Abiraterone Acetate, Prednisone, and Apalutamide in Treating Patients with Hormone-Naive Metastatic Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• At least 1 of the 2 following high-risk prognostic factors: • Presence of > 3 lesions on bone scan. Since some prostate cancer bone lesions are not visible on bone scan (e.g. lytic lesions), lesions on computed tomography (CT)/positron emission tomography (PET)-CT may be included if unequivocal after consideration by the PI (Paul Corn, M.D.) • Presence of measurable visceral (excluding lymph node disease) metastasis on CT/PET-CT or magnetic resonance imaging (MRI) (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Absolute neutrophil count (ANC) >= 1,500/ml (unless due to clinically suspected bone marrow infiltration by tumor in which case ANC > 500/ml are allowed) (within 14 days of registration)
• Hemoglobin >= 9.0 g/dL (unless due to clinically suspected bone marrow infiltration by tumor in which case > 8 g/dL allowed) (within 14 days of registration)
• Platelet count >= 100,000/uL (unless due to clinically suspected bone marrow infiltration by tumor in which case > 50,000/uL allowed) (within 14 days of registration)
• Serum albumin >= 3.0 g/dL (within 14 days of registration)
• Calculated creatinine clearance (Cockcroft-Gault equation) >= 30 mL/min (within 14 days of registration)
• Serum potassium >= 3.5 mEg/L (within 14 days of registration)
• Serum magnesium >= 1.6 mg/dL (within 14 days of registration)
• Serum bilirubin < 1.5 x institutional upper limit of normal (IULN) (except for patients with known Gilbert’s disease if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible) (within 14 days of registration)
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN) for patients without liver metastases. (For patients with liver metastases AST or ALT < 4 x IULN is allowed and labs will not be considered as treatment-related toxicity requiring resolution since measured at baseline prior to treatment start) (within 14 days of registration)
• Total alkaline phosphatase levels up to 20 x IULN will be permitted if secondary to bone metastases and will not be considered as treatment-related toxicity requiring resolution since measured at baseline prior to treatment start (within 14 days of registration)
• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
• Patients with resected or irradiated brain metastases or those treated with stereotactic radiation therapy are eligible to enroll, provided the treatment is completed 14 days prior to study registration and patients do not require treatment with steroids that exceeds 10 mg of prednisone daily or equivalent
• Able to swallow study drugs whole as a tablet/capsule
• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
• Patients must agree to tissue collection for correlative studies at the specified time points

Exclusion Criteria

• Small cell prostate cancer
• Abiraterone acetate or apalutamide prescribed for metastatic disease. Patients who initially presented with localized prostate cancer may: (a) have received up to 6 months androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists/antagonists and/or abiraterone acetate and/or apalutamide prior to radical prostatectomy OR (b) up to 2 years of ADT and/or abiraterone acetate and/or apalutamide as part of combination treatment with radiation therapy. In both situations (prior to surgery and/or with external beam radiation therapy [XRT]), the ADT must be completed > 8 months from study registration
• Patients who have received radiation or surgery to the primary tumor within 28 days of cycle 1 day 1. The following exceptions are permitted: * Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy for metastatic disease prior to cycle 1 day 1. Anti-androgens (flutamide, bicalutamide or nilutamide) for subjects receiving an LHRH agonist must be discontinued within 2 weeks of cycle 1 day 1, or * Subjects who have received one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease (e.g., impending cord compression or obstructive symptoms) are eligible if recovered by cycle 1 day 1
• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone daily. Use of inhaled, intranasal, intra-articular and topical steroids are acceptable, as is a short course (i.e. =< 1 day) of corticosteroids to prevent a reaction to the intravenous (IV) contrast used for CT scans
• Active infection (requiring oral or IV antibiotics or antiviral therapy) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• A malignancy (other than the one treated in this study) which required radiotherapy or systemic treatment within the past 5 years, or has a >= 30% probability of recurrence within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)
• Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 160 or diastolic pressures above 100 despite anti-hypertensive therapy. Note that this is NOT a criterion related to particular blood pressure (BP) results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes. (For example doctor’s visit related stress i.e. "white coat syndrome")
• Prolonged corrected QT interval by Fridericia's formula (QTcF) interval on pre-entry electrocardiogram (>= 450 msec)
• Known active or symptomatic viral hepatitis or chronic liver disease
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsade de pointes), New York Heart Association class III-IV heart disease or cardiac ejection fraction measurement of < 40% at baseline
• Patients who have had a history of illness which put them at current risk for bowel perforation such as acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis
• Baseline moderate and severe hepatic impairment (Child Pugh class B & C)
• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
• Gastrointestinal disorder affecting absorption
• Untreated symptomatic spinal cord compression
• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events