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

Atypical Endometrial Hyperplasia Clinical Trial

Official title: Phase II Study of the Levonorgestrel Intrauterine Device Alone or in Combination With the mTORC1 Inhibitor, Everolimus, for the Treatment of Complex Atypical Hyperplasia and Stage Ia Grade 1 Endometrial Cancer

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Estimate the efficacy of the levonorgestrel intrauterine device (LIUD) (levonorgestrel-releasing intrauterine system) alone to treat complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial carcinoma with response rate.

II. Estimate the efficacy of the LIUD in combination with everolimus to treat LIUD-refractory complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial carcinoma with response rate.

SECONDARY OBJECTIVES:

I. Document the toxicity profile of the levonorgestrel intrauterine device alone or in combination with everolimus using the National Institutes of Health-National Cancer Institute (NIH-NCI) Common Terminology Criteria for Adverse Events version (v) 4.0.

II. Estimate overall survival (OS) and event-free survival (EFS) of patients with complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial cancer treated with the levonorgestrel IUD alone or in combination with everolimus.

III. Estimate the response duration associated with the levonorgestrel IUD alone or in combination with everolimus in patients with complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial cancer.

EXPLORATORY OBJECTIVE:

I. Determine if response to therapy can be predicted based on the molecular profile of the tumor, including estrogen-induced genes and relevant pathway members, or by change in gene expression after therapy.

OUTLINE:

First Stage

• If D&C confirms EEC grade 1 or CAH-patient enrolled

• If the patient is found to have stable disease at 3 months continue on to the second stage of the study to be randomized.

• If the patient has a complete response at 3 months; EMB 3 months later to confirm complete response.

• Once complete response confirmed, patient Continues EMB every 6-12 months until disease progression per provider.

• If the patient has progressive disease at 3 months- OFF STUDY Second Stage

• Patients with stable disease at and 3 month EMB, recurrent disease at a subsequent EMB, or entering protocol with outside IUD in place showing stable disease demonstrating progesterone resistance

LIUD Only Arm

• Visits every 3 months

• EMB at 6 months

• if regression/SD: continue on study

• EMB at 9 months and 1 year:

• Off study for PD or D&C at MD's discretion

• SD at 1 year: off study

• CR at 1 year: SOC EMB 3 months later then Q6 months if confirmed CR

• If continuing on study: Q6mo EMB until progression, D&C, or pt./provider decision

LIUD+Everolimus Arm

• If progression at cycle 3, 6, 9:

• Discontinue everolimus, patient taken off study

• CR at cycle 9:

• EMB to confirm response at cycle 12

• If response confirmed -EMB every 6 cycles (6 months)

• Continue evaluations on each cycle day 1

• SD at cycle 9:

• Discontinue everolimus, come off study ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Atypical Endometrial Hyperplasia
• Carcinoma, Endometrioid
• Endometrial Hyperplasia
• Endometrial Neoplasms
• FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
• FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma
• Hyperplasia

• NCT number: NCT02397083
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 23, 2015
• Completion date: September 30, 2026