Safety and Efficacy Study of Pertuzumab to Treat Castration-Resistant Prostate Cancer

The purpose of this study is to evaluate safety and efficacy of Omnitarg (Pertuzumab) on cancerous lesions in men with castration-resistant (hormone-refractory) prostate cancer.


Eligibility Criteria:
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