Prostate Cancer
Conditions
Brief summary
The purpose of this study is to examine the safety and effectiveness (how well the drug works) of two different doses (3 mg/kg and 10 mg/kg) of Ipilimumab (Yervoy™) in patients with metastatic castration resistant prostate cancer.
Detailed description
Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Response Evaluation Criteria In Solid Tumors (RECIST)
Interventions
DRUGIpilimumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Prostate cancer with metastases * Prostate cancer should be castration resistant * Progression during hormonal therapy
Exclusion criteria
* Visceral metastases (eg liver, lung or brain metastases) * Prior treatment with any immunotherapy for prostate cancer * Prior or ongoing cytotoxic therapy for prostate cancer * Autoimmune disease * Inadequate hematologic, renal, or hepatic function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-free Survival (rPFS) | From date of randomization until disease progression or death (assessed up to December 2016, approximately 24 months) | rPFS was defined as the time from the date of randomization until the date of disease progression based on radiographic evidence and/or death from any cause, whichever occurs first. Radiographic disease progression is defined as: Confirmed bone disease progression according to criteria adapted from the Prostate Cancer Clinical Trials Working Group 2 (PCWG2), OR Non-bone disease progression according to the modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The number of participants with reported radiographic progression is shown. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Immune-related Adverse Events (irAEs) | From first dose of ipilimumab to last dose plus 90 days | The total number of participants with immune-related adverse events of any grade is reported for each arm. |
| Overall Survival (OS) | From randomization to death from any cause (assessed up to December 2016, approximately 24 months) | OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored at the last date the participant was known to be alive. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The total number of reported deaths is shown. |
| Prostate Specific Antigen Progression-free Survival (PSA PFS) | From randomization to the earliest date of PSA progression or death, whichever comes earlier (assessed up to December 2016, approximately 24 months) | Prostate specific antigen progression-free survival (PSA PFS) was defined as the time from randomization to the earliest date of PSA progression or death, whichever occurs earlier. Participants who did not progress or die were censored at the last PSA assessment date. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The number of participants with reported PSA progression is shown. |
| Time to Pain Progression | From randomization until pain progression (assessed up to December 2016, approximately 24 months) | Pain progression was defined as an increase in BPI-SF pain Item #3 score of \>= 2 point from baseline maintained over 2 consecutive periods. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment, and presented efficacy results are based on limited data. The number of participants with reported pain progression is shown. |
| Prostate Specific Antigen Response Rate | From baseline to PSA response (assessed up to December 2016, approximately 48 months) | PSA response rate was defined as the proportion of participants with a 50% or greater decrease from baseline to the lowest post-baseline PSA result (confirmed 3 weeks later) for each randomized arm. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The number of participants showing PSA response is shown. |
Countries
Australia, Chile, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
82 participants were enrolled; 53 were randomized; 51 were treated with study drug. 29 were not randomized due to screening failures. 2 were randomized and not treated due to administrative reason by sponsor and other reason
Participants by arm
| Arm | Count |
|---|---|
| Ipilimumab 3 mg/kg Ipilimumab at 3 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | 25 |
| Ipilimumab 10 mg/kg Ipilimumab at 10 mg/kg was administered by intravenous (IV) infusion over a time period of 60-100 minutes, based on body weight. Induction Phase dosing consisted of a single dose every 3 weeks (Q3W) for 4 doses. This was followed by Maintenance Phase dosing of a single dose every 12 weeks (Q12W). Treatment was for a maximum treatment period of 3 years from the first induction dose of blinded study therapy, or until subject met treatment stopping criteria. | 26 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 0 | 1 |
| Overall Study | Disease progression | 5 | 2 |
| Overall Study | No longer meets criteria | 0 | 1 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Study closed by sponsor | 16 | 13 |
| Overall Study | Study drug toxicity | 3 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Ipilimumab 10 mg/kg | Ipilimumab 3 mg/kg |
|---|---|---|---|
| Age, Continuous | 66.00 years FULL_RANGE 9.08 | 66.50 years FULL_RANGE 9.98 | 66.00 years FULL_RANGE 8.23 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 49 Participants | 24 Participants | 25 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 51 Participants | 26 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 26 | 22 / 25 |
| serious Total, serious adverse events | 15 / 26 | 6 / 25 |
Outcome results
Primary
Radiographic Progression-free Survival (rPFS)
rPFS was defined as the time from the date of randomization until the date of disease progression based on radiographic evidence and/or death from any cause, whichever occurs first. Radiographic disease progression is defined as: Confirmed bone disease progression according to criteria adapted from the Prostate Cancer Clinical Trials Working Group 2 (PCWG2), OR Non-bone disease progression according to the modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The number of participants with reported radiographic progression is shown.
Time frame: From date of randomization until disease progression or death (assessed up to December 2016, approximately 24 months)
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ipilimumab 3 mg/kg | Radiographic Progression-free Survival (rPFS) | 4 Participants |
| Ipilimumab 10 mg/kg | Radiographic Progression-free Survival (rPFS) | 3 Participants |
Secondary
Number of Participants Who Experienced Immune-related Adverse Events (irAEs)
The total number of participants with immune-related adverse events of any grade is reported for each arm.
Time frame: From first dose of ipilimumab to last dose plus 90 days
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ipilimumab 3 mg/kg | Number of Participants Who Experienced Immune-related Adverse Events (irAEs) | 13 Participants |
| Ipilimumab 10 mg/kg | Number of Participants Who Experienced Immune-related Adverse Events (irAEs) | 18 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored at the last date the participant was known to be alive. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The total number of reported deaths is shown.
Time frame: From randomization to death from any cause (assessed up to December 2016, approximately 24 months)
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ipilimumab 3 mg/kg | Overall Survival (OS) | 4 Participants |
| Ipilimumab 10 mg/kg | Overall Survival (OS) | 6 Participants |
Secondary
Prostate Specific Antigen Progression-free Survival (PSA PFS)
Prostate specific antigen progression-free survival (PSA PFS) was defined as the time from randomization to the earliest date of PSA progression or death, whichever occurs earlier. Participants who did not progress or die were censored at the last PSA assessment date. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The number of participants with reported PSA progression is shown.
Time frame: From randomization to the earliest date of PSA progression or death, whichever comes earlier (assessed up to December 2016, approximately 24 months)
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ipilimumab 3 mg/kg | Prostate Specific Antigen Progression-free Survival (PSA PFS) | 4 Participants |
| Ipilimumab 10 mg/kg | Prostate Specific Antigen Progression-free Survival (PSA PFS) | 3 Participants |
Secondary
Prostate Specific Antigen Response Rate
PSA response rate was defined as the proportion of participants with a 50% or greater decrease from baseline to the lowest post-baseline PSA result (confirmed 3 weeks later) for each randomized arm. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment. As a result, the presented efficacy results are based on limited data. The number of participants showing PSA response is shown.
Time frame: From baseline to PSA response (assessed up to December 2016, approximately 48 months)
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ipilimumab 3 mg/kg | Prostate Specific Antigen Response Rate | 0 Participants |
| Ipilimumab 10 mg/kg | Prostate Specific Antigen Response Rate | 1 Participants |
Secondary
Time to Pain Progression
Pain progression was defined as an increase in BPI-SF pain Item #3 score of \>= 2 point from baseline maintained over 2 consecutive periods. After termination of the study, collection of tumor assessments and other data to support the efficacy analyses was no longer required in patients who discontinued study treatment, and presented efficacy results are based on limited data. The number of participants with reported pain progression is shown.
Time frame: From randomization until pain progression (assessed up to December 2016, approximately 24 months)
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ipilimumab 3 mg/kg | Time to Pain Progression | 0 Participants |
| Ipilimumab 10 mg/kg | Time to Pain Progression | 1 Participants |