Mansfield Hospital

Mansfield, Ohio, 44903, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

MD Anderson in The Woodlands

Conroe, Texas, 77384, United States

Location

Memorial Hermann Memorial City Medical Center

Houston, Texas, 77024, United States

Location

Lyndon Baines Johnson General Hospital

Houston, Texas, 77026-1967, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Woman's Hospital of Texas

Houston, Texas, 77054, United States

Location

MD Anderson West Houston

Houston, Texas, 77079, United States

Location

MD Anderson League City

League City, Texas, 77573, United States

Location

MD Anderson in Sugar Land

Sugar Land, Texas, 77478, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Shannon N Westin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: March 24, 2015
• Study Start: September 23, 2015
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

US (18)