Levonorgestrel IUS + Everolimus for Endometrial Cancer

(LEVER Trial)

Recruiting at 23 trial locations

Overseen By Shannon Westin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Lipid lowering

Must not be taking: Corticosteroids, Immunosuppressive, others

Disqualifiers: Diabetes, Cardiac disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 9 months

102 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial requires a 28-day period without prior progesterone treatment before starting the study, unless you have tissue samples from before any progesterone treatment. If you are on medications that are contraindicated with everolimus, you must confirm with your doctor that you can change or stop them if you are assigned to the LIUD + everolimus group.

What data supports the effectiveness of the treatment Levonorgestrel IUS + Everolimus for Endometrial Cancer?

Research shows that the levonorgestrel-releasing intrauterine system (LNG-IUS) has been effective in treating early-stage endometrial cancer, especially when combined with other hormonal treatments, helping to preserve fertility in young women. ^{1 2 3 4 5}

Is the combination of Levonorgestrel IUS and Everolimus safe for treating endometrial cancer?

Everolimus, when taken orally, can have severe side effects that might require stopping or reducing the dose, but a new delivery system aims to reduce these side effects by targeting the drug directly to the uterus. The Levonorgestrel-releasing intrauterine system (LNG-IUS) has been used safely in various treatments, including preventing endometrial polyp recurrence and treating endometrial hyperplasia. ^{1 6 7 8 9}

How does the treatment Levonorgestrel IUS + Everolimus differ from other treatments for endometrial cancer?

The Levonorgestrel-Releasing Intrauterine System (LNG-IUS) is unique because it delivers medication directly to the uterus, which can help preserve fertility in women with endometrial cancer. This approach is particularly beneficial for those who are medically unfit for surgery or wish to maintain their ability to conceive. ^{3 4 10 11 12}

Research Team

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

Inclusion Criteria

You have enough infection-fighting white blood cells in your body.

Your platelet count is at least 100 billion per liter.

Your levels of ALT and AST in the blood should be less than 2.5 times the upper limit of normal.

Exclusion Criteria

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

You have been diagnosed with HIV.

I am not currently on cancer treatments or have had a break for at least 28 days or 7 days, depending on the treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the levonorgestrel-releasing intrauterine system alone or in combination with everolimus. Treatment is assessed every 3 months.

9 months

Visits every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with evaluations every 6 months if complete response is confirmed.

Up to 11 years

Treatment Details

Interventions

• Everolimus
• Levonorgestrel-Releasing Intrauterine System

Trial Overview 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.

Participant Groups

Group I: Arm II (LIUD, everolimus) Experimental Treatment 3 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 Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A new polymer-based intrauterine delivery system for everolimus allows for localized treatment of low-grade endometrial cancer, achieving effective drug levels similar to oral administration while minimizing systemic exposure.

In vivo studies in a rat model demonstrated that this delivery system can release everolimus for up to 84 days, effectively reducing cancer-related biomarkers and suggesting a promising non-surgical option for women wishing to preserve fertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications. Melendez, B., Shah, S., Jiang, Y., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparison of the effect of oral megestrol acetate with or without levonorgestrel-intrauterine system on fertility-preserving treatment in patients with early-stage endometrial cancer: a prospective, open-label, randomized controlled phase II trial (ClinicalTrials.gov NCT03241914). [2023]

2. England pubmed.ncbi.nlm.nih.gov

Fertility-Sparing Treatment of Early Endometrial Cancer and Complex Atypical Hyperplasia in Young Women of Childbearing Potential. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Conservative treatment with medroxyprogesterone acetate plus levonorgestrel intrauterine system for early-stage endometrial cancer in young women: pilot study. [2018]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Levonorgestrel-releasing intrauterine system-based therapies for early-stage endometrial cancer: a systematic review and meta-analysis. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Prevention of Benign Endometrial Polyp Recurrence Using a Levonorgestrel-releasing Intrauterine System in Premenopausal Patients: A Retrospective Cohort Study. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

LNG-IUS treatment of non-atypical endometrial hyperplasia in perimenopausal women: a randomized controlled trial. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Three-year follow-up of the use of a levonorgestrel-releasing intrauterine system in hormone replacement therapy. [2019]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and fertility outcomes of levonorgestrel-releasing intra-uterine system treatment for patients with atypical complex hyperplasia or endometrial cancer: a retrospective study. [2020]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Medically unfit women with early-stage endometrial cancer treated with the levonorgestrel intrauterine system. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women. [2013]