Study Comparing Orteronel Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer

• 50% prostate specific antigen (PSA) response at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Pain response at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Radiographic progression-free survival (rPFS) [ Time Frame: Time from patient randomization to radiographic disease progression or death from any cause, whichever occurs first ] [ Designated as safety issue: No ]

• To determine if orteronel plus prednisone improves 50% prostate specific antigen (PSA) response at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To evaluate whether orteronel plus prednisone improves pain response at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• To determine if orteronel plus prednisone improves radiographic progression-free survival (rPFS) [ Time Frame: Time from patient randomization to radiographic disease progression or death from any cause, whichever occurs first ] [ Designated as safety issue: No ]

This is a randomized, double-blind, multicenter, phase 3 study evaluating orteronel plus prednisone compared with placebo plus prednisone in men with metastatic, castration-resistant prostate cancer (mCRPC) that has progressed following Docetaxel-based therapy

• Drug: Orteronel + prednisone
  Orteronel and prednisone will be administered orally twice a day continuously throughout the study until disease progression is documented
  Other Name: TAK-700
• Drug: Placebo + prednisone
  Placebo and prednisone will be administered orally twice a day continuously throughout the study until disease progression is documented

• Experimental: Orteronel + prednisone
  Intervention: Drug: Orteronel + prednisone
• Placebo Comparator: Placebo + prednisone
  Intervention: Drug: Placebo + prednisone

Inclusion Criteria:

Each patient must meet all of the following 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
• Have progressive disease during or following 1 or 2 regimens of cytotoxic chemotherapy, 1 of which must have included docetaxel. Must have received ≥ 360 mg/m2 of docetaxel within a 6-month period. Patients who were clearly intolerant to docetaxel or develop progressive disease before receiving ≥ 360 mg/m2 are also eligible if they have received at least 225 mg/m2 of docetaxel within a 6-month period and meet the other study entry criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Even if surgically sterilized, patients must Practice effective barrier contraception during the entire study treatment period 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
• Life expectancy of 6 months or more
• Patients who have had up to 2 prior chemotherapy treatments are eligible to participate

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue
• Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone
• Any other therapies for prostate cancer, except for GnRH analogue therapy, must be discontinued 2 weeks before the first dose of study drug
• Radioisotope therapy or external beam radiation therapy within 4 weeks of first dose of study drug
• Documented central nervous system metastases
• Treatment with any investigational compound within 30 days prior ro first dose of study drug (Patients who are in long-term follow-up following active treatment in other trials are eligible)
• 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
• Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
• Uncontrolled nausea, vomiting, or diarrhea despite appropriate medical therapy
• Patients whose prostate cancer is confined to just the prostrate bed or immediate adjacent tissue