Exemestane and Cyclophosphamide for Metastatic Breast Cancer
Exemestane and Cyclophosphamide for Metastatic Breast Cancer
This phase II trial studies how well exemestane and cyclophosphamide work in treating
 patients with estrogen receptor (ER) -positive, progesterone receptor (PR) -positive, and
 human epidermal growth factor receptor (HER)2-negative stage IV breast cancer.
Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may
 fight breast cancer by blocking the use of estrogen by the tumor cells. Low dose
 cyclophosphamide may also stimulate the white blood cells, including natural killer cells,
 for instance by decreasing the suppressor (regulatory) T-cells. Giving exemestane with
 cyclophosphamide may be an effective treatment for estrogen receptor-positive, progesterone
 receptor-positive, and HER2-negative stage IV breast cancer.
Inclusion Criteria:

 -  Patients must have histologically confirmed breast cancer that is ER positive and/or
 PR positive, and HER2/neu negative and have disease that is metastatic (stage IV)

 -  HER2/neu negative disease determined using commercially available/approved assay
 in local institutional or reference laboratory, according to American Society of
 Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (IHC
 0-1+ or 2+ with HER2/17 ratio on FISH <= 1.8).

 -  ER/PR expression performed by standard immunohistochemical assay and classified
 as ER and/or PR-positive according to ASCO/CAP guidelines (1-100% expression)

 -  Histologic and/or cytologic confirmation of metastatic disease is encouraged
 whenever feasible, furthermore, if feasible, the biopsy should confirm that the
 metastatic tumor is ER and/or PR positive and HER2/neu negative. For patients in
 whom histologic biopsy confirmation and/or assessment of ER/PR/HER2 of metastatic
 disease is not feasible, it is required that the primary tumor be ER and/or
 PR-positive and HER2/neu negative.

 -  Measurable disease (RECIST 1.1) or non-measurable (assessable) disease

 -  Patients must have had progressive disease during at least one line of endocrine
 therapy for metastatic disease or have recurrent disease while or within 12 months of
 receiving adjuvant endocrine therapy. Prior treatments accepted include a
 non-steroidal aromatase inhibitor, tamoxifen, fulvestrant or combinations.

 -  Patients taking bisphosphonates for bone disease are permitted to enter the trial, but
 their bone lesions are not considered to be assessable for response, although they are
 assessable for progression.

 -  Female or male subjects age >= 18 years.

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

 -  Patients must have normal organ and marrow function as defined below:

 -  absolute neutrophil count >= 1,200/mcL

 -  platelets >= 100,000/mcL

 -  hemoglobin >= 9g/dl

 -  total bilirubin <= 2 X upper limit of normal (ULN) [unless due to Gilbert's disease]

 -  AST(SGOT) <= 2.5 X ULN

 -  ALT(SGPT) <= 2.5 X ULN

 -  creatinine <= 1.5 X ULN

 -  Patients must be able to swallow and tolerate oral medications.

 -  Postmenopausal status, defined as 60 years and older, being 45 years and older and
 having amenorrhea x 12 months or follicle stimulating hormone levels within
 postmenopausal range, OR having undergone a bilateral oophorectomy.

 -  Ability to understand and the willingness to sign a written informed consent document.

 Exclusion Criteria:

 -  Patients may not be receiving any other investigational agents.

 -  Prior treatment for breast cancer with a steroidal aromatase inhibitor; with the
 exception of patients who were started on the combination of exemestane with
 everolimus less than 4 weeks prior to study entry and discontinued everolimus due to
 poor tolerability.

 -  Presence of life threatening metastatic visceral disease (defined as extensive hepatic
 involvement or symptomatic pulmonary lymphangitic spread) or uncontrolled brain
 metastases.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements.