Clinical trial NCT00058539: Safety and Efficacy Study of Pertuzumab to Treat Castration-Resistant Prostate Cancer
Official title: A Phase II, Open-Label, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Omnitarg (Pertuzumab) in Subjects With Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2003-04-09
Enrollment: 42
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: 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
timeFrame: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab
measure: Kaplan Meier Estimate of Percentage of Participants With Disease Progression at 3 Months
timeFrame: 3 months
Secondary outcomes:
measure: Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS])
timeFrame: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab
measure: Median Time of PFS
timeFrame: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab
measure: Duration of Response
timeFrame: Screening, Day 1 of Cycles 1-17, and at 30 days after the last dose of pertuzumab
measure: Percentage of Participants Who Progressed at 3, 6 and 9 Months
timeFrame: 3, 6, and 9 months
measure: Serum Concentrations of Pertuzumab
timeFrame: 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
Other outcomes:
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