Phase 3 Study of Immunotherapy to Treat Advanced Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine if asymptomatic or minimally symptomatic patients with metastatic prostate cancer who have not received chemotherapy live longer when treated with ipilimumab than those treated with a placebo

Official Title
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Randomized, Double-Blind, Phase 3 Trial to Compare the Efficacy of Ipilimumab vs Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naïve Castration Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Ipilimumab
* Drug: Placebo


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: Metastatic prostate cancer Asymptomatic or minimally symptomatic Progression during hormonal therapy Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Exclusion Criteria: Liver, lung or brain metastases Prior immunotherapy or chemotherapy for metastatic prostate cancer Autoimmune disease HIV, Hepatitis B, or Hepatitis C infection

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: Ipilimumab<br> | Drug: Ipilimumab<br>* 5 mg/ml solution, Intravenous, 10 mg/kg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase. Up to 24 weeks in the Induction Phase. Treatment in the Maintenance Phase continues until total treatment period has reached three years,Treatment Stopping Criteria are met, withdrawal of consent, or study closure<br>* Other names: MDX010;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Solution, Intravenous, 0 mg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase. Up to 24 weeks in the Induction Phase. Treatment in the Maintenance Phase continues until total treatment period has reached three years,Treatment Stopping Criteria are met, withdrawal of consent, or study closure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Time | OS was defined as the time from the date of randomization until the date of death. For participants without documentation of death, OS was censored at the last date the participant was known to be alive. | Randomization until death from any cause, up to April 2015, approximately 57 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Time | Progression-free survival, as determined by the investigator, was defined as the time from randomization to the earliest date of confirmed Prostate-Specific Antigen (PSA) progression, confirmed radiological progression, clinical deterioration, or death. | Randomization until disease progression, up to April 2015, approximately 57 months | 
| Time to Subsequent Non-hormonal Cytotoxic Therapy | For participants who discontinued treatment or experienced disease progression while on study therapy and then received subsequent non-hormonal cytotoxic therapy, time to subsequent non-hormonal cytotoxic therapy was defined as the time from randomization to the time of initiation of subsequent non-hormonal cytotoxic therapy. Participants who did not receive subsequent non-hormonal cytotoxic therapy were censored on the last known alive date (for participants who have not died) or the date of last follow-up contact at which the participants was known alive (for participants who died). | Randomization until subsequent non-hormonal cytotoxic therapy, up to April 2015, approximately 57 months | 
| Time to Pain Progression | Time to pain progression was defined as the time from randomization to the time of the earliest date of any of the following 4 events: 1) an increase in average daily worst pain intensity of >= 2 points from baseline according to the Brief Pain Inventory - Short Form (BPI-SF), maintained over 2 consecutive time periods. 2) initiation of opioid analgesic (excluding codeine or dextropropoxyphene). 3) initiation of palliative radiotherapy for prostate cancer. 4) increase in mean Analgesic Score (AS) of >= 25% from baseline (for participants with baseline AS > 10) or increase in mean AS >= 10 points from baseline (for participants with baseline AS <= 10). Participants who did not experience any of these events were censored on the earliest date among the latest BPI-SF completion date with non-missing worst pain assessment and last evaluable disease assessment date as defined in the PFS censoring mechanism. | Randomization until pain progression, up to April 2015, approximately 57 months | 
| Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. irAE=AEs consistent with an immune mediated mechanism. imAR=AEs of special interest that were adjudicated as imAR by investigator. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. | Day 1 of study therapy to last dose plus 70 days | 
| Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities | NCI CTC, Version 3 used to assess parameters. LLN=lower limit of normal. ULN=upper limit of normal. CTC criteria: White blood cells (WBC): Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. Absolute neutrophil count (ANC): Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count: Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin: Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Absolute Lymphocyte Count (ALC): Gr 3: 0.2 - <0.5*10^9/L, Gr 4: <0.2*10^9/L. Lipase: Gr 3:> 2.0 - 5.0 * ULN; Gr 4: > 5.0 X ULN. Amylase: Gr 3: > 2.0 - 5.0 * ULN; Gr 4: > 5.0 * ULN. Alanine Aminotransferase (ALT) Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Aspartate Aminotransferase (AST): Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Bilirubin: Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN. Alkaline Phosphatase: Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Creatinine: Gr 3: > 3.0-6.0 * ULN, Gr 4: >6.0 * ULN. | Randomization up to April 2015, approximately 57 months |