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.
Inclusion Criteria:
- Is willing and able to provide written informed consent for the trial
- Diagnosis of TNBC (including patients with a clinical diagnosis of triple negative
inflammatory breast cancer)
- Has histological confirmation of breast carcinoma
- Have stage IIB or III disease as defined by the American Joint Committee on Cancer
version 7 or 8
- Has confirmed TNBC, defined as having estrogen and progesterone receptor < 10%
positivity by immunohistochemistry (IHC) and HER2 normal, which is 0 or 1+ by IHC and
negative by fluorescence in situ hybridization (FISH) if performed or HER2 2+ by IHC
and negative by FISH or HER2 negative by FISH if IHC is not performed
- Received neoadjuvant chemotherapy and did not achieve pCR nor had an RCB-I (we will
enroll patients with an RCB-II or RCB-III) following neoadjuvant chemotherapy. Since
the RCB index has not been validated in IBC, any amount of residual disease will be
allowed. pCR is defined as: a) the absence of residual invasive cancer on hematoxylin
and eosin evaluation of the complete resected breast specimen and all sampled regional
lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0
in the current American Joint Committee on Cancer [AJCC] staging system). Or b) the
absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of
the complete resected breast specimen and all sampled regional lymph nodes following
completion of neoadjuvant systemic therapy (i.e., ypT0 ypN0 in the current AJCC
staging system)
- Has a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG)
performance scale
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelets >=100,000 /mcL
- Hemoglobin (Hgb) >= 8 g/dL
- Creatinine levels < 2.0 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN
- Subjects of childbearing potential should be willing to use effective methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through at least 4 months after the last dose of study drug; subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year; effective methods of birth control include 1). Use
of hormonal birth control methods: pills, shots/injections, implants (placed under the
skin by a health care provider), or patches (placed on the skin); 2). Intrauterine
devices (IUDs); 3). Using 2 barrier methods (each partner must use 1 barrier method)
with a spermicide. Males must use the male condom (latex or other synthetic material)
with spermicide. Females must choose either a diaphragm with spermicide, or cervical
cap with spermicide, or a sponge (spermicide is already in the contraceptive sponge)
- Within 3 months from completion of definitive surgery after neoadjuvant chemotherapy
- Willing to take statin for minimum of two years
Exclusion Criteria:
- Has not recovered from adverse events due to prior therapies, i.e. monoclonal
antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or surgery
- Note: Subjects with =< grade 2 neuropathy, alopecia and general disorders and
administration site conditions are an exception to this criterion and may qualify
for the study
- Has a known malignancy (other than breast cancer) except basal cell carcinoma or
squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone
potentially curative therapy
- Has known psychiatric or substance abuse disorders and assessed by attending physician
that would interfere with cooperation with the requirements of the trial
- Has received prior therapy with a statin within past 6 months or is currently
receiving statin therapy; patients who previously received a statin more than 6 months
prior to beginning study therapy and who discontinued treatment for reasons other than
severe toxicity or allergic reaction are eligible
- Is currently receiving another anti-lipidemic agent other than statin: fibric acid
derivatives (i.e. fenofibrate, gemfibrozil), bile acid sequestrants (i.e.
cholestyramine, colestipol), ezetimibe, niacin, lovaza (omega-3-acid ethyl esters),
red yeast rice, orlistat, phytosterol, and lomitapide
- Known hypersensitivity to statin or any component of the formulation
- Active liver disease or unexplained persistent elevations of serum transaminases,
defined as elevated transaminases > 3 x ULN on at least 2 separate occasions 1 week
apart
- Pregnancy or women who may become pregnant and not on acceptable form of
contraception; lactating women
- Has evidence of distant metastasis
- Record of myocardial infarction within 6 months before starting therapy, symptomatic
congestive heart failure (New York Heart Association > class II), unstable angina, or
unstable cardiac arrhythmia requiring medication
- Chronic steroid use as this may prevent any immunomodulatory roles of statin
treatment, defined as anticipating need of supraphysiologic dose of steroids for at
least 12 weeks while on study
