Back to resultsA Study of Pertuzumab in Participants With Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pertuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Pertuzumab 1050 mg (Cohort B)
Pertuzumab 420 mg (Cohort A)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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 to Response
Time to response was the date of the first documentation of PSA response.
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.
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.
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 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.
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 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.
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).
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).
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)
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.
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 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.
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
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).
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.
Mean Residence Time (MRT) of Pertuzumab
MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02480010
Brief Title
A Study of Pertuzumab in Participants With Prostate Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2015
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated at the time of interim analysis since none of the participants showed a PSA response.
Study Start Date
September 2003 (undefined)
Primary Completion Date
September 2005 (Actual)
Study Completion Date
September 2005 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pertuzumab 1050 mg (Cohort B)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pertuzumab 420 mg (Cohort A)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Other Intervention Name(s)
Perjeta
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Confirmed, Objective Response, Non-Response or Progressive Disease by PSA Levels Within the First 24 Weeks of Treatment With Pertuzumab
Description
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
Secondary Outcome Measure Information:
Title
Time to Disease Progression
Description
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
Title
Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Description
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
Title
Time to Response
Description
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
Title
Duration of Response According to PSA Levels
Description
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
Title
Duration of Response According to RECIST Criteria
Description
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
Title
Percentage of Participants Without Progression
Description
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
Title
Time to Prostate Cancer Pain Progression
Description
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
Title
Overall Survival
Description
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
Title
Time to Treatment Failure
Description
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
Title
Change From Baseline in Bone Alkaline Phosphatase
Description
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
Title
Change From Baseline in N-Telopeptide
Description
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
Title
Area Under the Concentration Curve Extrapolated to Infinity (AUC0-Inf) of Pertuzumab
Description
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
Title
AUC to Last Measurable Concentration (AUC0-last) of Pertuzumab
Description
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
Title
Maximum Plasma Concentration of Pertuzumab
Description
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
Title
Time to Maximum Plasma Concentration (Tmax) of Pertuzumab
Description
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
Title
Terminal Elimination Half-Life (t1/2) of Pertuzumab
Description
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
Title
Serum Clearance of Pertuzumab
Description
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
Title
Volume of Distribution at Steady State of Pertuzumab
Description
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
Title
Mean Residence Time (MRT) of Pertuzumab
Description
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
City
Lyon
ZIP/Postal Code
69008
Country
France
City
Montpellier
ZIP/Postal Code
34298
Country
France
City
Berlin
ZIP/Postal Code
12203
Country
Germany
City
Parma
ZIP/Postal Code
43100
Country
Italy
City
Roma
ZIP/Postal Code
00152
Country
Italy
City
Rotterdam
ZIP/Postal Code
3075 EA
Country
Netherlands
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Valencia
ZIP/Postal Code
46009
Country
Spain
City
Cardiff
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
City
Weston Super Mare
ZIP/Postal Code
BS23 4TQ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Pertuzumab in Participants With Prostate Cancer
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