This phase II trial studies how well atorvastatin works in treating patients with stages IIb-III triple negative breast cancer who did not achieve a pathologic complete response to neoadjuvant chemotherapy. Pathologic complete response is the lack of all signs of cancer in tissue samples removed during surgery after upfront chemotherapy. Atorvastatin is used for the treatment of high cholesterol and may reduce the risk of triple negative breast cancer from coming back. Triple-negative breast cancer is a type of breast malignancy that is comprised of cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein. Patients with TNBC do not have established systemic therapies such as anti-estrogens or HER2-targeting agents to reduce recurrence after surgery, and residual cancer found at surgery is associated with higher relapse rate.
PRIMARY OBJECTIVES: I. To determine the proportion of patients with undetectable circulating tumor cells (CTCs) at 6 months in patients with stage IIB/III triple negative breast cancer (TNBC) who did not achieve a pathologic complete response a (pCR) or Residual Cancer Burden-I (RCB-I) after receiving neoadjuvant chemotherapy (NAC) with and without atorvastatin therapy. SECONDARY OBJECTIVES: I. To determine if baseline fasting lipid profile level (low density lipoprotein cholesterol \[LDL-C\]) and/or change in serum lipid levels are a predictive biomarker of change in the proportion of patients with CTCs. II. To assess effect of biomarkers on atorvastatin treatment response, defined as CTCs, circulating tumor deoxyribonucleic acid (DNA) (ctDNA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum Interleukin-6 (IL-6) and other inflammatory cytokines, for the purpose of identifying the optimal patient population for future larger scale adjuvant studies. III. To determine if baseline fasting lipid profile level (LDL-C) and/or change in serum lipid levels are associated with 2-year relapse free survival (RFS) rate. IV. To determine if baseline CRP and/or change in serum lipid levels are a predictive biomarker of change in the proportion of patients with CTCs. V. To determine if baseline C-reactive protein (CRP) and/or change in CRP are associated with 2-year RFS rate. VI. To determine if baseline absolute number of CTCs and/or CTC change are associated with 2-year RFS rate. VII. To estimate the 2-year RFS rate of patients with TNBC who did not achieve pCR with and without atorvastatin therapy. VIII. To describe the toxicity and adverse events profile of atorvastatin treatment when given concurrently with standard doses of radiotherapy to the chest wall and regional nodes. EXPLORATORY OBJECTIVES: I. To evaluate the correlation between multiplexed imaging biomarkers in the normal or tumor tissue taken at the time of surgery, and response to atorvastatin-induced CTC changes or with measured outcomes. OUTLINE: Patients are assigned to 1 of 2 groups. GROUP I: Patients receive standard of care atorvastatin orally (PO) once daily (QD) for up to 24 months. A physical exam is performed, and blood drawn at 3, 6, 12, 18 and 24 months after starting standard of care treatment or at any time the disease appears to get worse. GROUP II: Patients not eligible to receive atorvastatin, will be enrolled into non-statin observation group with/without capecitabine treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Patients will receive Atorvastatin per ASCVD guidelines dosed as either a moderate intensity (20mg/day) or high intensity statin (80mg/day). Tablets are available in either 20mg or 80mg and will be dispensed as per standard of care for up to 24 months as part of the study. Patients may also receive capecitabine concurrently with Atorvastatin per physician discretion as standard of care. Standard of care dosing of Capecitabine is a 21 day cycle consisting 14 days on and 7 days off. The starting dosing will be per physician discretion, but may be up to 2500mg/m2 per day.
Patients not eligible to receive atorvastatin in group II will be enrolled into non-statin observation group with/without capecitabine treatment. Capecitabine administration will be dosed as per standard of care. Standard of care dosing of Capecitabine is a 21 day cycle consisting 14 days on and 7 days off. The starting dosing will be per physician discretion, but may be up to 2500mg/m2 per day.
Banner - MD Anderson Cancer Center
Gilbert, Arizona, United States
Banner - MD Anderson Cancer Center -Northern Colorado
Greeley, Colorado, United States
Piedmont Healthcare
Atlanta, Georgia, United States
Cooper Hospital University Medical Center
Camden, New Jersey, United States
M D Anderson Cancer Center
Houston, Texas, United States
Proportions of Patients With Undetectable Circulating Tumor Cells (CTC)
Estimate the proportion of patients with undetectable circulating tumor cells (CTCs) at 6 months in patients with stage IIB/III TNBC who did not achieve a pCR or Residual Cancer Burden-I (RCB-I) after receiving neoadjuvant chemotherapy (NAC) with and without atorvastatin therapy.
Time frame: At 6 months
Fasting Lipid Profile Level (Low Density Lipoprotein Cholesterol [LDL-C]) and/or Change in Serum Lipid Levels
Determine if baseline fasting lipid profile level (LDL-C) and/or change in serum lipid levels are a predictive biomarker of change in the proportion of patients with CTCs.
Time frame: Baseline up to 2 years
Biomarkers on Atorvastatin Treatment Response
Assess effect of biomarkers on atorvastatin treatment response, defined as CTCs, circulating tumor DNA (ctDNA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum Interleukin-6 (IL-6) and other inflammatory cytokines, for the purpose of identifying the optimal patient population for future larger scale adjuvant studies.
Time frame: Up to 2 years
Fasting Lipid Profile Level (LDL-C) and 2-year RFS Rate
Fasting lipid profile level (LDL-C) and 2-year RFS rate
Time frame: Baseline up to 2 years
Baseline C-reactive Protein (CRP) and/or Change in Serum Lipid Levels
Determine if baseline CRP and/or change in serum lipid levels are a predictive biomarker of change in the proportion of patients with CTCs.
Time frame: Baseline up to 2 years
CTCs and 2-year RFS Rate
Determine if baseline absolute number of CTCs and/or CTC change are associated with 2-year RFS rate.
Time frame: Baseline up to 2 years
Recurrence-free Survival (RFS)
Estimate the 2-year RFS rate of patients with TNBC who did not achieve pCR with and without atorvastatin therapy.
Time frame: At 2 years
Incidence of Adverse Events
Adverse events, grade and relationship will be tabulated by treatment arms.
Time frame: Up to 24 months
C-reactive Protein (CRP) and 2-year RFS Rate
Determine if baseline C-reactive protein (CRP) and/or change in CRP are associated with 2-year RFS rate.
Time frame: Baseline up to 2 years
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