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

Trial Summary

What is the purpose of this trial?

This is a clinical trial to test letrozole in patients with uterine leiomyosarcoma. The main question is will treatment with letrozole extend progression-free survival in patients. Patients will receive 2/5 mg of letrozole daily.

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.

What data supports the effectiveness of the drug Letrozole for treating leiomyosarcoma?

Letrozole has shown effectiveness in treating hormone-responsive cancers, such as breast cancer, by blocking estrogen, which many leiomyosarcomas also rely on to grow. A study specifically on uterine leiomyosarcoma aimed to see if letrozole could reduce the recurrence of this cancer, suggesting potential benefits. ^{1 2 3 4 5}

Is letrozole generally safe for humans?

Letrozole is generally well-tolerated in humans, with common side effects including hot flushes (sudden feelings of warmth), joint pain, and muscle pain. There is also a trend towards an increased risk of bone fractures and heart issues, such as myocardial infarction (heart attack), compared to some other treatments. ^{1 3 6 7 8}

How is the drug letrozole unique in treating leiomyosarcoma?

Letrozole is unique in treating leiomyosarcoma because it targets estrogen receptor-positive tumors by reducing estrogen levels, which is important since up to 87% of uterine leiomyosarcomas have estrogen receptor positivity. This approach is novel as there are currently no effective adjuvant therapies for leiomyosarcoma. ^{1 2 3 9 10}

Research Team

Bradley Corr, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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, 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]

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]

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 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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS). [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Letrozole as primary medical therapy for locally advanced and large operable breast cancer. [2022]

5. Italy 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. [2022]

6. United States 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. [2022]

7. England 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. [2021]

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

Letrozole: advancing hormone therapy in breast cancer. [2018]

9. Spain pubmed.ncbi.nlm.nih.gov

The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review. [2019]

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

Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review. [2023]