Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer

Inclusion Criteria

• •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care, and signed Health Insurance Portability and Accountability Act (HIPAA) form.
• •Female subject (≥18 years old), who is either:
• •* post-menopausal for at least one year before the screening visit, or
• •* surgically sterilized, or
• •* willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide) for the duration of the study.
• •Metastatic or locally recurrent breast cancer with histologic confirmation (on either primary or metastatic tumor) of one of the following:
• •* ER+, HER2- invasive breast cancer (any progesterone receptor \[PgR\] status)
• •* Poorly differentiated and/or Grade 3 invasive TNBC, defined as:
• •* HER2 negative status (based on most recently analyzed biopsy) is defined as immunohistochemistry (IHC) status of 0, 1+ or 2+ (if IHC 2+, a negative FISH test is required, i.e., HER2 fluorescence in situ hybridization (FISH) ratio \< 2.0 with an average HER2 copy number \<4.0 signals/cell); ER-negative and PR-negative status is defined as ER and PgR \<1% nuclei positive by IHC
• •Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) or non-measurable lytic, bone-only disease (mixed blastic/lytic bone disease is allowed); if patient has bone-predominant disease with no measurable disease, there must be a lytic component to the bone metastases that is visible on plain X-ray or CT scan that can be serially followed
• •Absolute neutrophil count (ANC) \> 1500/mm³, platelets \> 100,000/mm³, Hgb \> 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published American Society of Clinical Oncology (ASCO) guidelines (available at: http://www.asco.org/quality-guidelines/asco-ash-clinical-practice-guideline-update-use-epoetin-and-darbepoetin-adult).
• •Total bilirubin ≤ 1.5 x upper limit of normal (ULN), serum glutamic-oxaloacetic transaminase (SGOT) (AST) and serum glutamic-pyruvic transaminase (SGPT) (ALT) \< 2.5 x ULN. AST and/or ALT may be up to 5 x ULN if patient has known liver metastases
• •Adequate renal function as defined by: Calculated creatinine clearance must be ≥ 30 mL/minute (see Cockcroft-Gault formula in Appendix 5)
• •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (refer to Appendix 4)
• •Prior allogeneic bone marrow or organ transplantation
• •Known GI disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease
• •Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
• •Requirement for administration of proton pump inhibitor, or for constant administration of H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed as described in Section 3.4.
• •Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
• •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix 3), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• •Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening, within 72 hours prior to first dose of study drug(s). Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• •Patient has received an investigational agent within 30 days before enrollment
• •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.