Inclusion Criteria:

• The patient has histologically-confirmed adenocarcinoma of the prostate
• The patient has radiographic evidence of metastatic prostate cancer (stage M1 or D2)
• The patient has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)
• The patient has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

• The patient must have evidence of progressive disease defined as at least one of the following;

  1. Progressive measurable disease: using conventional solid tumor criteria
  2. Bone scan progression: at least two new lesions on bone scan
  3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2
• The patient has a PSA ≥ 2 ng/mL
• The patient has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the patient must be willing to continue the use of LHRH agonists during protocol treatment
• The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
• The patient has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)
• The patient has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN)], aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)
• The patient has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)
• The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
• The patient has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Patients receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)
• The patient has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

• The patient has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Patients who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)
• The patient has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)
• The patient has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN
• The patient has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab
• The patient is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Patients receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration
• The patient has known or suspected brain or leptomeningeal metastases
• The patient has uncontrolled or poorly controlled hypertension
• The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
• The patient has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness