Study of Paclitaxel, Carboplatin, and PF-05212384 in Advanced or Metastatic NSCLC (UF-STO-LUNG-002)

Inclusion Criteria: * Signed Institutional Review Board (IRB)-approved informed consent prior to any study-related procedures * Age of 18 years or older * Advanced-stage unresectable NSCLC, as confirmed by pathological and/or radiological analysis (subjects will be classified as having advanced disease if they were not eligible for, or had disease progression after, surgical or locoregional therapies) * Prior chemotherapy will be allowed for other invasive malignancies, provided therapy was completed at least five years before the start of protocol therapy, and participants have recovered from all toxicities of that prior therapy * Participants may have received prior chemotherapy for NSCLC * In the Phase II portion, subjects must have disease which lacks PTEN expression by immunohistochemistry, or has known prior activating PI3K or inactivating PTEN gene mutations (mutations will not be assayed for specifically) * Eastern Cooperative Oncology Group (ECOG) performance status score \< 2 * Life expectancy ≥ 12 week * Participants must have measureable disease by RECIST criteria * Absolute neutrophil count \> 1500 mm3 (individuals with benign ethnic neutropenia may be enrolled if they have no evidence of infectious diathesis, or febrile neutropenia at the time of enrollment) * Platelet count ≥ 100×109 L * Hgb ≥ 8.5 g/dL (subjects may receive transfusions to achieve this, in the absence of overt bleeding) * Total Bilirubin ≤ 2 mg/dL * aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 3 times the upper limit of normal range * Serum creatinine ≤1.5 times the upper limit of the normal range * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 6 months after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: * Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or * For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. * Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 6 months following the last dose of study drug Exclusion Criteria: * Uncontrolled cardiac disease, congestive heart failure, angina, arrhythmias or hypertension. * Myocardial infarction or unstable angina within 2 months of treatment. * Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B (subjects will not be screened for this). * Active clinically serious infection \> CTCAE Grade 2. * Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. * Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug. * Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug. * Serious non-healing wound, ulcer, or bone fracture. * Evidence or history of bleeding diathesis or coagulopathy * Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug * Women or men of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 6 months after the last dose of study drug * Women who are pregnant or breastfeeding. * History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician. * Prisoners or subjects who are involuntarily incarcerated. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness. * Subjects demonstrating an inability to comply with the study and/or follow-up procedures.