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

NCT05464810 | Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00004257NCI-2022-02545WINSHIP5524-22P30CA138292
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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; Invasive Breast Carcinoma

Outcome Measures

Primary Outcomes (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.

  From pre-surgical baseline to 14 days following preoperative therapy

Secondary Outcomes (4)

• Response per Ki-67

  Through study completion, an average of 1 year

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

  Through study completion, an average of 1 year

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

  Up to 30 days after surgery

• Incidence of adverse events

  Up to 30 days after surgery

Other Outcomes (3)

• Changes in the level of immune activation in the blood using blood-based biomarkers (CRP, IL-6, IL-10, TGF-beta, TNF-alpha)

  Through study completion, an average of 1 year

• Changes in total cholesterol levels in the blood

  Through study completion, an average of 1 year

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

  Through study completion, an average of 1 year

Study Arms (2)

Arm I (letrozole, simvastatin)

EXPERIMENTAL

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

Drug: Letrozole; Drug: Simvastatin

Arm II (letrozole)

ACTIVE COMPARATOR

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

Drug: Letrozole

Interventions

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Arm I (letrozole, simvastatin); Arm II (letrozole)

Simvastatin DRUG

Given PO

Also known as: MK 733, Synvinolin, Zocor

Arm I (letrozole, simvastatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Grady Healthcare System

Atlanta, Georgia, 30303, United States

RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

MeSH Terms

Interventions

Letrozole; Simvastatin

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Ruth L. Sacks, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth L. Sacks, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Pathologists are blinded to each other's data and data from earlier analyses of samples.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 24, 2022
• First Posted: July 19, 2022
• Study Start: September 2, 2022
• Primary Completion: April 15, 2026
• Study Completion (Estimated): April 15, 2027
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

US (4)