Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer
Condition: Breast Adenocarcinoma; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; HER2/Neu Negative; Invasive Breast Carcinoma
MeSH terms: Breast Neoplasms
Intervention: Laboratory Biomarker Analysis; Talazoparib
Intervention description: Correlative studies; Given PO
Intervention MeSH terms: Talazoparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects of talazoparib when given before standard
      therapy in treating patients with breast cancer that has spread to nearby healthy tissue and
      has a mutation in a breast cancer, early onset (BRCA) gene. Talazoparib may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth, and may be especially
      effective in patients with BRCA mutations. It is not yet known whether adding talazoparib
      before standard treatment is safe in treating patients with BRCA mutated breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed written informed consent

          -  Histologically confirmed primary invasive adenocarcinoma of the breast with the size
             of the primary tumor being at least 1 cm on imaging by either mammography, ultrasound
             or breast magnetic resonance imaging (MRI)

          -  Negative human epidermal growth factor receptor 2 (HER-2)/neu- disease defined as
             patients with fluorescence in situ hybridization (FISH) ratio < 2.0 or < 6.0 HER2 gene
             copies per nucleus, and IHC staining scores of 0, 1+, or 2+

          -  No treatment for current primary invasive adenocarcinoma of the breast such as
             irradiation, chemotherapy, immunotherapy, investigational therapy or surgery; previous
             treatment for breast and/or ovarian cancer with chemotherapy, endocrine therapy,
             surgery and radiation are allowed if >= 3 years prior to current diagnosis and there
             is no clinical evidence of metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Baseline multi gated acquisition scan (MUGA) or echocardiogram scans with left
             ventricular ejection fraction (LVEF) of > 50%

          -  Absolute neutrophil count (ANC) >= 1,500/uL

          -  Platelets >= 100,000/uL

          -  Hemoglobin (Hgb) >= 9 g/dL

          -  Creatinine clearance > 50 ml/min

          -  Total bilirubin =< 1.5 X upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN

          -  Negative serum or urine pregnancy test for women within 7 days of receiving the first
             dose of the study medication for women of childbearing potential; women will be
             considered not of childbearing potential and exempt from pregnancy testing if they are
             either a) older than 50 and amenorrheic for at least 12 consecutive months following
             cessation of all exogenous hormonal treatments, or b) have documentation of
             irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or
             bilateral salpingectomy, but not tubal ligation

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for up to 8 weeks after the
             last dose of investigational product; men on study also must be using contraception

          -  Identified deleterious mutation in BRCA 1 or 2 genes (this does not include variants
             of uncertain significance)

          -  Eligible to receive standard of care chemotherapy and/or surgery based upon standard
             practices or institutional guidelines

        Exclusion Criteria:

          -  Women who are pregnant (including positive pregnancy test at enrollment or prior to
             study drug administration) or breast-feeding

          -  Disease free of prior malignancy for < 3 years with the exception of curatively
             treated basal carcinoma of the skin or carcinoma in situ of the cervix

          -  Any other previous antitumor therapies for the current cancer event

          -  Has had major surgery within 21 days before cycle 1 day 1

          -  Gastrointestinal tract disease or defect with associated malabsorption syndrome

          -  Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

          -  Myocardial infarction within 6 months before starting therapy, symptomatic congestive
             heart failure (New York Heart Association > class II), unstable angina, or unstable
             cardiac arrhythmia requiring medication

          -  Serious intercurrent infections or non-malignant medical illness that are uncontrolled
             or the control of which may be jeopardized by this therapy

          -  Psychiatric disorders or other conditions rendering the subject incapable of complying
             with the requirements of the protocols

          -  Unable to take oral medications

          -  Known to be human immunodeficiency virus positive

          -  Known active hepatitis C virus, or known active hepatitis B virus

          -  Concurrent disease or condition that would interfere with study participation or
             safety, such as any of the following:

               -  Active, clinically significant infection either grade > 2 by National Cancer
                  Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version
                  (v)4.03 or requiring the use of parenteral anti-microbial agents within 14 days
                  before day 1 of study drug

               -  Clinically significant bleeding diathesis or coagulopathy, including known
                  platelet function disorders

               -  Non-healing wound, ulcer, or bone fracture

          -  Known hypersensitivity to any of the components of talazoparib