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

Trial Summary

What is the purpose of this trial?

This trial tests if adding simvastatin to letrozole is better at stopping cancer cell growth in postmenopausal women with specific types of breast cancer. Letrozole lowers estrogen levels, and simvastatin may block enzymes that help cancer cells grow.

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.

What data supports the effectiveness of the drug Letrozole for breast cancer?

Research shows that Letrozole is more effective than Tamoxifen in improving disease-free survival and reducing the risk of breast cancer recurrence in postmenopausal women with hormone receptor-positive early breast cancer. ^{1 2 3 4 5}

Is the combination of Letrozole and Simvastatin safe for humans?

Letrozole is generally well tolerated in postmenopausal women with breast cancer, but it may increase the risk of bone fractures and heart issues compared to tamoxifen. Simvastatin is a commonly used medication to lower cholesterol and is generally considered safe, but specific safety data on the combination of Letrozole and Simvastatin is not available in the provided research. ^{5 6 7 8 9}

What makes the drug combination of Letrozole and Simvastatin unique for breast cancer treatment?

The combination of Letrozole, a drug that blocks estrogen production, and Simvastatin, typically used to lower cholesterol, is unique because it explores the potential added benefits of Simvastatin in enhancing the effectiveness of Letrozole for treating breast cancer, which is not a standard approach in current treatments. ^{1 5 6 10 11}

Research Team

Ruth L. Sacks, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

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

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

3. United States 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. [2018]

4. Netherlands 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. [2022]

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

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

6. 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]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? [2018]

10. Spain pubmed.ncbi.nlm.nih.gov

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

11. 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]