AMG 386 and Abiraterone for Advanced Prostate Cancer

* INCLUSION CRITERIA: * Must have metastatic, progressive, castrate-resistant prostate cancer (CRPC) with radiographic evidence of disease that has continued to progress radiographically or biochemically (rising prostatic specific antigen (PSA) levels on successive measurements) despite adequate androgen-deprivation therapy. If patients had been on flutamide, disease progression is documented 4 weeks or more after withdrawal. For patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal. Flutamide, nilutamide and bicalutamide disease progression requirements only apply to patients who have been on these drugs for at least the prior 6 months. * Histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI) or Walter Reed National Military Medical Center prior to entering this study. Patients enrolled at participating sites may have histopathological confirmation at the enrolling center prior to entering the study. Patients whose pathology specimens are no longer available may be enrolled if the patient has a clinical course that is consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. All efforts should be made to have the material forwarded to the research team for use in correlative studies in cases where original tissue blocks or archival biopsy material is available. * Patients must have metastatic disease, defined as at least one lesion on bone scan or at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam. * Patients participating in the study must have Metastatic Castration-Resistant Prostate Cancer (mCRPC). * Patients who have received docetaxel plus androgen deprivation therapy (ADT) for metastatic castrate sensitive prostate cancer are eligible for the study. (Patients may enroll as long as they did not have progressive disease while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1.) * Patients may not have had more than 7 days of treatment with ketoconazole by mouth in the past 6 months. * Males greater than or equal to 18 years of age. Because no dosing or adverse event data are currently available on the use AMG 386 in combination with abiraterone in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 for run-in phase; ECOG less than or equal to 1 for randomized phase. * Life expectancy of \> 3 months for the run in phase and \> 6 months for the randomized phase. * Adequate bone marrow, hepatic, and renal function with: * Leukocytes greater than or equal to 3000/mu L * Absolute neutrophil count (ANC) greater than or equal to 1500/mu L * Platelets greater than or equal to 100000/mu L * Total bilirubin less than or equal to 1.5 times institutional upper limits of normal * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 times institutional upper limits of normal * Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) less than or equal to 1.5 times upper limits of normal (ULN) per institutional laboratory range and international normalized ratio (INR) less than or equal to 5 * Creatinine less than or equal to 1.5 times institutional upper limits of normal OR * Creatinine clearance of \>40 mL/min per 24 h urine collection or calculated according to the Cockcroft-Gault formula ---Creatinine clearance (CrCl) (mL/min) = (((140-age) times actual body weight (kg))/(72 x serum creatinine (mg/dL)))\*(x 0.85 for females) * Urinary protein less than or equal to 30 mg/dL in urinalysis or less than or equal to1+ on dipstick, unless quantitative protein is \<1000 mg in a 24h urine sample * Generally well-controlled blood pressure with systolic blood pressure less than or equal to 140 mmHg AND diastolic blood pressure less than or equal to 90 mmHg prior to enrollment. The use of antihypertensive medications to control hypertension is permitted. * Must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 Common Terminology Criteria in Adverse Events (CTCAE) version 4 or has returned to baseline. Alopecia \>grade 1 is permitted. * The effects of AMG 386 on the developing human fetus are unknown. For this reason and because inhibitors of angiogenesis as well as other therapeutic agents used in this trial are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of AMG 386 administration. -Must have the ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: * Patients who have had chemotherapy for metastatic castration-resistant prostate cancer. * History or presence of known central nervous system metastases. * History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization. * History of clinically significant bleeding within 6 months of enrollment/randomization. * Currently or previously treated with AMG 386, or other molecules that primarily inhibit the angiopoietins or Tie2 receptor. * Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent. * Major surgery within 28 days prior to enrollment or still recovering from prior surgery. * Minor surgical procedures, placement of tunneled central venous access device within 3 days prior to randomization/enrollment. * Treatment within 30 days prior to enrollment with the following: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab. * Patients who have had large field radiotherapy must wait 2 weeks prior to entering the study. * Non-healing wound, ulcer (including gastrointestinal), or fracture. * Contraindication to steroid use or history of allergic reactions attributable to the study compounds. * History of allergic reactions to bacterially-produced proteins. * Previously diagnosed with another malignancy, within the past two years with the exception of non-melanoma skin cancers or non-invasive bladder cancer. * Patients who have not yet completed at least 28 days (30 days for prior monoclonal antibody therapy) since receiving other investigational drugs. * Inability to absorb abiraterone after oral administration (i.e., previous major gastrointestinal surgery or gastrointestinal disease resulting in malabsorption). * Use of ketoconazole, itraconazole, ritonavir, cyclosporine, carbamazepine, phenytoin, phenobarbital within 2 weeks prior to and while on study therapy. * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. * Uncontrolled intercurrent illness or infections, unstable angina pectoris, cardiac arrythmias, renal dysfunction, or psychiatric illness/social situations that would limit compliance with study requirements. * Have had treatment with docetaxel for the treatment of metastatic castrate-sensitive prostate cancer within 6 months before the first dose of study enrollment. * Have had progression of prostate cancer on prior docetaxel treatment for castrate sensitive disease.