Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer
Condition: HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: capecitabine; cyclophosphamide; lapatinib ditosylate; trastuzumab; laboratory biomarker analysis
Intervention description: Given PO; Given PO; Given PO; Given IV; Correlative studies
Intervention MeSH terms: Cyclophosphamide; Capecitabine; Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well capecitabine, cyclophosphamide, lapatinib ditosylate,
      and trastuzumab work in treating patients with human epidermal growth factor receptor 2
      (HER2)-positive metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine
      and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Giving capecitabine and cyclophosphamide
      daily may kill more tumor cells. Lapatinib ditosylate may stop the growth of tumor cells by
      blocking some of the enzymes needed for growth. Monoclonal antibodies, such as trastuzumab,
      can block tumor growth in different ways. Some block the ability of the tumor to grow and
      spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Giving capecitabine, cyclophosphamide, lapatinib ditosylate, and trastuzumab together may be
      an effective treatment for breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed HER2-positive metastatic breast cancer

          -  HER2 overexpression of tumor by either immunohistochemistry (IHC) or fluorescence in
             situ hybridization (FISH); tumors tested by IHC must be 3+ positive; tumors tested by
             FISH must have a ratio of HER2: chromosome enumeration probe (CEP)17 > 2.0; when both
             tests are performed, the FISH result must be positive

          -  Prior trastuzumab use in the adjuvant or metastatic setting

          -  No more than two prior cytotoxic chemotherapeutic regimens for metastatic breast
             cancer. In addition, prior Trastuzumab emtansine (TDM-1, Kadcyla) is allowed.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Hemoglobin >= 9 g/dL

          -  Bilirubin =< 1.5 x upper limit of normal (ULN)

          -  Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 ml/min

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN

          -  Fully recovered from toxicity due to prior therapy

          -  Capable of understanding the informed consent and complying with the protocol and
             signed the informed consent document prior to any study-specific screening procedures
             or evaluations being performed

          -  Must be able to swallow pills

          -  May have either measurable or non-measurable disease by Response Evaluation Criteria
             in Solid Tumors (RECIST) 1.1 criteria

          -  Sexually active participants must agree to use a medically accepted barrier method of
             contraception (i.e. male condom or female condom) during the course of the study and
             for 3 months following discontinuation of study treatments; for participants of
             childbearing potential, a barrier method and a second method of contraception must be
             used

          -  Participants of childbearing potential must have a negative pregnancy test at
             screening and enrollment; participants of childbearing potential are defined as
             premenopausal females capable of becoming pregnant, i.e. females who have had any
             evidence of menses in the past 12 months with the exception of those who had prior
             hysterectomy (oophorectomy or surgical sterilization); however, women who have been
             amenorrheic for >= 12 months are still considered to be of childbearing potential if
             the amenorrhea is possibly due to any other cause including prior chemotherapy,
             antiestrogens, or ovarian suppression

        Exclusion Criteria:

          -  Prior treatment with capecitabine or lapatinib

          -  Radiation therapy within 2 weeks before the first dose of study treatment

          -  Hormonal therapy within 2 weeks before the first dose of study treatment

          -  Cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3
             weeks before the first dose of study treatment

          -  Biologic therapy (including antibodies [other than trastuzumab], immune modulators,
             cytokines) within 4 weeks before the first dose of study treatment; Note: there is no
             washout period required for trastuzumab

          -  Any other type of investigational agent within 4 weeks before the first dose of study
             treatment

          -  Major surgery, or not recovered from major surgery within 4 weeks before the first
             dose of study treatment

          -  Untreated, symptomatic, or progressive brain metastases; participants must have no
             radiographic or other signs of progression in the brain for >= 1 month after
             completion of local therapy; any corticosteroid use for brain metastases must have
             been discontinued without the subsequent appearance of symptoms for >= 4 weeks prior
             to first study treatment

          -  Uncontrolled significant intercurrent illness that would preclude the patient from
             study participation per investigator assessment

          -  Left ventricular ejection fraction (LVEF) =< 50% as documented by multi gated
             acquisition scan (MUGA) or echocardiogram performed within 28 days prior to the first
             study treatment

          -  Currently receiving anticoagulation with therapeutic doses of warfarin (low-molecular
             weight heparin is permitted)

          -  Pregnant or breastfeeding

          -  Known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at
             screening is not required)

          -  Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease
             (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones,
             liver metastases or stable chronic liver disease per investigator assessment)

          -  Previously identified allergy or hypersensitivity or intolerance to components of the
             study treatment formulation (cyclophosphamide, capecitabine, lapatinib [lapatinib
             ditosylate], trastuzumab)

          -  Any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin
             cancer, in-situ carcinoma of the cervix) within 2 years prior to screening for this
             study

          -  Unable or unwilling to abide by the study protocol or cooperate fully with the
             investigator or designee