Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
2. Adenocarcinoma of the prostate
3. Participants with non-metastatic castration-resistant prostate cancer (NM-CRPC) or metastatic castration-resistant prostate cancer (mCRPC), who in the opinion of the investigator may benefit from treatment with JNJ-56021927
4. Surgically or medically castrated, with testosterone levels of <50 nanogram per deciliter (ng/dL)
5. If the participant is being treated with a gonadotropin-releasing hormone (GnRHa) (ie, participant who has not undergone bilateral orchiectomy), then this therapy must have been initiated at least 4 weeks prior to the Cycle 1 Day 1 visit and must be continued throughout the study
6. Adequate bone marrow and organ function defined as: Hemoglobin (>=9.0 g/dL, independent of transfusion or growth factor support within the prior 7 days); Absolute neutrophil count (>=1000/mm^3 independent of growth factor support within the prior 7 days); Platelet count (>=75,000/mm^3 independent of transfusion or growth factor support within the prior 7 days); Serum albumin (>=3.0 g/dL); Serum creatinine (<=1.5*upper limit of normal (ULN) or calculated creatinine clearance >=50 mL/min/1.73m^2); Total bilirubin [<1.5*ULN (participants with Gilbert's Syndrome may be enrolled if the total bilirubin is <4 mg/dL with predominance of indirect bilirubin >=80% of total bilirubin]); Aspartate aminotransferase or alanine aminotransferase (<=3.0*ULN); Prothrombin time (PT) or partial thromboplastin time (PTT) or international normalized ratio (INR) (PT <=15 sec or INR <=1.2 PTT <=40 sec).

Exclusion Criteria:

1. Known brain metastases
2. Chemotherapy or immunotherapy for the treatment of prostate cancer within 4 weeks of the Study Day 15 (Cycle 1 Day 1) visit
3. Prior treatment with enzalutamide within 8 weeks before first dose of drug probes
4. Therapies that must be discontinued or substituted prior to study visit Day 1, or must be temporarily interrupted during the course of the study, include the following: a) Medications known to lower the seizure threshold within 4 weeks before Study Day 15 (Cycle 1 Day 1) and b) Medications known to induce or inhibit drug metabolizing enzymes (CYP3A4, CYP2C9, CYP2C19 and CYP2C8) or transporter proteins (P-gp, BRCP, OATP1B1, and OATPB3)
5. Participant has known allergies, hypersensitivity, or intolerance to any of the study drugs/drug probes or excipients
6. History of seizure or any condition that may predispose to seizure within 12 months prior to enrollment (Study Day 1); brain arteriovenous malformation; or intercranial masses such as schwannoma or meningioma that is causing edema or mass effect
7. Participants with poor metabolizer genotype for CYP2C9 (*2, *3), or CYP2C19 (*2, *3, *4, *8)