A Study of Nivolumab or Placebo in Combination With Docetaxel in Men With Advanced Castration-resistant Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and effectiveness of nivolumab with docetaxel in men with advanced castration resistant prostate cancer who have progressed after second-generation hormonal manipulation.

Official Title
-----------------
A Phase 3, Randomized, Double-Blind Study of Nivolumab or Placebo in Combination With Docetaxel, in Men With Metastatic Castration-resistant Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Biological: Nivolumab
* Drug: Prednisone
* Drug: Docetaxel
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic confirmation of adenocarcinoma of the prostate without small cell features Current evidence of metastatic disease documented by either bone lesions on radionuclide bone scan and/or soft tissue lesions on computerized tomography/magnetic resonance imaging (CT/MRI) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy Documented prostate cancer progression per Prostate Cancer Working Group (PCWG3) criteria within 6 months prior to screening Chemotherapy-naïve for metastatic castration-resistant prostate cancer (mCRPC), with 1 to 2 prior second generation hormonal therapies in the recurrent non-metastatic setting and/or metastatic setting, and no more than 1 second generation hormonal therapy in the mCRPC setting. Must have progressed during or after second generation hormonal therapy or have documented intolerance to second generation hormonal therapy Participants must meet one of the following criteria regarding tissue submission: Sufficient tumor samples from a newly obtained (fresh) biopsy (obtained during screening); or archival tumor tissue in the form of formalin-fixed paraffin-embedded (FFPE) block or unstained tumor tissue slides. For participants with bone-only disease or inaccessible soft tissue lesions or if the biopsy procedure would pose an unacceptable clinical risk for the participant, submission of tumor tissue obtained from a fresh biopsy is not required. Men must agree to follow specific methods of contraception, if applicable Exclusion Criteria: Active brain metastases Active, known, or suspected autoimmune disease Condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids or adrenal replacement steroid doses are permitted in the absence of active autoimmune disease Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Prior treatment with docetaxel or other chemotherapy for mCRPC. Prior docetaxel for metastatic castration-sensitive prostate cancer is permitted if at least 12 months have elapsed from last dose of docetaxel Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Nivolumab + docetaxel + prednisone<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558-01;Drug: Prednisone<br>* Specified dose on specified days<br>Drug: Docetaxel<br>* Specified dose on specified days<br>|
| Placebo Comparator: Arm B: Placebo + docetaxel + prednisone<br> | Drug: Prednisone<br>* Specified dose on specified days<br>Drug: Docetaxel<br>* Specified dose on specified days<br>Other: Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic progressive free survival (rPFS) assessed by Blinded Independent Central Review (BICR) per Prostate Cancer Working Group (PCWG3) | Up to 530 rPFS events | From the date of randomization to the first date of documented progression or death due to any cause, whichever occurs first, approximately 31 months | 
| Overall Survival (OS) |  | From the date of randomization to the date of death from any cause, approximately 51 months. For participants who are alive, their survival time will be censored at the last date that they were known to be alive | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per PCWG3 |  | From the date of randomization to the date of objectively documented progression or the date of subsequent systemic cancer therapy, whichever occurs first, approximately 31 months | 
| Time to Response per PCWG3 (TTR-PCWG3) determined by BICR |  | From the date of randomization to the date of the first documented complete response (CR) or partial response (PR), approximately 31 months | 
| Duration of Response (DOR) per PCWG3 determined by BICR |  | From the date of first response (CR/PR) to the date of first documented radiographic progression, or death due to any cause, approximately 31 months | 
| Prostate-specific antigen (PSA) Response Rate (PSA-RR) |  | Approximately 31 months | 
| Time to PSA Progression (TTP-PSA) |  | From date of randomization to the date of PSA progression per PCWG3, approximately 31 months | 
| Incidence of Adverse Events (AEs) |  | Approximately 31 months | 
| Incidence of Serious Adverse Events (SAEs) |  | Approximately 31 months | 
| Incidence of AEs leading to discontinuation |  | Approximately 31 months | 
| Incidence of immune-mediated AEs |  | Approximately 31 months | 
| Incidence of deaths |  | Approximately 31 months | 
| Incidence of laboratory abnormalities: Clinical Chemistry Tests |  | Approximately 31 months | 
| Incidence of laboratory abnormalities: Hematology tests |  | Approximately 31 months | 
| Incidence of laboratory abnormalities: Serology tests |  | Approximately 31 months | 
| Median time to pain progression assessed by Brief Pain Inventory-Short Form (BPI-SF) |  | Approximately 31 months | 
| Incidence of changes from baseline in Physical Exam |  | Approximately 31 months | 
| Incidence of changes from baseline in vital signs: Respiratory rate |  | Approximately 31 months | 
| Incidence of changes from baseline in vital signs: Body temperature |  | Approximately 31 months | 
| Incidence of changes from baseline in vital signs: Blood pressure |  | Approximately 31 months | 
| Incidence of changes from baseline in vital signs: Heart Rate |  | Approximately 31 months | 
| Incidence of changes from baseline electrocardiogram (ECG) |  | Approximately 31 months |