Entinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery
Condition: Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Triple-negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: entinostat; anastrozole; diagnostic laboratory biomarker analysis; therapeutic conventional surgery
Intervention description: orally; Given PO; Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery.
Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.; Lumpectomy or mastectomy will be performed follwoing day 29 of study therapy
Intervention MeSH terms: Anastrozole; Entinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: no masking
Masking: None (Open Label)
Masking description: no masking
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving entinostat and anastrozole together works in
      treating postmenopausal women with triple-negative breast cancer that can be removed by
      surgery. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using
      anastrozole may fight breast cancer by blocking the use of estrogen by the tumor cells.
      Giving entinostat together with anastrozole may be an effective treatment for breast cancer.
    

Eligibility criteria:

        Inclusion Criteria

          -  Female greater than or equal to 18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status <2 (see Appendix A).

          -  Histologically confirmed adenocarcinoma of the breast.

          -  Evidence of hormone insensitivity (ER and PR negative) of primary tumor tissue. ER
             negative is define as ER 0 or < 1% staining by immunohistochemistry. PR negativity is
             defined as PR < 1% staining by immunohistochemistry.

          -  HER2 negative in the primary tumor tissue as defined by:

               -  Immunohistochemistry (IHC) Grade 0 as defined by no staining observed or membrane
                  staining that is incomplete and is faint/barely perceptible and within ≤10% of
                  the invasive tumor cell

               -  IHC 1+ as defined by incomplete membrane staining that is faint/barely
                  perceptible and within >10% of the invasive tumor cell

               -  IHC Grade 2+ staining intensity by means of IHC analysis with no gene
                  amplification below.

               -  No gene amplification on ISH based on

                    -  Single-probe average HER2 copy number <4.0 signals/cell

                    -  Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0
                       signals/cell

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Patients must not have received any prior chemotherapy, radiation therapy, or
             endocrine therapy for their current breast cancer. Patients who received tamoxifen or
             raloxifene or another agent for prevention of breast cancer may be included as long as
             the patient has discontinued the treatment at least one month prior to baseline study
             biopsy.

          -  Women of childbearing potential must have negative (serum or urine) pregnancy test
             within 7 days prior to registration.

          -  Patients must have adequate tumor tissue sample prior to the enrolment available for
             correlative studies as defined below:

               -  Core needle biopsy or incisional biopsy samples that can provide ≥ 3 unstained
                  sections of 5 micron thickness. Fine needle aspiration (FNA) sample alone is not
                  sufficient except in the second cohort.

               -  Additional core needle biopsy needs to be performed in the patients who agree to
                  participate in this study and do not have adequate tumor tissue sample.

          -  Patients must have adequate organ and marrow function as defined below:

               -  Hemoglobin ≥ 9.0 g/dL

               -  Leukocytes >2,500/mcL

               -  Absolute neutrophil count >1,100/mcL

               -  Platelets >100,000/mcL

               -  Total bilirubin within normal institutional limits

               -  AST(SGOT)/ALT(SGPT) <2.5 x institutional upper limit of normal

               -  Creatinine within normal institutional limits or creatinine clearance ≥ 60
                  mL/min/1.73 m2 for patients with creatinine levels above institutional normal

        Additional Inclusion Criteria for the First cohort:

        - Unresected operable breast cancer that meets the following clinical stages (see Appendix
        B):

          -  T1b, T1c, or T2

          -  N0 or N1

          -  M0 (No distant metastasis)

        Additional Inclusion Criteria for the Second cohort:

          -  Unresectable, inoperable, recurrent local-regional breast cancer or

          -  Metastatic (stage IV) breast cancer

          -  Patients must have measurable or evaluable disease (i.e. ascites or
             pleural/pericardial effusion). Patients with bone metastatic only will be excluded.

          -  Patients must not have rapidly progressive disease, extensive visceral involvement, or
             any high risk characteristics that are not appropriate for this treatment as per
             investigator's discretion.

          -  Patients must receive at least one prior line of chemotherapy but not more 2 prior
             chemotherapy regimens for stage IV breast cancer. Prior chemotherapy in the adjuvant
             and /or neoadjuvant setting is permitted. However, patients must have finished
             chemotherapy at least 2 weeks prior to enrollment.

          -  Patients must have an accessible tumor lesion from which a fine needle aspirate or
             preferably a core biopsy specimen can be obtained. Patients with FNA only samples are
             allowed in this cohort. Ascites or pleural/pericardial effusion alone is not
             sufficient.

          -  Patients must be willing to provide consents for 2 research biopsies. However, the
             pretreatment biopsy can be omitted in patients who have recent biopsy but have not
             been started on breast cancer treatment within 12 weeks prior to the registration and
             there is adequate tumor tissue sample

        Exclusion Criteria

          -  Patients may not be receiving any other investigational agents.

          -  Prior exposure to other HDAC inhibitors. However, prior valproic acid exposure is
             allowed providing

             ≥ 30 days wash-out period.

          -  History of allergic reactions or hypersensitivity to compounds of similar chemical or
             biologic composition to entinostat, benzamide, anastrozole, or tamoxifen.

          -  Any medical condition which in the opinion of the investigator puts the patient at
             risk of potentially serious complications while on this therapy. Examples: HIV,
             unstable angina, uncontrolled heart failure or hypertension, uncontrolled
             hyperlipidemia, uncontrolled diabetes mellitus, uncontrolled systemic infection.

          -  Previous or current systemic malignancy within the past 3 years other than breast
             cancer or adequately treated cervical carcinoma in situ or basal/squamous carcinoma of
             the skin.

        Inclusion of Minorities

        - Women of all races and ethnic groups are eligible for this trial.