Safety and Efficacy Study of Pertuzumab to Treat Castration-Resistant Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: rhuMAb 2C4 (pertuzumab)
Intervention MeSH terms: Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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