Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer

Inclusion Criteria

• •1. Patients must have histologically or cytologically confirmed breast cancer with stage IV or unresectable stage III disease.
• •2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. To be considered pathologically enlarged and measurable, a lymph node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).
• •3. Triple-negative breast cancer (defined as estrogen receptor (ER) and progesterone receptor (PR) \<10% positive; HER2 0-1+ by immuno-histochemistry (IHC) or fluorescence in situ hybridization (FISH) ratio \<2.0)
• •4. Patients must have tumor block or slides available for testing, and tumor must be glucocorticoid receptor positive (defined as GR \>10% moderate to strong staining by central lab). A formalin-fixed, paraffin-embedded surgical or core needle biopsy obtained from the primary tumor or from a metastasis and containing viable tumor tissue is required for this evaluation. Fine needle aspirates or other alternative cytology samples are not acceptable.
• •5. Patients may have received adjuvant chemotherapy and up to two prior chemotherapy for metastatic or locally recurrent disease. No prior nab-paclitaxel or mifepristone therapy for metastatic disease will be allowed.
• •6. Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of Nab-Paclitaxel in combination with Mifepristone in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• •7. Eastern Cooperative Oncology Group performance status ≤ 2 (Karnofsky ≥ 60%).
• •8. Patients must have normal organ and marrow function as defined below
• •* absolute neutrophil count \>1,500 cells/mm3.
• •* platelets ≥100,000/mcL
• •* hemoglobin \> 9.0 g/dL
• •* total bilirubin\< 1.5 mg/dL
• •* alkaline phosphatase \< 2.5 X upper limit of normal (ULN) or \< 5 X ULN if bone mets are present
• •* aspartate aminotransferase (AST) and Alanine transaminase (ALT) \< 2.5 ULN or \< 5 X ULN if liver mets are present
• •* adequate renal function: creatinine ≤ institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• •* international normalized ratio (INR) \< 1.5
• •9. Females of child-bearing potential (defined as a sexually mature woman who has not undergone hysterectomy, bilateral oophorectomy, or who has not been naturally postmenopausal for at least 24 consecutive months prior to study enrollment) must:
• •* Commit to abstinence from heterosexual contact or agree to use effective contraception without interruption beginning at least 28 days prior to starting protocol therapy and while on study medication.
• •* Have a negative serum pregnancy test result at screening and agree to ongoing pregnancy testing during the study dosing
• •10. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following protocol discontinuation, even if he has undergone a successful vasectomy.
• •11. Patients must have \< Grade 2 pre-existing peripheral neuropathy (per CTCAE).
• •12. Ability to understand and the willingness to sign a written informed consent document.