Letrozole for Leiomyosarcoma

Recruiting at 11 trial locations

Overseen By Jennifer Klein, MEd

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: GOG Foundation

Must not be taking: Aromatase inhibitors, Systemic estrogens

Disqualifiers: Mixed tumors, Severe diseases, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until progression

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether letrozole can stop the progression of uterine leiomyosarcoma, a cancer originating in the muscle layer of the uterus. The goal is to determine if daily letrozole intake can extend the time patients live without cancer worsening. The trial seeks participants diagnosed with uterine leiomyosarcoma confined to the uterus, who have completed surgery to remove the uterus and ovaries, and show no signs of disease spread. Participants must also have tumors with high estrogen receptor levels, indicating potential responsiveness to hormone treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop using systemic estrogens, including herbals and supplements with estrogenic properties, but vaginal estrogen is allowed if needed. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that letrozole is likely to be safe for humans?

Research has shown that letrozole is safe and generally well-tolerated by patients. Studies have reported no major safety issues with letrozole. Patients taking it often experience a high progression-free rate, meaning their condition does not worsen over time. This suggests that letrozole is effective and does not cause significant harm.

Some patients might experience mild side effects, but the body usually handles this medication well. Letrozole is already FDA-approved for other uses, indicating its safety. It is important to consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leiomyosarcoma?

Letrozole is unique for treating leiomyosarcoma because it targets the estrogen receptor pathway, which isn't typically the focus of standard treatments like surgery, chemotherapy, or radiation. Unlike these more aggressive treatments, letrozole is an oral aromatase inhibitor that reduces estrogen levels, potentially slowing the growth of estrogen-dependent tumors. Researchers are excited about letrozole because it offers a less invasive option that might work effectively against hormone-sensitive cancers, providing new hope for patients with this challenging condition.

What evidence suggests that letrozole might be an effective treatment for uterine leiomyosarcoma?

Research has shown that letrozole may help treat certain cancers, such as breast cancer, by blocking estrogen, a hormone that some cancers need to grow. This is significant because many uterine leiomyosarcomas also depend on estrogen. One study found that letrozole was effective for 11 out of 37 patients, with no disease progression after 12 weeks. In this trial, participants will either receive letrozole or be placed under observation to determine if letrozole can improve outcomes for those newly diagnosed with uterine leiomyosarcoma. These findings suggest that letrozole might help slow the disease by targeting its reliance on hormones. ^{1 2 3 4 6}

Who Is on the Research Team?

Bradley Corr, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for patients with a specific cancer of the uterus called leiomyosarcoma, limited to early stages (1 or 2). Participants must have had surgery to remove their uterus and ovaries recently, show estrogen receptor positivity in tumor cells, be able to take pills orally, and have good overall health and organ function. They should not have any measurable disease left.

Inclusion Criteria

I can swallow pills.

My tumor is ER positive, with at least 10% cells showing ER positivity.

I had surgery to remove my uterus and both ovaries within the last 12 weeks.

Exclusion Criteria

Patients who are pregnant or breast-feeding

Patients deemed otherwise clinically unfit for clinical trial per investigators discretion

My cancer is not a mixed type but a pure uterine sarcoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2.5 mg of letrozole orally daily

Until progression

Observation

Participants are monitored without active treatment

Until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole

Trial Overview The trial is testing if letrozole at doses of 2/5 mg daily can extend the time patients live without their cancer getting worse. Letrozole is a hormone therapy that lowers estrogen levels which may help slow the growth of certain cancers.

How Is the Trial Designed?

Group I: Letrozole Experimental Treatment 1 Intervention

Letrozole 2.5 mg orally

Group II: Observation Active Control 1 Intervention

Observation

Letrozole is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Who Is Running the Clinical Trial?

GOG Foundation

Lead Sponsor

Trials

48

Recruited

18,500+

Published Research Related to This Trial

Letrozole is an effective aromatase inhibitor for postmenopausal women with hormone-sensitive breast cancer, showing significant tumor reduction and well-tolerated at low daily doses, as confirmed by recent phase III clinical studies.

It has demonstrated superior efficacy and lower toxicity compared to tamoxifen in first-line therapy for advanced breast cancer, and is also a viable option for second-line treatment after tamoxifen failure, with potential benefits in early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review. Crucitta, E., Locopo, N., Silvestris, N., et al.[2019]

Letrozole, a type 2 aromatase inhibitor, effectively reduces estrogen levels in postmenopausal women, leading to improved disease-free survival in breast cancer patients compared to other treatments like tamoxifen.

The drug is generally well-tolerated, though it may cause side effects such as hot flushes, joint pain, and a potential increased risk of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: advancing hormone therapy in breast cancer. Lee, RJ., Armstrong, AC., Wardley, AM.[2018]

In a phase II study involving 33 women with recurrent estrogen receptor-positive ovarian cancer, letrozole showed a clinical benefit in 26% of patients, with one achieving a partial response and seven having stable disease.

Letrozole was well-tolerated, with no severe toxicities reported, and the most common side effects were mild, such as fatigue and sweating, indicating a favorable safety profile for this treatment in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum. Ramirez, PT., Schmeler, KM., Milam, MR., et al.[2018]

Letrozole has been fully approved by the FDA for treating postmenopausal women with hormone receptor-positive early breast cancer, showing a significant improvement in disease-free survival compared to tamoxifen, with a hazard ratio of 0.87 in the adjuvant trial.

While letrozole is effective, it is associated with a higher risk of bone fractures and myocardial infarction compared to tamoxifen, which has its own risks such as endometrial cancer and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. Cohen, MH., Johnson, JR., Justice, R., et al.[2021]

A 59-year-old woman with recurrent endometrial stromal sarcoma showed a complete clinical and radiographic response after 11 months of treatment with the aromatase inhibitor letrozole, and remained disease-free after 24 months.

Letrozole, which effectively reduces estrogen levels, is well tolerated and serves as a promising long-term management option for hormonally sensitive endometrial stromal sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review. Sylvestre, VT., Dunton, CJ.[2023]

In a study involving 4,136 postmenopausal women with hormone receptor-positive, node-positive early breast cancer, letrozole showed a 5-year disease-free survival rate of 84.9%, compared to 82.9% for anastrozole, indicating no significant difference in efficacy between the two treatments.

Both letrozole and anastrozole had similar safety profiles, with the most common adverse events being arthralgia and hypertension, suggesting that either medication can be safely used in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial. Smith, I., Yardley, D., Burris, H., et al.[2022]

Letrozole is highly effective and well-tolerated as a neoadjuvant therapy for postmenopausal women with ER-positive early breast cancer, with 76.8% of patients showing an objective response.

The study suggests that an optimal treatment duration of 4 to 6 months is sufficient to achieve maximum response, with modest benefits observed if treatment is extended beyond this period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer. Llombart-Cussac, A., Guerrero, Á., Galán, A., et al.[2022]

Letrozole is more effective than tamoxifen for adjuvant therapy in postmenopausal women with hormone-responsive early breast cancer, and it is well tolerated by patients.

Extended therapy with letrozole after tamoxifen treatment is more effective than placebo, making it a valuable treatment option while ongoing trials investigate the best duration and comparison with other aromatase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. Keating, GM.[2021]

In a small randomized phase II study involving 9 patients with newly diagnosed uterine leiomyosarcoma, letrozole showed promising results, with a median progression-free survival (PFS) not reached compared to 17.3 months in the observation group.

Patients receiving letrozole had a 100% progression-free rate at 12 months and maintained a significant advantage over the observation group, suggesting that letrozole may be a potential adjuvant therapy for early-stage uLMS, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS). Slomovitz, BM., Taub, MC., Huang, M., et al.[2022]

Letrozole, at both 2.5 mg and 10 mg doses, was effective as a neoadjuvant therapy for locally advanced breast cancer, with significant reductions in tumor volume observed in all patients, allowing for breast-conserving surgery.

There were no significant differences in efficacy between the two doses, and both were well-tolerated with no recordable side effects, indicating a favorable safety profile for letrozole in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Dixon, JM., Love, CD., Bellamy, CO., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6260388/

A randomized phase II study of letrozole vs. observation in ... The objective of this study was to determine the efficacy of letrozole in patients with newly diagnosed uterine leiomyosarcoma (uLMS).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05649956

NCT05649956 | Letrozole in Uterine Leiomyosarcoma This is a randomized phase II study of letrozole (Femara) administered 2.5 mg orally daily to patients with newly diagnosed clinical stage I and II LMS.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5643

GOG 3088: A randomized phase II study of letrozole versus ... This is a GOG Foundation led phase II randomized controlled trial comparing letrozole (2.5mg PO daily) to observation in newly diagnosed patients with uterine ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.28476

Phase 2 trial of aromatase inhibition with letrozole in patients ... If ≥ 11 patients among 37 eligible patients were free of disease progression at 12 weeks, letrozole was to be considered effective and worthy ...

5. withpower.com withpower.com/trial/phase-2-leiomyosarcoma-3-2023-8013e

Letrozole for Leiomyosarcoma · Recruiting Participants for ... Letrozole has shown effectiveness in treating hormone-responsive cancers, such as breast cancer, by blocking estrogen, which many leiomyosarcomas also rely on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5224847/

Survival of patients with metastatic leiomyosarcoma We reviewed patients' demographics, medical history, clinical characteristics, laboratory results, gene aberrations, and status of phase I trial therapy. Trial ...