AzTrials
AzTrials

Anatomic Stage I Breast Cancer AJCC v8Early Phase 1NCT05464810

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

A Early Phase 1 study testing Letrozole and Simvastatin in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Emory University at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Letrozole and Simvastatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
4 sitesUnited States
Study dates
2 Sep 2022to 15 Apr 2028
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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])
Show all 24Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States4 sites, 4 recruiting
  • Grady Healthcare System

    Atlanta, Georgia, 30303

    Obi Ezennia, obichukwu.ezennia@emory.edu

    Ruth Sacks, MD

    Recruiting
  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

    Carlos E. Aguilera, 404-778-4982, carlos.e.aguilera.zenteno@emory.edu

    Ruth L. Sacks, MD

    Recruiting
  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Ashley Trumbull, 404-778-3969, ashley.lynn.trumbull@emory.edu

    Ruth L. Sacks, MD

    Recruiting
  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

    Jody Ewing, 678-843-7029, jody.ewing@emory.edu

    Ruth L. Sacks, MD

    Recruiting

Other trials in United States

About this study

Official title: A Randomized Window of Opportunity Study of Preoperative Letrozole and Simvastatin Versus Letrozole Alone in Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine if the addition of simvastatin to letrozole compared to letrozole alone will result in a decrease of Ki67, a biomarker of tumor proliferation, in postmenopausal women with stage I-III, hormone receptor positive, HER2 negative breast cancer following 14 days of pre-surgical therapy.

SECONDARY OBJECTIVES:

  1. To determine if the addition of simvastatin to letrozole compared to letrozole alone will result in increased immune activation from pre- to post-treatment, based on the evaluation of the immune subtype composition in the tissue via multiplex immunofluorescence.

II. To determine if changes (from pre- to post-treatment) in immune activation correlate with changes in antiproliferative response, based on Ki-67 (from pre- to post-treatment).

III. To identify an association between response defined per percent change in Ki-67 and the percentage of tissue immune biomarkers CD8 and FOXp3.

IV. To determine if the addition of simvastatin to letrozole compared to letrozole alone will result in increased pain based on Patient-Reported Outcomes Measurement Information System (PROMIS) from pre- to post-treatment.

  1. To describe the safety and tolerability of letrozole +/- simvastatin in the pre-surgical setting.

EXPLORATORY OBJECTIVES:

  1. In both arms of the trial, assess the levels of blood-based biomarkers (CRP, IL-6, IL-10, TGF-beta, and TNF-alpha) in pre- and post-treatment blood samples.

Ia. Determine if changes (from pre- to post-treatment) in the levels of these blood-based biomarkers correlate with changes in antiproliferative response, based on Ki67 (from pre- to post-treatment).

Ib. Determine if changes (from pre- to post-treatment) in the levels of these blood-based biomarkers correlate with changes in immune activation, based on the evaluation of the immune subtype composition in the tissue via multiplex immunofluorescence (from pre- to post-treatment).

II. In both arms of the trial, assess fasting total cholesterol levels in pre- and post-treatment blood samples to determine if there is a correlation with changes in antiproliferative response, based on Ki67 (from pre- to post-treatment).

III. In both arms of the trial, assess HMG-CoA Reductase immunohistochemistry (IHC) expression in pre- and post-treatment tumor tissue to determine if there is a correlation with changes in antiproliferative response, based on Ki67 (from pre- to post-treatment).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive letrozole orally (PO) once daily (QD) and simvastatin PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

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

After completion of study treatment, patients are followed for 30 days.

Being tested
Letrozole, Simvastatin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LetrozoleDrug

    Also called CGS 20267, Femara

    Given PO

  • SimvastatinDrug

    Also called MK 733, Synvinolin, Zocor

    Given PO

Study groups in NCT05464810
Study groupRoleWhat they receive
Arm I (letrozole, simvastatin)ExperimentalPatients receive letrozole PO QD and simvastatin PO QD for 14 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Letrozole; Drug: Simvastatin
Arm II (letrozole)Active comparatorPatients receive letrozole PO QD for 14 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean percentage change in Ki-67

    Negative change denotes reduction. Ki-67 is a validated surrogate marker for disease-free survival in patients with hormone receptor positive (HR+), HER2- breast cancer. Ki-67 values at 14 days are expressed as geometric mean proportions of the baseline and transformed into percentage change. Geometric mean percentage change of Ki-67 from pre- to post-treatment is calculated and compared between the two treatment arms. A two-sided Mann-Whitney U or Wilcoxon Rank-Sum test is used.

    Measured: From pre-surgical baseline to 14 days following preoperative therapy

Secondary outcomes (4)
  1. Response per Ki-67

    Responders are defined as those with >= 40% pre- to post-treatment decrease in Ki-67, and non-responders are those with < 40% decrease in Ki-67. Descriptive statistics (mean, standard deviation, median, min, max) are applied to biomarkers of interest at 2 designated time points, prior to preoperative therapy (utilizing archival tissue from baseline biopsy) and following completion of 14 days of preoperative therapy. Absolute change or percentage change of biomarkers is calculated and compared between the two treatment arms using the nonparametric Mann-Whitney U test. Correlation among biomarkers is described by Pearson correlation coefficient with 95% confidence interval. The p-value is adjusted by Benjamini-Hochberg procedure to control the false discovery rate.

    Measured: Through study completion, an average of 1 year

  2. Change in the level of the following immune biomarkers: Percentage of CD8+ T cells, percentage of FOXp3 Treg cells, ratio of CD8+/Treg ratio

    Based on multiplex immunofluorescence. Descriptive statistics (mean, standard deviation, median, min, max) are applied to biomarkers of interest at 2 designated time points, prior to preoperative therapy (utilizing archival tissue from baseline biopsy) and following completion of 14 days of preoperative therapy. Absolute change or percentage change of biomarkers is calculated and compared between the two treatment arms using the nonparametric Mann-Whitney U test. Correlation among biomarkers is described by Pearson correlation coefficient with 95% confidence interval. The p-value is adjusted by Benjamini-Hochberg procedure to control the false discovery rate.

    Measured: Through study completion, an average of 1 year

  3. Patient-Reported Outcomes Measurement Information System (PROMIS) for pain

    Measured: Up to 30 days after surgery

  4. Incidence of adverse events

    Evaluated per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 criteria. Adverse events are summarized descriptively using frequencies and percentages of all captured toxicities and grades using CTCAE v.5 criteria.

    Measured: Up to 30 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2022
  2. Study start2 Sep 2022
  3. Primary completion15 Apr 2027 (estimated)
  4. Study completion15 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05464810
Sponsor's protocol ID
STUDY00004257
Other IDs
NCI-2022-02545, STUDY00004257, WINSHIP5524-22, P30CA138292
Status last verified
Jul 2026
First submitted
24 Jun 2022
Last updated
17 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Letrozole and Simvastatin in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Emory University at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ruth L. Sacks, MD (404-778-1345, ruth.lauren.sacks@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean percentage change in Ki-67 (time frame: From pre-surgical baseline to 14 days following preoperative therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in