Inclusion Criteria

- INCLUSION CRITERIA:

- Must have metastatic, progressive, castrate-resistant prostate cancer (CRPC). There
must be radiographic evidence of disease after primary treatment with surgery or
radiotherapy that has continued to progress radiographically or biochemically (rising

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 the 6 months.

-Histopathological confirmation of prostate cancer by the Laboratory of Pathology of the
NCI or Pathology Department of the National Naval Medical Center prior to entering this
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 CT scan,
MRI, or calipers by clinical exam.

- Patients participating in the study after the run-in phase must not have had prior
chemotherapy for metastic disease; patients participating in the run-in phase may be
either pre- or postchemotherapy.

- Patients may not have had more than 7 days of treatment with ketoconazole by mouth in
the past 6 months.

- Males greater than or eqaul 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.

- ECOG performance status less than or equal to 2.

- Life expectancy of > 3 months.

- Adequate bone marrow, hepatic, and renal function with:

Leukocytes greater than or equal to 3000/mu L

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

AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional upper limits of
normal

PTT or aPTT less than or equal to 1.5 times ULN per institutional laboratory range and INR
less thanor 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

CrCl (mL/min) = (140-age) times actual body weight (kg)
(times 0.85
for females)

72 times serum creatinine (mg/dL)

Urinary protein less thanor equal to 30 mg/dL in urinalysis or less than or equall 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 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 reasonand
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 useadequate
contraception prior to the study, for the duration of study participation, and 6months
after completion of AMG 386 administration.

-Must have the ability to understand and the willingness to sign a written informed
consent document.

EXCLUSION CRITERIA:

- 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.

- Have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior
to entering the study.

- 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.

- 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.