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RecruitingEarly Phase 1

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
Female only
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 14 days, 30 days
  • Procedures mentioned: Blood draws

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
  • "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)."
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This early study tests whether adding simvastatin to letrozole slows breast cancer cell growth more than letrozole alone. It is for women past menopause with stage I–III invasive breast cancer that is hormone receptor positive and HER2 negative. This means the cancer can use hormones to grow and does not have high levels of the HER2 protein.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 18 or older and past menopause, as defined by the study.
  • Have stage I–III invasive breast cancer confirmed by a tissue sample. At least 10% of cells must have estrogen or progesterone receptors, and HER2 tests must be negative.
  • Have a breast tumor at least 5 millimeters wide on a breast scan.
  • Have a Ki-67 level of at least 10% in the tumor. Ki-67 is a sign of cells growing and dividing.
  • Be able to care for yourself and be out of bed or a chair for at least half of waking hours.
  • Have had no cancer treatment that works throughout the body, or cholesterol drugs called statins, fibrates, or ezetimibe, in the past 3 months.
  • Have no active liver disease. Blood cell counts and liver and kidney tests must meet study limits within 14 days before treatment starts.
  • Be willing and able to follow the study visits, treatment plan, tests, and rules, and sign a consent form.

Who can't join

  • Use of another experimental drug or device within 3 months before the first study dose.
  • Past allergic reactions to drugs similar to letrozole or simvastatin.
  • Use of certain medicines that interact with the study drugs, including some antibiotics, antifungal drugs, and antiviral drugs, or cyclosporine, danazol, or gemfibrozil.
  • An uncontrolled illness, such as an active infection or heart problem, or substance use, mental health, or social issues that would prevent following study rules.
  • A major heart or blood vessel problem within the past 3 months, such as a heart attack or a blood clot in an artery or the brain.
  • Chest pain needing treatment, poor blood flow in the limbs that causes symptoms, or severe heart failure.
  • Blood pressure of 160 or higher for the top number, or 100 or higher for the bottom number, despite treatment.
  • Another cancer that is growing or needs treatment. Some basal cell or squamous cell skin cancers treated with the aim of curing them are allowed.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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

Study sites (4)

GA