Exemestane and Cyclophosphamide for Metastatic Breast Cancer
Condition: Metastatic Beast Cancer
Intervention: Exemestane; Cyclophosphamide
Intervention MeSH terms: Cyclophosphamide; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hormonal therapy; immunotherapy

Summary:

      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.
    

Eligibility criteria:

        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.