Safety and Efficacy Study of Ipilimumab 3 mg/kg Versus Ipilimumab 10 mg/kg in Subjects With Metastatic Castration Resistant Prostate Cancer Who Are Chemotherapy Naive

Study Overview
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Brief Summary
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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
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Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Response Evaluation Criteria In Solid Tumors (RECIST)

Official Title
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A Phase 2, Randomized, Double-Blind Study of Ipilimumab Administered at 3 mg/kg vs 10 mg/kg in Adult Subjects With Metastatic Chemotherapy-Naïve Castration Resistant Prostate Cancer Who Are Asymptomatic or Minimally Symptomatic

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Ipilimumab 3 mg/kg<br>Ipilimumab 3 mg/kg injection intravenously every 3 weeks for 4 doses in Induction phase. Subjects that are eligible to receive Ipilimumab in the Maintenance phase will be dosed every 12 weeks for a maximum of 3 years since the first induction dose | Drug: Ipilimumab<br> <br> * Other names: Yervoy™;|
| Experimental: Arm 2: Ipilimumab 10 mg/kg<br>Ipilimumab 10 mg/kg injection intravenously every 3 weeks for 4 doses in Induction phase. Subjects that are eligible to receive Ipilimumab in the Maintenance phase will be dosed every 12 weeks for a maximum of 3 years since the first induction dose | Drug: Ipilimumab<br> <br> * Other names: Yervoy™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From date of randomization until disease progression or death (assessed up to December 2016, approximately 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From first dose of ipilimumab to last dose plus 90 days | 
| 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. | From randomization to death from any cause (assessed up to December 2016, approximately 24 months) | 
| 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. | From randomization to the earliest date of PSA progression or death, whichever comes earlier (assessed up to December 2016, approximately 24 months) | 
| 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. | From randomization until pain progression (assessed up to December 2016, approximately 24 months) | 
| 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. | From baseline to PSA response (assessed up to December 2016, approximately 48 months) |