Combining letrozole and simvastatin to treat hormone receptor positive breast cancer
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 study tests if combining letrozole with simvastatin can help shrink tumors in postmenopausal women with hormone receptor positive breast cancer better than using letrozole alone.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | Emory University Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy |
| Locations | 4 sites (Atlanta, Georgia and 3 other locations) |
| Trial ID | NCT05464810 on ClinicalTrials.gov |
What this trial studies
This early phase I trial investigates the effectiveness of combining letrozole with simvastatin compared to letrozole alone in reducing tumor cell proliferation in postmenopausal women with stage I-III hormone receptor positive, HER2 negative breast cancer. The primary objective is to measure the decrease in Ki67, a biomarker for tumor growth, after 14 days of treatment. Secondary objectives include assessing immune activation changes and their correlation with tumor response, as well as evaluating safety and tolerability. The study aims to provide insights into the potential benefits of this combination therapy in a pre-surgical setting.
Who should consider this trial
Good fit: Ideal candidates are postmenopausal women aged 18 and older with biopsy-proven hormone receptor positive, HER2 negative stage I-III invasive breast cancer.
Not a fit: Patients with HER2 positive breast cancer or those who are not postmenopausal may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could enhance treatment efficacy for patients with hormone receptor positive breast cancer.
How similar studies have performed: While the combination of letrozole and simvastatin is a novel approach, similar studies have shown promise in enhancing cancer treatment outcomes.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Atlanta, Georgia and 3 other locations
- Grady Healthcare System — Atlanta, Georgia, United States (Recruiting)
- Emory University Hospital Midtown — Atlanta, Georgia, United States (Recruiting)
- Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States (Recruiting)
- Emory Saint Joseph's Hospital — Atlanta, Georgia, United States (Recruiting)
Study contacts
- Principal investigator: Ruth L. Sacks, MD — Emory University Hospital/Winship Cancer Institute
- Study coordinator: Ruth L. Sacks, MD
- Email: ruth.lauren.sacks@emory.edu
- Phone: 404-778-1345
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.