What is the mechanism of action of this treatment?

Aromatase inhibitors like Letrozole reduce estrogen levels by inhibiting the enzyme aromatase, which converts androgens into estrogens. This is particularly effective for estrogen receptor-positive breast cancer, as estrogen promotes cancer cell growth. Simvastatin, a statin, may block enzymes involved in cell growth, potentially enhancing Letrozole's effects. Understanding these mechanisms helps tailor treatments to target specific cancer pathways, improving outcomes and minimizing side effects for breast cancer patients.

What side effects are associated with this type of intervention?

Aromatase inhibitors, such as letrozole, commonly cause side effects including loss of bone density, increased risk of fractures, and cardiovascular issues. Patients may also experience joint pain, hot flashes, and fatigue. Simvastatin, used for enzyme blockade, can lead to muscle pain, liver enzyme abnormalities, and gastrointestinal symptoms. Combining these treatments may enhance the effectiveness against breast cancer but also requires careful monitoring for compounded side effects.

What prior FDA approvals exist?

Aromatase inhibitors, such as Letrozole, Anastrozole, and Exemestane, are FDA-approved for the treatment of hormone receptor-positive breast cancer in postmenopausal women. These drugs work by inhibiting the enzyme aromatase, which is involved in estrogen production. Letrozole, in particular, is used both as an adjuvant therapy and for advanced breast cancer. The combination of aromatase inhibitors with other agents, like the enzyme blockade approach being studied with Simvastatin, represents an ongoing area of research to enhance treatment efficacy.

What other types of research exist?

Promising novel alternatives to Letrozole with Simvastatin for breast cancer patients include: 1) CDK4/6 inhibitors (e.g., Palbociclib, Ribociclib, Abemaciclib) combined with aromatase inhibitors, which have shown significant improvement in progression-free survival. 2) PI3K inhibitors (e.g., Alpelisib) for patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative breast cancer. 3) mTOR inhibitors (e.g., Everolimus) combined with exemestane, which have demonstrated efficacy in hormone receptor-positive breast cancer. These alternatives offer different mechanisms of action and have been validated in clinical trials.

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Aromatase Inhibitor

Letrozole + Simvastatin for Breast Cancer

Phase < 1

Recruiting

Led By Ruth L Sacks

Research Sponsored by Emory University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 1 year

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include muscle pain, fatigue, nausea, increased liver enzymes which could indicate liver damage, and a risk of developing diabetes. Both drugs can also cause digestive issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Mean percentage change in Ki-67

Secondary study objectives

Regulatory T-Lymphocytes

Incidence of adverse events

Response per Ki-67

Other study objectives

Changes in HMG-CoA reductase immunohistochemistry (IHC) expression in the tumor tissue

Interleukin-6

Body Weight Changes

Side effects data

From 2018 Phase 4 trial • 79 Patients • NCT02137538

10%

Fracture

Acne

Scoliosis

Hair loss

Sacroiliitis

Neuro event

100%

80%

60%

40%

20%

Study treatment Arm

Anastrozole

Letrozole

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm I (letrozole, simvastatin)Experimental Treatment2 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 Control1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Simvastatin

2012

Completed Phase 4

~1270

Letrozole

2002

Completed Phase 4

~3590

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Aromatase inhibitors like Letrozole reduce estrogen levels by inhibiting the enzyme aromatase, which converts androgens into estrogens. This is particularly effective for estrogen receptor-positive breast cancer, as estrogen promotes cancer cell growth. Simvastatin, a statin, may block enzymes involved in cell growth, potentially enhancing Letrozole's effects. Understanding these mechanisms helps tailor treatments to target specific cancer pathways, improving outcomes and minimizing side effects for breast cancer patients.

KRAS-Mutated, Estrogen Receptor-Positive Low-Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery.Femara and the future: tailoring treatment and combination therapies with Femara.Importance of correlative science in advancing hormonal therapy and a new clinical paradigm for neoadjuvant therapy.