Study of XL147 (SAR245408) in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-based Regimen

Inclusion Criteria:

* The subject has pathologically and radiologically confirmed metastatic HER2 positive breast cancer (Stage IV disease). Subjects must have received and progressed on at least one prior trastuzumab-containing regimen for metastatic disease. For subjects in Arm 2, they must also have received at least one prior taxane-containing regimen.
* The subject has at least one lesion that is not within a previously radiated field and measurable on computerized tomography (CT) or magnetic resonance imaging scan (MRI)
* The subjects enrolled in Phase 2 must be willing to undergo a biopsy of the primary tumor or a tumor metastasis at baseline, if tumor tissue is amenable to biopsy
* The subject's primary tumor and/or metastatic lesion must overexpress HER2
* For subjects enrolled in Phase 2: samples from archival or fresh tissue, or a tissue block of the subject's tumor.
* The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* The subject has adequate organ and marrow function
* The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document prior to any study-specific screening procedures or evaluations being performed.
* Sexually active subjects must agree to use a medically-accepted barrier method of contraception during the course of the study and for 3 months following discontinuation of study treatments. For subjects using oral contraceptives, a barrier method must be used in addition to the oral contraceptive
* Subjects of childbearing potential must have a negative pregnancy test at screening and enrollment

Exclusion Criteria:

* The subject has previously been treated with a selective inhibitor of PI3K and / or AKT
* Certain restrictions on prior therapies apply
* The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline
* The subject has untreated, symptomatic, or progressive brain metastases. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥4 weeks prior to first study treatment
* The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results at screening that are ≥ 1.3 times above the laboratory upper limit of normal
* The subject has a diagnosis of uncontrolled diabetes mellitus
* The subject has uncontrolled significant intercurrent illness
* The subject has uncontrolled hypertension or other clinically significant cardiovascular disease
* The subject has left ventricular ejection fraction (LVEF) ≤ 50%
* The subject has a baseline corrected QT interval ≥ 460 ms
* The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day is permitted)
* The subject is pregnant or breastfeeding
* The subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required)
* The subject has 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
* The subject has a previously identified allergy or hypersensitivity or is intolerant to components of any of the study treatment formulations
* The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee