Letrozole + Simvastatin for Breast Cancer

Recruiting at 3 trial locations

Overseen By Ruth L. Sacks, MD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Emory University

Must be taking: Letrozole

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Active infection, Cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding simvastatin, a cholesterol-lowering medication, to letrozole, a hormone therapy, can more effectively stop the growth of breast cancer cells compared to letrozole alone. It targets patients with stage I-III hormone receptor-positive, HER2-negative invasive breast cancer. Participants will receive either both letrozole and simvastatin or just letrozole to compare outcomes. Ideal participants are post-menopausal women with a confirmed diagnosis of this type of breast cancer. As an Early Phase 1 trial, this research aims to understand how the combination treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial requires that you stop taking statins, fibrates, or ezetimibe at least 3 months before enrolling. Additionally, you cannot use strong CYP3A4 inhibitors or certain other medications during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that letrozole is generally a well-tolerated treatment for breast cancer. It is often used for postmenopausal women with a type of early breast cancer that responds to hormones, with 76.8% of patients experiencing good results without major side effects.

Studies suggest that combining simvastatin with letrozole might help stop cancer cells from growing. Statins like simvastatin are also known to lower the risk of breast cancer returning. They can slow down cancer cell growth and may even help destroy them.

Although this trial is in its early stages, both letrozole and simvastatin have shown safety in humans. Letrozole already has FDA approval for treating breast cancer, providing reassurance about its safety. The combination with simvastatin appears promising in research but is still under study to ensure safety and effectiveness in this specific use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of letrozole and simvastatin for breast cancer treatment because it offers a potentially enhanced approach to inhibiting cancer growth. Letrozole is an aromatase inhibitor, commonly used to lower estrogen levels and slow cancer progression in hormone receptor-positive breast cancer. The addition of simvastatin, typically used for lowering cholesterol, is thought to have anti-cancer properties by interfering with cancer cell growth and survival. This novel combination could improve treatment outcomes by attacking cancer cells through different biological pathways simultaneously.

What evidence suggests that letrozole with simvastatin might be an effective treatment for breast cancer?

Research has shown that letrozole effectively treats hormone receptor-positive breast cancer, with about 76.8% of patients responding positively. In this trial, some participants will receive letrozole alone, while others will receive a combination of letrozole and simvastatin. Studies suggest that adding simvastatin to letrozole might improve outcomes by slowing cancer growth and reducing recurrence. Statins, such as simvastatin, are known to slow cancer cell growth and help kill cancer cells. This combination could more effectively stop tumor growth than letrozole alone. ^{1 2 3 4 5}

Who Is on the Research Team?

Ruth L. Sacks, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for post-menopausal women aged 18 or older with stage I-III hormone receptor positive, HER2 negative invasive breast cancer. Participants must not have had systemic therapy, statins, or certain cholesterol medications in the last 3 months and should have no active liver disease. They need normal blood counts and organ function tests.

Inclusion Criteria

Platelets >= 100,000/mcL

Total bilirubin =< 2 institutional upper limit of normal

Hemoglobin >= 9.0 g/dl

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

History of allergic reactions to compounds of similar composition to simvastatin and/or letrozole

I am not taking strong CYP3A4 inhibitors, cyclosporine, danazol, or gemfibrozil.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive letrozole with or without simvastatin for 14 days

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole
• Simvastatin

Trial Overview The study is testing if combining Letrozole with Simvastatin improves treatment outcomes compared to using Letrozole alone in stopping tumor growth. It's an early phase I trial where one group receives both drugs while another only gets Letrozole.

How Is the Trial Designed?

Group I: Arm I (letrozole, simvastatin) Experimental Treatment 2 Interventions

Patients receive letrozole PO QD and simvastatin PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (letrozole) Active Control 1 Intervention

Patients receive letrozole PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 of 150 breast cancer patients, those receiving sequential treatment with letrozole and tamoxifen showed a higher overall response rate and fewer adverse reactions compared to those on letrozole alone.

Both treatment methods resulted in similar survival rates, but the sequential therapy group had a significantly lower recurrence rate and better improvement in blood lipid levels, indicating a potentially better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. Lu, X., Qian, C.[2023]

In a study comparing letrozole and tamoxifen for 5 years in postmenopausal women with hormone receptor-positive early breast cancer, letrozole significantly improved disease-free survival by 19% and reduced the risk of breast cancer recurrence by 28%.

Letrozole is considered cost-effective, yielding an additional 0.409 quality-adjusted life years (QALYs) at an additional cost of $9705 compared to tamoxifen, resulting in a cost per QALY gained of $23,743.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer. Delea, TE., Karnon, J., Sofrygin, O., et al.[2018]

In a randomized trial, letrozole significantly improved disease-free survival by 19% and reduced the risk of breast cancer recurrence by 28% compared to tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer.

Letrozole is considered cost-effective, providing an additional 0.343 quality-adjusted life years (QALYs) at an incremental cost of Can$ 8,110, resulting in a cost per QALY gained of Can$ 23,662 from the Canadian healthcare perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in postmenopausal women with hormone-receptor positive early breast cancer from a Canadian perspective. Delea, TE., El-Ouagari, K., Karnon, J., et al.[2022]

In a study of 907 postmenopausal women with advanced breast cancer, letrozole was found to be more effective than tamoxifen, showing a longer time to progression (TTP) in both younger (<70 years) and older (≥70 years) patients.

Letrozole also demonstrated a significantly higher objective response rate (ORR) in older patients (38% vs. 18% for tamoxifen), while the ORR in younger patients was similar for both treatments (26% for letrozole vs. 22% for tamoxifen).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer. Mouridsen, H., Chaudri-Ross, HA.[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]

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 significantly improves disease-free survival (DFS) and reduces distant recurrences in postmenopausal women with early breast cancer compared to tamoxifen, based on a study involving 8,010 participants over 25.8 months.

While letrozole is associated with fewer venous thromboembolic and endometrial events than tamoxifen, it does have a slightly higher incidence of skeletal and serious cardiac events, though these are relatively low overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of early adjuvant aromatase inhibitor therapy: contributions from the BIG 1-98 letrozole trial. Forbes, JF.[2018]

In a study of 1065 postmenopausal women with early breast cancer receiving letrozole, immediate treatment with zoledronic acid significantly increased lumbar spine bone mineral density (BMD) by 5.7% compared to a delayed treatment strategy, which resulted in bone loss.

Both immediate and delayed zoledronic acid regimens were well tolerated, but the immediate group experienced more bone pain due to acute-phase reactions, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Bundred, NJ., Campbell, ID., Davidson, N., et al.[2022]

The FACE trial is a large-scale study involving 4000 postmenopausal women with hormone receptor-positive, node-positive breast cancer, comparing the efficacy and safety of letrozole and anastrozole over a treatment period of up to 5 years.

The primary goal of the trial is to assess disease-free survival (DFS), while secondary objectives include evaluating overall survival (OS) and the time to distant metastases, which will provide comprehensive insights into the effectiveness of both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? Jonat, W., Mundhenke, C.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7376511/

Statin use and breast cancer recurrence in ... Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05464810

Letrozole With and Without Simvastatin for the Treatment of ... The addition of simvastatin to letrozole may be more effective at stopping the growth of cancer cells than letrozole alone.

3. secioj.journals.ekb.eg secioj.journals.ekb.eg/article_424408_ebb65d530bf9fa38699866ff9adce871.pdf

Letrozole plus Simvastatin versus ... cancer showed a significant reduction in breast cancer recurrence. Objective: We evaluated the role of simvastatin in combination with letrozole in denovo ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33797

Association of statin use with clinical outcomes in patients with ... It has been demonstrated that statins decrease breast cancer cell proliferation while increasing apoptosis, target key TNBC-associated pathways, ...

5. withpower.com withpower.com/trial/early-phase-1-carcinoma-7-2022-3eada

Letrozole + Simvastatin for Breast Cancer 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 ...