Prostate Cancer
Conditions
Brief summary
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.
Interventions
DRUGPertuzumab
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | Screening, Every 3 weeks up to Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Screening, Weeks 6, 12, 24, 36 and 48 | 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. |
| Time to Response | Screening, Every 3 weeks for a maximum of 18 months | Time to response was the date of the first documentation of PSA response. |
| Duration of Response According to PSA Levels | Baseline, Every 3 weeks for a maximum of 18 months | 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. |
| Duration of Response According to RECIST Criteria | Baseline, Weeks 6, 12, 24, 36 and 48 | 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. |
| Percentage of Participants Without Progression | Screening, Weeks 3, 6, 9 and 12 | 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. |
| Time to Prostate Cancer Pain Progression | Every 3 weeks up to a maximum of 18 weeks | 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. |
| Overall Survival | Screening, Every 3 weeks up to a maximum of 18 months | 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. |
| Time to Treatment Failure | Every 3 weeks up to a maximum of 18 weeks | 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. |
| Change From Baseline in Bone Alkaline Phosphatase | Screening, Weeks 6, 12, 24, 36 and 48 | 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). |
| Time to Disease Progression | Screening, Every 3 weeks up to a maximum of 18 months | 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. |
| Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab | 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 | 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) |
| AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab | 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 | 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. |
| Maximum Plasma Concentration of Pertuzumab | 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 | 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). |
| Time to Maximum Plasma Concentration (Tmax) of Pertuzumab | 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 | 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. |
| Terminal Elimination Half-Life (t1/2) of Pertuzumab | 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 | t1/2 is the time in days required for the concentration of the drug to reach half of its original value |
| Serum Clearance of Pertuzumab | 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 | 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). |
| Volume of Distribution at Steady State of Pertuzumab | 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 | 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. |
| Mean Residence Time (MRT) of Pertuzumab | 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 | MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days. |
| Change From Baseline in N-Telopeptide | Screening, Weeks 6, 12, 24, 36 and 48 | 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). |
Countries
France, Germany, Italy, Netherlands, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pertuzumab 420 mg - Cohort A Participants in Cohort A received an IV loading dose of 840 mg pertuzumab on Day 1 of Cycle 1 (3-week cycles); from Cycle 2 onwards, participants received IV infusions of 420 mg on Day 1. Treatment continued for a maximum of 36 cycles or until study termination. | 35 |
| Pertuzumab 1050 mg - Cohort B Participants in Cohort B received 1050 mg pertuzumab as an IV infusion on Day 1 of each 3-week cycle for a maximum of 36 cycles or until study termination. | 33 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Insufficient therapeutic response | 31 | 29 |
| Overall Study | Refused Treatment | 0 | 3 |
Baseline characteristics
| Characteristic | Pertuzumab 420 mg - Cohort A | Pertuzumab 1050 mg - Cohort B | Total |
|---|---|---|---|
| Age, Continuous | 70.8 years STANDARD_DEVIATION 7.45 | 71.2 years STANDARD_DEVIATION 6.01 | 71.0 years STANDARD_DEVIATION 6.74 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 33 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 35 | 24 / 33 |
| serious Total, serious adverse events | 9 / 35 | 6 / 33 |
Outcome results
Primary
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.
Time frame: Screening, Every 3 weeks up to Week 24
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | 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 response | 0.0 percentage of participants |
| Pertuzumab 420 mg - Cohort A | Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | Non-response | 34.3 percentage of participants |
| Pertuzumab 420 mg - Cohort A | Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | Missing | 0.0 percentage of participants |
| Pertuzumab 420 mg - Cohort A | Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | PD | 65.7 percentage of participants |
| Pertuzumab 1050 mg - Cohort B | Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | Missing | 3.0 percentage of participants |
| Pertuzumab 1050 mg - Cohort B | 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 response | 0.0 percentage of participants |
| Pertuzumab 1050 mg - Cohort B | Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | Non-response | 30.3 percentage of participants |
| Pertuzumab 1050 mg - Cohort B | Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab | PD | 66.7 percentage of participants |
Secondary
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)
Time frame: 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
Population: ITT Population; Only participants with non-missing data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab | 3488 µg*day/mL | Geometric Coefficient of Variation 44 |
| Pertuzumab 1050 mg - Cohort B | Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab | 5097 µg*day/mL | Geometric Coefficient of Variation 71 |
Secondary
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.
Time frame: 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
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab | 2305 µg*day/mL | Geometric Coefficient of Variation 22 |
| Pertuzumab 1050 mg - Cohort B | AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab | 2626 µg*day/mL | Geometric Coefficient of Variation 28 |
Secondary
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).
Time frame: Screening, Weeks 6, 12, 24, 36 and 48
Population: Data were not analyzed to due to early termination of the study.
Secondary
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).
Time frame: Screening, Weeks 6, 12, 24, 36 and 48
Population: Data were not analyzed to due to early termination of the study.
Secondary
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.
Time frame: Baseline, Every 3 weeks for a maximum of 18 months
Population: This analysis was only planned if either cohort went to full recruitment. Analysis of this outcome in a small number of participants would have high variability and also unlikely to be relevant if safety and tolerability criteria were not met.
Secondary
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.
Time frame: Baseline, Weeks 6, 12, 24, 36 and 48
Population: This analysis was only planned if either cohort went to full recruitment. Analysis of this outcome in a small number of participants would have high variability and also unlikely to be relevant if safety and tolerability criteria were not met.
Secondary
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).
Time frame: 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
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Maximum Plasma Concentration of Pertuzumab | 255 μg/mL | Geometric Coefficient of Variation 23 |
| Pertuzumab 1050 mg - Cohort B | Maximum Plasma Concentration of Pertuzumab | 294 μg/mL | Geometric Coefficient of Variation 24 |
Secondary
Mean Residence Time (MRT) of Pertuzumab
MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days.
Time frame: 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
Population: ITT Population; Only participants with non-missing data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Mean Residence Time (MRT) of Pertuzumab | 18.1 days | Geometric Coefficient of Variation 42 |
| Pertuzumab 1050 mg - Cohort B | Mean Residence Time (MRT) of Pertuzumab | 25.7 days | Geometric Coefficient of Variation 77 |
Secondary
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.
Time frame: Screening, Every 3 weeks up to a maximum of 18 months
Population: Data were not analyzed due to early termination of the study.
Secondary
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.
Time frame: Screening, Weeks 6, 12, 24, 36 and 48
Population: This analysis was only planned if either cohort went to full recruitment. Analysis of this outcome in a small number of participants would have high variability and also unlikely to be relevant if safety and tolerability criteria were not met.
Secondary
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.
Time frame: Screening, Weeks 3, 6, 9 and 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab 420 mg - Cohort A | Percentage of Participants Without Progression | 20.0 percentage of participants |
| Pertuzumab 1050 mg - Cohort B | Percentage of Participants Without Progression | 18.2 percentage of participants |
Secondary
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).
Time frame: 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
Population: ITT Population; Only participants with non-missing data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Serum Clearance of Pertuzumab | 270 mL/day | Geometric Coefficient of Variation 29 |
| Pertuzumab 1050 mg - Cohort B | Serum Clearance of Pertuzumab | 253 mL/day | Geometric Coefficient of Variation 35 |
Secondary
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
Time frame: 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
Population: ITT Population; Only participants with non-missing data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Terminal Elimination Half-Life (t1/2) of Pertuzumab | 13.7 days | Geometric Coefficient of Variation 39 |
| Pertuzumab 1050 mg - Cohort B | Terminal Elimination Half-Life (t1/2) of Pertuzumab | 19.3 days | Geometric Coefficient of Variation 69 |
Secondary
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.
Time frame: Screening, Every 3 weeks up to a maximum of 18 months
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab 420 mg - Cohort A | Time to Disease Progression | 5.6 weeks |
| Pertuzumab 1050 mg - Cohort B | Time to Disease Progression | 6.1 weeks |
Secondary
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.
Time frame: 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
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Time to Maximum Plasma Concentration (Tmax) of Pertuzumab | 0.073 days | Geometric Coefficient of Variation 11 |
| Pertuzumab 1050 mg - Cohort B | Time to Maximum Plasma Concentration (Tmax) of Pertuzumab | 0.074 days | Geometric Coefficient of Variation 6 |
Secondary
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.
Time frame: Every 3 weeks up to a maximum of 18 weeks
Population: This analysis was only planned if either cohort went to full recruitment. Analysis of this outcome in a small number of participants would have high variability and also unlikely to be relevant if safety and tolerability criteria were not met.
Secondary
Time to Response
Time to response was the date of the first documentation of PSA response.
Time frame: Screening, Every 3 weeks for a maximum of 18 months
Population: This analysis was only planned if either cohort went to full recruitment. Analysis of this outcome in a small number of participants would have high variability and also unlikely to be relevant if safety and tolerability criteria were not met.
Secondary
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.
Time frame: Every 3 weeks up to a maximum of 18 weeks
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab 420 mg - Cohort A | Time to Treatment Failure | 6.1 days |
| Pertuzumab 1050 mg - Cohort B | Time to Treatment Failure | 6.1 days |
Secondary
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.
Time frame: 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
Population: ITT Population; Only participants with non-missing data were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pertuzumab 420 mg - Cohort A | Volume of Distribution at Steady State of Pertuzumab | 4452 mL | Geometric Coefficient of Variation 26 |
| Pertuzumab 1050 mg - Cohort B | Volume of Distribution at Steady State of Pertuzumab | 5227 mL | Geometric Coefficient of Variation 24 |