The primary objectives of this study are the following:

Phase 1b: To identify a safe dose level of AMG 102, up to 15 mg/kg Q3W, to combine with mitoxantrone and prednisone (MP) Phase 2: To estimate with adequate precision the effect of the addition of AMG 102 to MP, compared with placebo plus MP, as assessed by the hazard ratio (HR) for overall survival (OS) of previously treated subjects with castrate-resistant prostate cancer (CRPC)

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the prostate

• Radiographic evidence of metastatic disease

• Progressive disease meeting at least one of the following criteria:

  1. a sequence of at least 2 rising PSA values measured at a minimum of 1 week apart with a 2 ng/mL minimum starting value, or
  2. progression according to RECIST criteria for measurable lesions, or
  3. appearance of 2 or more new lesions on bone scan.

• History of prior taxane-based chemotherapy for metastatic prostate cancer

• For patients without a history of surgical castration, continued GnRH analog administration is required

• ECOG Performance status of 0 or 1

• Life expectancy ≥ 3 months

Exclusion Criteria:

• Treatment with external beam radiotherapy ≤ 14 days before enrollment or radiopharmaceutical ≤8 weeks
• ≤ 4 weeks since receipt of most recent prior chemotherapy, non-GnRH analog hormonal therapy (except for continuing corticosteroids) or other systemic therapy to treat prostate cancer and <6 weeks since receipt of prior bevacizumab.
• Known CNS metastases (epidural disease is allowed if it has been treated and there is no progression in the treated area).
• Significant cardiovascular disease
• LVEF < 50% by MUGA or ECHO
• Treatment of infection with systemic anti-infectives within 7 days before enrollment (with the exception of uncomplicated urinary tract infection)
• Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except that use of low dose coumarin-type anticoagulants or heparins for prophylaxis against central venous catheter thrombosis is allowed
• Major surgical procedure ≤30 days before enrollment or not yet recovered from prior major surgery
• Presence of peripheral edema > Grade 2
• Known positive test for HIV, hepatitis C, chronic or active hepatitis B
• Serious or non-healing wound
• Unable to begin protocol specified treatment within 7 days after enrollment
• Other investigational procedures are excluded.