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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Open-Label, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Omnitarg (Pertuzumab) in Subjects With Castration-Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: rhuMAb 2C4 (pertuzumab)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: rhuMAb 2C4 (pertuzumab)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Overall Confirmed Response of Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) and Prostate Specific Antigen (PSA) Response Rate Based on Bubley Criteria | Response by tumor measurement occurred if there was documented and confirmed CR or PR. Response was assessed by both the RECIST and by PSA levels measurement, based on measurable or non-measurable disease at baseline. Per RECIST, CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A PSA response was defined as a PSA decline of greater than or equal to (≥) 50%, which had to be confirmed by a second PSA value at least 4 weeks later. | Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab | 
| Kaplan Meier Estimate of Percentage of Participants With Disease Progression at 3 Months | Per RECIST, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of 1 or more new lesions, and/or unequivocal progression of existing non-target lesions. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS]) | PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment. The percentage of participants experiencing disease progression or death was calculated as the number of participants with an event divided by the number of participants analyzed, multiplied by 100. | Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab | 
| Median Time of PFS | PFS was defined as the time from the first day of study drug treatment to the time of documented disease progression or death, whichever came first. Participants who were lost to follow-up or who had not progressed at the time of study completion or early termination were censored at the date of last tumor assessment. | Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab | 
| Duration of Response | Duration of response was defined as the time from the initial CR or PR to the time of disease progression. | Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab | 
| Percentage of Participants Who Progressed at 3, 6 and 9 Months | Per RECIST, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of 1 or more new lesions, and/or unequivocal progression of existing non-target lesions. Percentage of participants who were free from disease progression was calculated by subtracting the number of participants with disease progression at that time point from the total population at risk of disease progression, multiplied by 100. | 3, 6, and 9 months | 
| Serum Concentrations of Pertuzumab |  | Assessed at pre-dose, 15-minutes postdose on Day 1 (Cycle 1), Day 22 (Cycle 2), Day 43 (Cycle 3), Day 85 (Cycle 5), and Day 169 (Cycle 9); pre-dose on Day 253 (Cycle 13), and on Days 8, 15, 29 and 36 |