None listed
Conditions
Interventions
Group 1 Type of group
Orteronel will be administered at a dose of 400 mg twice daily, orally, in all treatment cycles of the study. The study drug should be taken twice a day at the same time each day, approximately 12 hours apart, and may be taken with or without food.
Group name:Group 2 Type of group
Placebo will be administered orally twice a day continuously throughout the study. Additionally, all patients will receive concomitant gonadotropin-releasing hormone (GnRH) analogue therapy unless they have previously undergone orchiectomy and a testosterone concentration of
Sponsors
Millennium Pharmaceuticals, Inc.,
Eligibility
Sex/Gender
Male
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Voluntary written consent • Male patients 18 years or older • Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma • Radiograph-documented metastatic disease • Progressive disease • Prior surgical castration or concurrent use of an agent for medical castration • Either absence of pain or pain not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to study entry • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 • Even if surgically sterilized, patients must practice effective barrier contraception during the entire study treatment and for 4 months after the last dose of study drug, OR abstain from heterosexual intercourse • Meet screening laboratory values as specified in protocol • Stable medical condition
Exclusion criteria
Exclusion criteria: • Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue • Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone • Received antiandrogen therapy within 6 weeks for bicalutamide and 4 weeks for all others prior to first dose of study drug • Continuous daily use of oral prednisone or oral dexamethasone for more than 14 days within 3 months prior to study • Received prior chemotherapy for prostate cancer with exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening • Exposure to radioisotope therapy within 4 weeks of receiving first dose of study drug; exposure to external beam radiation within 2 weeks of start of screening until receiving the first dose of study drug • Documented central nervous system metastases • Treatment with any investigational compound within 30 days prior to first dose of study drug • Current spinal cord compression, bilateral hydronephrosis or current bladder neck outlet obstruction • Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected • Uncontrolled cardiovascular condition as specified in study protocol • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C • Unwilling or unable to comply with protocol • Uncontrolled nausea, vomiting or diarrhea • Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:rPFS was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by independent central radiology review or death due to any cause, whichever occurred first. Radiographic disease progression was evaluated by computerized tomography (CT) scan or magnetic resonance imaging (MRI) and radionuclide bone scans at regularly scheduled visits. Radiographic disease progression in bone required a confirmatory scan. Radiographic disease progression in soft tissue did not require a confirmatory scan for purposes of analysis. Radiographic disease progression was evaluated by independent central radiology review using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for soft tissue disease and Prostate Cancer Working Group (PCWG2) guidelines for bone disease. Participants who did not reach the endpoint were censored at their last assessment. Measure:Radiographic Progression-free Survival (rPFS) Timepoints:Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years) ; Outcome name:Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier. Measure:Overall Survival Timepoints:Baseline until death (up to 4.7 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The PSA50 is defined as a decline of at least 50 percent (%) from baseline. Measure:Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12 Timepoints:Week 12 ; Outcome name:A favorable CTC count was defined as less than =) 5 counts/7.5 mL in whole blood. Measure:Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12 Timepoints:Week 12 ; Outcome name:Time to pain progression was defined as the time from participant randomization to the first assessment date of pain progression. Pain progression was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: The brief pain inventory-short form (BPI-SF) worst pain score was >=4 with a >=2 point increase over baseline in BPI-SF worst pain score with stable or increased analgesic use; The BPI-SF worst pain score was >=4 but not less than baseline with new or increased (relative to baseline) Step II or Step III analgesic use; The BPI-SF worst pain score was =) Grade 3 Timepoints:Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58) ; Outcome name:ECOG assessed participants performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50 percent of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50 percent of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Worst change was defined as the worst overall change that occurred in ECOG status at any measured time point during the treatment period. Measure:Number of Participants With Worst | — |
Countries
Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungaria, Ireland, Israel, Italy, Japan, Latovia, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kindgdom, United States
Contacts
Public ContactLuis Miguel Melendez
PPD Peru S.A.C.
Outcome results
None listed