Recruiting

Early Phase 1

Letrozole with SimvastatinLetrozole With and Without Simvastatin for the Treatment of Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer

Sponsor:

Emory University

Code:

NCT05464810

Conditions

Anatomic Stage I Breast Cancer AJCC v8

Anatomic Stage II Breast Cancer AJCC v8

Anatomic Stage III Breast Cancer AJCC v8

HER2-Negative Breast Carcinoma

Hormone Receptor-Positive Breast Carcinoma

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Letrozole

Simvastatin

Study Details

Brief summary:

This early phase I trial tests whether letrozole with simvastatin works better than letrozole alone to stop tumor cell proliferation in patients with stage I-III hormone receptor positive, HER2 negative invasive breast cancer. Letrozole and simvastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. The addition of simvastatin to letrozole may be more effective at stopping the growth of cancer cells than letrozole alone.

Conditions

Anatomic Stage I Breast Cancer AJCC v8

Anatomic Stage II Breast Cancer AJCC v8

Anatomic Stage III Breast Cancer AJCC v8

HER2-Negative Breast Carcinoma

Hormone Receptor-Positive Breast Carcinoma

Study ID

NCT05464810

Start date

Sep 2, 2022

Status verified date

Jul, 2026

Completion date

Apr 15, 2028

Anticipated

Primary completion date

Apr 15, 2027

Anticipated

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Age >= 18 years
Biopsy proven hormone receptor positive, HER2 negative stage I-III invasive breast cancer

Estrogen receptor (ER) and/or progesterone receptor (PR) positivity are defined as >= 10% of cells expressing hormonal receptors via IHC analysis
HER2 negativity is defined as either of the following by local laboratory assessment

IHC 0, 1+, or 2+ and in situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell)
Minimum primary tumor size 5 mm on any breast imaging (mammogram, ultrasound, magnetic resonance imaging \[MRI\])
Baseline Ki-67 IHC expression on tumor tissue >= 10%
Post-menopausal women

Prior bilateral oophorectomy
Age >= 55 years
Age < 55 and amenorrheic for 12 months or more in the absence of chemotherapy, endocrine therapy, or ovarian suppression and follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol in the postmenopausal range
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Prior treatment:

No systemic therapy (chemotherapy, immunotherapy, endocrine therapy, and/or investigational therapy) within 3 months of trial enrollment
No statins, fibrates, or ezetimibe within 3 months of trial enrollment
No active liver disease
Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] >= 9.0 g/dl is acceptable) (within 14 days prior to initiation of study treatment)
Absolute neutrophil count (ANC) >= 1,500/mcL (after at least 7 days without growth factor support or transfusion) (within 14 days prior to initiation of study treatment)
Platelets >= 100,000/mcL (within 14 days prior to initiation of study treatment)
Total bilirubin =< 2 institutional upper limit of normal (ULN) (within 14 days prior to initiation of study treatment)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 institutional ULN (within 14 days prior to initiation of study treatment)
Serum creatinine =< 2 mg/dL (or glomerular filtration rate >= 40 mL/min) (within 14 days prior to initiation of study treatment)
Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
Be willing and able to provide written informed consent for the trial

Exclusion Criteria:

Patients who are receiving any other investigational agents or an investigational device within 3 months before administration of first dose of study drugs
History of allergic reactions attributed to compounds of similar chemical or biologic composition to simvastatin and/or letrozole
Concomitant use of strong CYP3A4 inhibitors (i.e. clarithromycin, erythromycin, itraconazole, ketroconazole, nefazodone, Posaconazole, voriconazole, protease inhibitors \[including boceprevir and telaprevir\], telithromycin, cobicistat-containing products), cyclosporine, danazol, and gemfibrozil
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, substance abuse disorders, or psychiatric illness/social situations that would limit compliance with study requirements
Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association class 3 or 4 congestive heart failure; or uncontrolled grade >= 3 hypertension (diastolic blood pressure >= 100 mmHg or systolic blood pressure >= 160 mmHg) despite antihypertensive therapy
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (letrozole, simvastatin)

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

active comparator: Arm II (letrozole)

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

Interventions

Letrozole

Given PO

Simvastatin

Given PO

Primary outcome measure

Mean percentage change in Ki-67 [ Time Frame: From pre-surgical baseline to 14 days following preoperative therapy ]

Central Contacts and Locations

Central contacts

Ruth L. Sacks, MD

404-778-1345 ruth.lauren.sacks@emory.edu

Locations

Grady Healthcare System

Recruiting

Atlanta, Georgia, United States, 30303

Contacts

Obi Ezennia

obichukwu.ezennia@emory.edu

Principal Investigator:

Ruth Sacks, MD

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Carlos E. Aguilera

404-778-4982 carlos.e.aguilera.zenteno@emory.edu

Principal Investigator:

Ruth L. Sacks, MD

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Ashley Trumbull

404-778-3969 ashley.lynn.trumbull@emory.edu

Principal Investigator:

Ruth L. Sacks, MD

Emory Saint Joseph's Hospital

Recruiting

Atlanta, Georgia, United States, 30342

Contacts

Jody Ewing

678-843-7029 jody.ewing@emory.edu

Principal Investigator:

Ruth L. Sacks, MD

More Information

Sponsor

Emory University

Last update posted

Jul 17, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2026-07-17.