A Study of Pertuzumab in Participants With Prostate Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of intravenous (IV) pertuzumab in participants with hormone-refractory prostate cancer who have had no previous chemotherapy. Participants will be enrolled in two stages, the first (Cohort A) at a lower 420-mg dose and the second (Cohort B) at a higher 1050-mg dose based upon observations in Cohort A. Up to 50 participants may enter either cohort, for a total enrollment between 46 and 73 participants across 9 study centers.

Official Title
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An Open Label, Phase II, Multicenter Study to Evaluate the Efficacy and Safety of a Recombinant Humanized Antibody to HER2 (Pertuzumab) Administered Every 3 Weeks to Patients With Hormone-Refractory Prostate Cancer Who Have Not Been Treated With Chemotherapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Pertuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults greater than (>) 18 years of age Histologically documented adenocarcinoma of the prostate resistant to hormone therapy, progressed at 4 to 6 weeks following anti-androgen withdrawal Prostate-specific antigen (PSA) values at least 20 ng/mL among those with asymptomatic or mildly symptomatic disease Karnofsky performance status (KPS) at least 80 percent (%) Castrate testosterone less than (<) 50 ng/dL Life expectancy at least 12 weeks Left ventricular ejection fraction (LVEF) at least 50% Adequate hematologic, hepatic, and renal function Exclusion Criteria: Prior chemotherapy, radionucleotide therapy, or immunotherapy for prostate cancer Systemic corticosteroids within 1 month prior to Screening Bisphosphonates within 6 months, narcotic analgesics within 2 weeks, or any investigational agent with 28 days of study drug Prior cumulative doxorubicin dose of > 360 mg/m^2 or equivalent Central nervous system (CNS) or pulmonary metastases Other malignancies, except adequately treated basal or squamous cell skin cancer Significant cardiovascular disease Active/uncontrolled concurrent illness or infection Major surgery or traumatic injury within 4 weeks of study drug

Ages Eligible for Study
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Minimum Age: 19 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pertuzumab 1050 mg (Cohort B)<br>Participants in Cohort B will receive 1050 mg pertuzumab via IV infusion on Day 1 of each 3-week cycle. At the end of 3 treatment cycles, response will be evaluated to determine whether additional participants will be enrolled for treatment. If a second stage of enrollment occurs, participants may continue treatment until disease progression or unacceptable toxicity. | Drug: Pertuzumab<br>* Participants will receive pertuzumab on Day 1 of each 3-week cycle. In Cohort A, an 840-mg loading dose will be administered prior to the 420-mg IV infusion. In Cohort B, the 1050-mg IV infusion will be administered with no loading dose.<br>* Other names: Perjeta;|
| Experimental: Pertuzumab 420 mg (Cohort A)<br>Participants in Cohort A will receive an IV loading dose of 840 milligrams (mg) pertuzumab followed by 420 mg via IV infusion on Day 1 of each 3-week cycle. At the end of 3 treatment cycles, response will be evaluated to determine whether additional participants will be enrolled for treatment. If a second stage of enrollment occurs, participants may continue treatment until disease progression or unacceptable toxicity. | Drug: Pertuzumab<br>* Participants will receive pertuzumab on Day 1 of each 3-week cycle. In Cohort A, an 840-mg loading dose will be administered prior to the 420-mg IV infusion. In Cohort B, the 1050-mg IV infusion will be administered with no loading dose.<br>* Other names: Perjeta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | Objective PSA response rate was determined according to Prostate Specific Antigen Working Group (PSAWG) guidelines. All participants achieving a drop in PSA of greater than or equal to (≥) 50 percent (%) from baseline (confirmed with a second value at least 4 weeks later) fulfilled the criteria of a PSA response. The confirmatory second value had to be at least 50% lower than baseline, but could be higher than the first drop in PSA. Confirmatory value could not be 50% higher compared to first drop in PSA. The date of response was the date the first 50% (or greater) decline was observed. Progressive disease (PD) was defined by a minimum of three consecutive serum PSA measurements obtained at least 7 days apart within the previous 3 months of start of trial, which documented progressively increasing values. Non-response was defined as neither PD nor Response. | Screening, Every 3 weeks up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Time to disease progression was defined by time in weeks from start of therapy to the onset of the earliest of the following events. 1) PSA progression as defined by the PSAWG, 2) Evidence of disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 3) One bone scan at least 6 months subsequent to baseline demonstrating 2 or more new skeletal lesions and 4) An event due to metastatic prostate cancer requiring intervention. | Screening, Every 3 weeks up to a maximum of 18 months | 
| Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Overall objective response by RECIST criteria (CR or PR) was to be defined for participants who had measurable disease at baseline or developed new lesions post-baseline. The longest diameter only for all target lesions was measured and the following responses recorded: CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter as compared to the baseline sum longest diameter. | Screening, Weeks 6, 12, 24, 36 and 48 | 
| Time to Response | Time to response was the date of the first documentation of PSA response. | Screening, Every 3 weeks for a maximum of 18 months | 
| Duration of Response According to PSA Levels | Duration of PSA Response was measured from first 50% decline in PSA compared to baseline until the time at which there was an increase of ≥50% from the PSA nadir, provided the absolute increase was at least 5 nanograms per milliliter (ng/ml). The increase must have been confirmed by a second consecutive measurement that was at least 50% above the nadir. | Baseline, Every 3 weeks for a maximum of 18 months | 
| Duration of Response According to RECIST Criteria | For participants with measurable disease, duration of response was defined as first documentation of tumor response, either a PR or CR, to first documentation of PD or death. Participants who never progressed or died were censored at their last tumor measurement. | Baseline, Weeks 6, 12, 24, 36 and 48 | 
| Percentage of Participants Without Progression | Disease progression was defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Non-progression included participants who had responded plus those who had not responded and not progressed within the first 3 cycles. | Screening, Weeks 3, 6, 9 and 12 | 
| Time to Prostate Cancer Pain Progression | Time to disease progression was defined by time in weeks from start of therapy to the onset of the earliest of the following events: 1) Opioid therapy, 2) Radiation therapy, 3) Glucocorticoid therapy, 4) Radionuclide therapy or 5) Chemotherapy. | Every 3 weeks up to a maximum of 18 weeks | 
| Overall Survival | Overall survival was defined as the interval of time in weeks between start of treatment and day of death. Participants who did not die while being followed were censored at the last time that they were known to be alive. | Screening, Every 3 weeks up to a maximum of 18 months | 
| Time to Treatment Failure | Time to Treatment Failure was time to the first documentation of progressive disease, day of death while on study (or 30 days after withdrawing from the trial) or day of early discontinuation due to toxicity (adverse events or abnormal laboratory value), refusal of treatment/refusing to cooperate/withdrawing consent, insufficient therapeutic response, or failure to return, whichever is earliest, after the start of treatment. Participants who did not experience any of the above events while on study were censored on the day of their last PSA or tumor measurement, whichever was later. | Every 3 weeks up to a maximum of 18 weeks | 
| Change From Baseline in Bone Alkaline Phosphatase | Bone alkaline phosphatase (BAP) is the bone-specific isoform of alkaline phosphatase. Serum Bone alkaline phosphatase is used to measure osteoporosis and is measured as units per liter (u/L). | Screening, Weeks 6, 12, 24, 36 and 48 | 
| Change From Baseline in N-Telopeptide | In bone physiology, the N-terminal telopeptide (or more formally, amino-terminal collagen crosslinks, and known by the acronym NTX) is a telopeptide that can be used as a biomarker to measure the rate of bone turnover. NTX can be measured in the urine (uNTX) or serum (serum NTX). | Screening, Weeks 6, 12, 24, 36 and 48 | 
| Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (µg*day/mL) | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab | The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| Maximum Plasma Concentration of Pertuzumab | Cmax is the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and prior to the administration of a second dose. Cmax is measured as micrograms per mL (μg/mL). | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| Time to Maximum Plasma Concentration (Tmax) of Pertuzumab | Cmax refers to the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and prior to the administration of a second dose. tmax is the time at which the Cmax is observed. | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1 and on Days 8 and 15, Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| Terminal Elimination Half-Life (t1/2) of Pertuzumab | t1/2 is the time in days required for the concentration of the drug to reach half of its original value | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| Serum Clearance of Pertuzumab | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day). | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| Volume of Distribution at Steady State of Pertuzumab | The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 | 
| Mean Residence Time (MRT) of Pertuzumab | MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days. | Cycles 1 and 2 (Weeks 3 and 6): predose (immediately prior to infusion) and within 15 minutes following the end of the infusion on Day 1, Day 8, and Day 15. Cycle 3 (Week 9) and beyond: predose and within 15 minutes following end of infusion on Day 1 |