Inclusion Criteria:

• Signed informed consent
• Age >= 18 years old
• Histologically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as assessed by progression following at least one hormonal therapy (orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonist). Subjects must have documented progression following hormonal therapy withdrawal of >= 4 weeks duration; nilutamide and bicalutamide require 6 weeks withdrawal.
• Progression of disease after one prior chemotherapy regimen (which must have been taxane-based) for CRPC. Progression is defined as at least one of the following: A minimum of three consecutive serum PSA measurements obtained >= 14 days apart and all within 3 months, with progressively increasing values for two consecutive measurements. The latest value must be obtained within the screening period and must be >= 5 ng/mL; or progression of measurable disease, as defined by RECIST; or progression of bone disease, as defined by the appearance of one or more new bone lesions
• Orchiectomy, or castrate levels of testosterone maintained by LHRH agonist <70 ng/mL
• Life expectancy >= 12 weeks
• ECOG performance status of 0 or 1
• Granulocyte count of >= 1500/mL, platelet count of >= 75,000/mL and hemoglobin of >= 9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin [Aranesp] is permitted)
• Serum bilirubin less than or equal to the upper limit of normal (ULN), unless due to Gilbert's disease, and alkaline phosphatase, AST, and ALT <= 2.5 x ULN (ALT, AST, and alkaline phosphatase <= 5 x ULN for subjects with liver metastases; no alkaline phosphatase upper limit for subjects with bone metastases)
• Serum creatinine <= 1.5 x ULN
• International normalized ratio (INR) <1.5 and activated partial thromboplastin time (aPTT) <1.5 x ULN (except for subjects receiving warfarin)
• Willing to complete serial PROSQOLI/PPI evaluations and serial diaries of analgesic use (if necessary)

Exclusion Criteria:

• Prior chemotherapy, radiotherapy, therapeutic radionucleotide or immunotherapy within 4 weeks of Day 1 (the day of the first rhuMAb 2C4 dose). Flutamide therapy, or other second line hormonal therapies should be withdrawn >= 4 weeks prior to Day 1. Bicalutamide and nilutamide therapy should be withdrawn >= 6 weeks prior to starting study medication.
• Prior treatment with HER2 pathway inhibitors (e.g., Herceptin [Trastuzumab], Iressa [gefitinib], Tarceva [erlotinib hydrochloride], C225, CI1033, and TAK165)
• Treatment with other experimental anticancer agents within 4 weeks prior to Day 1
• Prior history or clinical evidence of central nervous system or brain metastases
• Ejection fraction, determined by ECHO, <50%
• Uncontrolled hypercalcemia (>11.5 mg/dL)
• Prior exposure of >360 mg/m2 doxorubicin, >120 mg/m2 mitoxantrone, or >90 mg/m2 idarubicin
• Ongoing corticosteroid treatment, except for subjects who are on stable doses of <20 mg of prednisone daily (or equivalent), or who are taking corticosteroids for reasons unrelated to prostate cancer
• History of other malignancies within 5 years prior to Day 1, except for adequately treated basal or squamous cell skin cancer
• History of serious systemic disease, including active infection, uncontrolled hypertension (diastolic blood pressure >100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible)
• Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus infection
• Major surgery or significant traumatic injury within 3 weeks prior to Day 1
• Inability to comply with study and follow-up procedures
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk for treatment complications