Letrozole for Leiomyosarcoma
Recruiting in Palo Alto (17 mi)
+11 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: GOG Foundation
Must not be taking: Aromatase inhibitors, Systemic estrogens
Disqualifiers: Mixed tumors, Severe diseases, Others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
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.
12345Is 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.
13678How 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.
123910Eligibility 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.
+4 more
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.
+8 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: LetrozoleExperimental Treatment1 Intervention
Letrozole 2.5 mg orally
Group II: ObservationActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Women's Cancer Center of NevadaLas Vegas, NV
Endeavor Health - Kellogg Cancer CenterEvanston, IL
University of Massachusetts Memorial Medical CenterWorcester, MA
University of New Mexico Comprehensive Cancer CenterAlbuquerque, NM
More Trial Locations
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Who Is Running the Clinical Trial?
GOG FoundationLead Sponsor
References
A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS). [2022]Up to 87% of uterine leiomyosarcomas have estrogen receptor positivity. There are no effective adjuvant therapies for LMS. The objective of this study was to determine the efficacy of letrozole in patients with newly diagnosed uterine leiomyosarcoma (uLMS). The primary endpoint of this study was a reduction in the recurrence rate for patients with this disease.
Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. [2021]Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.
Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum. [2018]To evaluate the efficacy and safety of letrozole in patients with recurrent platinum- and taxane-resistant estrogen receptor-positive (ER+) high-grade cancer of the ovary or peritoneum.
Letrozole as primary medical therapy for locally advanced and large operable breast cancer. [2022]To investigate the efficacy of letrozole 2.5 mg and 10 mg used as primary neoadjuvant therapy for patients with locally advanced and large operable breast cancer.
Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer. [2022]Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy (PST) in postmenopausal women with ER-positive early breast cancer. However, the optimum duration of endocrine PST remains uncertain.
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]Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) -positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.
Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. [2021]On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.
Letrozole: advancing hormone therapy in breast cancer. [2018]Letrozole is a type 2 aromatase inhibitor, which reduces availability of estrogen in postmenopausal women, thereby decreasing its ability to stimulate breast cancer cells. Phase III trials in both the advanced and early breast cancer setting have shown an improvement in disease-free survival compared with other compounds, including tamoxifen. Letrozole is well-tolerated, with the main adverse effects reported as hot flushes, arthritis, arthralgia and myalgia, and a trend towards increased risk of fracture.
The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review. [2019]Letrozole is a third-generation aromatase inhibitor for use in postmenopausal women with hormonal-sensitive breast cancer. This drug was found to reduce or effectively shrink tumors in a significant number of such patients. It exhibits antitumor activity at a relatively low daily dose, and is highly potent and selective and well tolerated. Results from recent phase III clinical studies have confirmed the efficacy and the key role of this drug in the therapy of advanced breast cancer in postmenopausal women. Moreover, letrozole demonstrated higher activity and lower toxicity compared to tamoxifen in the first-line therapy of postmenopausal women affected with advanced breast cancer. However, it also represents a valid option in second-line therapy after tamoxifen failure. New data on this agent in adjuvant or neoadjuvant treatment also suggest efficacy in the treatment of early breast cancer. This article reviews the clinical data on letrozole in all settings and its future potential in chemoprevention. (c) 2001 Prous Science. All rights reserved.
Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review. [2023]Endometrial stromal sarcomas are rare tumors that recur long after initial excision. We report a case of recurrent endometrial stromal sarcoma treated with the aromatase inhibitor letrozole and an overview of research completed to date. A 59-year-old female presented with new abdominal onset pain, fatigue, and nausea. She had a computed tomography that showed a pelvic mass, an enlarged right internal iliac lymph node, an atypical liver hemangioma, and a severe left hydronephrosis. The patient underwent an exploratory laparotomy, and attempted surgical resection of the pelvic mass was attempted. Pathology was consistent with recurrent endometrial stromal sarcoma. Since these tumors are hormonally sensitive, the patient was started on letrozole 2.5 mg daily. The patient had complete clinical and radiographic response by 11 months. After 24 months of therapy, the patient remained free of disease. Endometrial stromal sarcomas are hormonally sensitive tumors. Progestins function to decrease the effects of estrogen on target cells and have been used for primary therapy of endometrial stromal sarcomas. Aromatase inhibitors block peripheral synthesis of estrogen. Letrozole is a type 2 aromatase inhibitor that effectively reduces serum estrogen levels. Letrozole has been described as treatment for endometrial stromal sarcoma. Letrozole is well tolerated and is a good option for long-term management of this disease.