What side effects are associated with this type of intervention?

The Levonorgestrel-Releasing Intrauterine System (LNG IUS) is generally well-tolerated but can cause side effects such as irregular bleeding, headaches, breast tenderness, and mood changes. Rarely, it may lead to uterine perforation or infection. Everolimus, an mTOR inhibitor, can cause serious side effects including pneumonitis, mucositis, fatigue, gastrointestinal issues, and pain. It may also lead to immunosuppression, increasing the risk of infections. Both treatments aim to manage endometrial hyperplasia by hormonal regulation and inhibition of cell growth, respectively.

What prior FDA approvals exist?

The FDA has approved the Levonorgestrel-Releasing Intrauterine System (LNG-IUS) for the treatment of Endometrial Hyperplasia. This system releases levonorgestrel, a type of progesterone, which helps in preventing pregnancy and may slow the growth of tumor cells. Everolimus, an mTOR inhibitor, is used to block enzymes necessary for cell growth, although its primary approvals are for other types of cancers. These treatments align with the mechanisms being studied in the trial involving the Levonorgestrel-Releasing Intrauterine System and Everolimus for treating Endometrial Hyperplasia.

What other types of research exist?

Promising novel alternatives for treating Endometrial Hyperplasia in 2024 include selective progesterone receptor modulators (SPRMs) like ulipristal acetate, which has shown efficacy in reducing fibroid-related bleeding and improving quality of life. Additionally, aromatase inhibitors such as letrozole may offer benefits by reducing estrogen production, which can help manage hyperplasia. Another potential alternative is the use of CDK inhibitors like roscovitine, which have shown promise in preclinical studies for slowing disease progression. These alternatives should be discussed with a healthcare provider to determine the best individualized treatment plan.

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Hormone Therapy

Levonorgestrel IUS + Everolimus for Endometrial Cancer (LEVER Trial)

Q: What is the mechanism of action of this treatment?

The Levonorgestrel-Releasing Intrauterine System (LNG-IUS) releases levonorgestrel, a type of progesterone, which thins the endometrial lining and reduces hyperplasia by counteracting estrogen's effects, thus preventing progression to endometrial cancer. Everolimus, an mTOR inhibitor, blocks enzymes needed for cell growth and proliferation, potentially slowing the growth of hyperplastic or cancerous cells. These mechanisms are crucial for patients as they help manage the condition and reduce the risk of progression to more severe disease.

Phase 2

Waitlist Available

Led By Shannon N Westin

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

International normalized ratio (INR) =< 2; factor 10A drawn if patient on anticoagulant Eliquis

Must not have

Other malignancies within the past 3 years except for basal or squamous cell carcinoma of the skin

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 11 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a hormone-releasing device inside the uterus, alone or with a drug called everolimus, for patients with pre-cancerous growths or early-stage uterine cancer. The device releases a hormone to control cell growth, while everolimus helps stop cancer cells from growing. Everolimus has shown promising results for various types of cancer, including breast cancer.

Who is the study for?

This trial is for patients with atypical hyperplasia or stage IA grade 1 endometrial cancer. Eligible participants must have proper liver function, not be pregnant or nursing, and cannot have HIV or other recent malignancies. They should not be on certain medications that can't be combined with everolimus and must agree to use additional contraception if of childbearing potential.

What is being tested?

The study is testing the effectiveness of a levonorgestrel-releasing intrauterine device (LIUD), alone or with the drug everolimus, in preventing tumor growth in patients with early-stage endometrial cancer or pre-cancerous uterine growths. It's unclear if adding everolimus improves outcomes compared to LIUD alone.

What are the potential side effects?

Possible side effects include hormone-related changes from the LIUD and reactions to everolimus such as immune system suppression, increased risk of infections, mouth ulcers, skin issues, high blood sugar levels, non-serious bleeding disorders, and potentially impaired lung function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of my waking hours.

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My blood clotting time is normal or near normal.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had cancer in the last 3 years, except for skin cancer.

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My uterine cancer is of a specific type and severity.

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I do not have severe heart, liver, lung problems, infections that antibiotics can't treat, or a bleeding disorder.

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My cancer has spread beyond the uterus, confirmed by imaging or surgery.

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I have been diagnosed with genital actinomycosis.

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I do not have any severe infections that are uncontrolled or not responding to treatment.

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I am allergic to everolimus or similar medications.

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I am not pregnant or nursing.

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I have previously been treated with everolimus or similar drugs.

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I have a birth defect or condition that changes the shape of my uterus.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 11 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 11 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 11 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Response rate (levonorgestrel intrauterine device [LIUD] alone)

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)

Secondary study objectives

Incidence of adverse events

Overall survival

Progression free survival

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (LIUD, everolimus)Experimental Treatment3 Interventions

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.

Group II: Arm I (LIUD)Experimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Everolimus

2010

Completed Phase 4

~1510

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The Levonorgestrel-Releasing Intrauterine System (LNG-IUS) releases levonorgestrel, a type of progesterone, which thins the endometrial lining and reduces hyperplasia by counteracting estrogen's effects, thus preventing progression to endometrial cancer. Everolimus, an mTOR inhibitor, blocks enzymes needed for cell growth and proliferation, potentially slowing the growth of hyperplastic or cancerous cells. These mechanisms are crucial for patients as they help manage the condition and reduce the risk of progression to more severe disease.