Letrozole for Uterine Fibroids

(PLUM Trial)

Recruiting at 2 trial locations

Overseen By Study Coordinator

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Aromatase inhibitors, SERMs, Estrogens, Methadone

Disqualifiers: Pregnancy, Breast cancer, Osteoporosis, others

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: 12 weeks

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests letrozole, a medication, to determine its effectiveness in alleviating symptoms of uterine fibroids, such as heavy bleeding and pelvic discomfort. Participants will receive either letrozole or a placebo (a pill with no active ingredients) to compare effects. Women who have experienced these symptoms and have had their fibroids confirmed by ultrasound or MRI in the last two years may be suitable for this study. The goal is to enhance the quality of life for those dealing with fibroid symptoms. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients, offering a chance to contribute to broader knowledge while potentially improving symptoms.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as letrozole, other aromatase inhibitors, selective estrogen receptor modulators (SERMs), and certain hormone therapies, at least 4 weeks before starting the study. Additionally, you should not use medications that might interact unsafely with letrozole, like methadone or thalidomide, in the 4 weeks before the trial.

What is the safety track record for letrozole?

Research has shown that letrozole is usually well-tolerated in treating uterine fibroids. Studies have found that letrozole can significantly shrink uterine fibroids and alleviate symptoms like heavy menstrual bleeding. These studies also indicate that letrozole has been used safely for up to three months.

Since this trial is in a later stage, good evidence already exists regarding the safety of letrozole for this condition. Additionally, letrozole is an FDA-approved medication for other uses, which enhances its safety reputation. However, like any medication, side effects may occur, so discussing these with the study team or a doctor is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Letrozole is unique because it targets uterine fibroids by reducing estrogen levels, which is different from the standard treatments like GnRH agonists or surgical options that either temporarily shrink fibroids or remove them. Unlike these conventional methods, Letrozole is an oral medication that offers a non-invasive approach, providing convenience and potentially fewer side effects. Researchers are excited about Letrozole because its mechanism of inhibiting aromatase, an enzyme involved in estrogen production, presents a promising alternative that could lead to effective fibroid management without surgery.

What is the effectiveness track record for letrozole in treating uterine fibroids?

Research has shown that letrozole, which participants in this trial may receive, can help shrink uterine fibroids. Studies have found that letrozole can reduce fibroid size by 35-55% within 8-12 weeks. One study reported a 46% reduction in fibroid size after 12 weeks of use. Women taking letrozole also experienced relief from heavy menstrual bleeding caused by fibroids. This suggests that letrozole can significantly improve symptoms and quality of life for those with uterine fibroids. ^{1 2 4 6 7}

Who Is on the Research Team?

Vanessa Jacoby, MD, MAS

Principal Investigator

University of California, San Francisco

Alison Huang, MD, MAS, MPhil

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 21-54 who have confirmed uterine fibroids with symptoms like heavy bleeding, pelvic discomfort, or urinary issues. Participants must have regular menstrual cycles and agree to use non-hormonal contraception if sexually active.

Inclusion Criteria

If you are at risk of getting pregnant, you agree to use a non-hormonal barrier method of birth control during the study.

I experience heavy bleeding, pelvic discomfort, or pain during sex due to fibroids.

My menstrual cycles are regular, lasting 21 to 38 days and no longer than 14 days for the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral letrozole 2.5mg/day or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole

Trial Overview The PLUM Study is testing the effectiveness of Letrozole (2.5mg) compared to a placebo in reducing symptoms related to uterine fibroids and improving quality of life, as well as decreasing the size of leiomyoma and the uterus itself.

How Is the Trial Designed?

Group I: Letrozole Experimental Treatment 1 Intervention

Oral letrozole 2.5mg/day

Group II: Placebo and Letrozole Placebo Group 2 Interventions

Placebo capsule for 12 weeks; Oral letrozole 2.5mg/day for 12 weeks

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?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[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]

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 study of 39 patients undergoing HIFU ablation for uterine fibroids, letrozole pretreatment showed improved energy and treatment efficiency compared to no medication and GnRHa, particularly for larger fibroids over 10 cm.

While GnRHa resulted in a greater volume reduction of fibroids (38.6% vs. 16.4% for letrozole), it also led to more hypoestrogenic symptoms and longer treatment times, suggesting letrozole may be a safer and more efficient option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole as premedication of high intensity focused ultrasound treatment of uterine fibroids: A retrospective observation study. Chen, WC., Hsu, CC., Huang, HJ., et al.[2022]

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, an aromatase inhibitor, was effective in treating endometrial hyperplasia in a small case series of five premenopausal women, with no evidence of hyperplasia or atypia after 3 months of treatment.

All patients showed low serum levels of estradiol, suggesting that letrozole effectively reduces estrogen levels, which may contribute to its therapeutic action; however, further studies are necessary to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole as primary therapy for endometrial hyperplasia in young women. Li, HZ., Chen, XN., Qiao, J.[2018]

In a study involving BALB/c female mice, letrozole (Ltz) did not demonstrate antiestrogenic effects in preventing endometrial hyperplasia induced by carcinogen and estrogen, as both Ltz and estrogen treatments resulted in higher incidences of hyperplasia compared to the control group.

The combination of medroxyprogesterone acetate (MPA) showed a protective effect against endometrial hyperplasia, indicating that Ltz may not be effective in this context, as it did not reduce the severity of lesions compared to MPA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice. Lara, AC., Cândido, EB., Vidigal, PV., 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]

Letrozole, a non-steroidal aromatase inhibitor, significantly reduced the size of uterine leiomyomas in 16 premenopausal women over a 3-month treatment period, improving symptoms like heavy menstrual bleeding.

The treatment did not negatively impact bone mineral density, suggesting that letrozole may be a safe option for managing uterine leiomyomas, although further research with larger trials is necessary to confirm its overall safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of symptomatic uterine leiomyoma with letrozole. Gurates, B., Parmaksiz, C., Kilic, G., et al.[2022]

Letrozole and anastrozole significantly increased apoptosis in epithelial endometrial cells from patients with endometriosis, particularly at higher concentrations (10 nM for Letrozole and 100-500 nM for Anastrozole).

Both drugs also reduced cell proliferation in these cells, indicating their potential as effective treatments for endometriosis by promoting cell death and inhibiting growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis. Meresman, GF., Bilotas, M., Abello, V., et al.[2006]

Citations

1. database.clin-star.org database.clin-star.org/display/project-5R01HD11246502

Letrozole for Treatment of Uterine Fibroids: A randomized ... In a few small uncontrolled studies, fibroid volume decreased 35-55% during 8-12 weeks of treatment. We recently completed a pilot, randomized, placebo- ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1472648310602465

Treatment of symptomatic uterine leiomyoma with letrozole Letrozole significantly decreased uterine leiomyoma sizes (P < 0.01) and promptly benefited women with heavy menstrual bleeding associated with leiomyomas ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11366412/

Aromatase inhibitors for uterine fibroids - PMC - PubMed Central Use of letrozole reduced fibroid volume by 46% and use of a gonadotrophin‐releasing hormone (GnRH) agonist (GnRHa) by 32% after 12 weeks of treatment; these ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/41/NCT02470741/Prot_SAP_000.pdf

1 The PLUM Study: Pilot of Letrozole for Uterine Myomas PI The PLUM study will also provide preliminary data on the efficacy of letrozole in treating uterine fibroids. We will use PLUM outcome data to estimate effect ...

5. 2024.sci-hub.box 2024.sci-hub.box/2026/bee6d3737ca80d38837c0ddf285d4ff6/gurates2008.pdf

Treatment of symptomatic uterine leiomyoma with letrozole Letrozole resulted in a significant decrease of leiomyoma size at the end of the first treatment cycle (P < 0.01), therefore suggesting an immediate effect of ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06143631

Prescription of Letrozole for Uterine Myoma A randomized, double-blinded, 2-arm, parallel-group, placebo-controlled trial is designed to compare the efficacy of letrozole versus placebo on leiomyoma- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9763453/

Letrozole as premedication of high intensity focused ... Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma.