Prednisone, Abiraterone, Cabazitaxel, and Enzalutamide in Treating Patients with Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Histologically proven adenocarcinoma of the prostate with metastatic disease
• Progressive disease (PSA, radiologic, symptomatic) following androgen deprivation therapy (LHRH agonist/antagonist +/-anti-androgen); PSA progression defined as baseline increase followed by any PSA increase >= 1 week apart
• Most recent PSA >= 2 ng/ml
• Testosterone < 50 ng/dL
• Anti-androgen withdrawal of first generation AR inhibitors (bicalutamide, nilutamide) is required for 6 weeks if previous duration of stability on them was >= 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,500/ul
• Hemoglobin >= 10 g/dL
• Platelet count >= 100,000/uL
• Creatinine clearance >= 45 ml/min by chronic kidney disease epidemiology collaboration (CKD-EPI) formula
• Potassium > 3.5 mmol/L (or within institutional normal range)
• Bilirubin =< upper limit of normal (ULN) (unless documented Gilbert's disease)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x ULN
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 x ULN
• Subject agrees to use a double barrier method of contraception during the course of study therapy and for at least 3 months after completion of therapy. A double barrier method involves the use of a condom in combination one of the following: sponge, diaphragm, cervical ring with spermicidal gel or foam. Subjects who have had a vasectomy >= 6 months prior to trial therapy and those with female sexual partners who are 55 years old and post-menopausal for 2 years or sterile (by tubectomy, hysterectomy, bilateral oophorectomy) need to agree to use at least a condom
• Ability to sign a written informed consent form
• Subject is willing to stop herbal supplements

Exclusion Criteria

• Prior docetaxel for castration-resistant disease (prior docetaxel for castration-sensitive disease is allowed but not required)
• Prior enzalutamide, abiraterone, cabazitaxel
• History of severe hypersensitivity reaction (>= grade 3) to docetaxel
• History of severe hypersensitivity reaction (>= grade 3) to polysorbate 80 containing drugs
• Concomitant vaccination with yellow fever vaccine
• Prior investigational androgen synthesis (e.g. orteronel) or androgen receptor antagonists (e.g. ARN509, VT464 etc)
• Prior hypersensitivity reaction to capsule components of enzalutamide including labrasol, butylated hydroxyanisole and butylated hydroxytoluene
• Other non-chemotherapeutic investigational agents within 14 days (prior chemotherapy needs a >= 4 week washout)
• Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments)
• Prior isotope therapy with Strontium-89, Samarium or radium-223
• Patients with a history of central nervous system metastases (brain, meninges, spinal cord)
• Imminent risk of pathologic fracture or cord compression
• History of seizures, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months, cerebrovascular accident, and brain arteriovenous malformations
• Uncontrolled severe intercurrent illness or medical conditions including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, uncontrolled diabetes mellitus, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction
• Patients with a "currently active" second malignancy other than non-melanoma skin or superficial urothelial cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered without evidence of disease for 3 years