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

PRIMARY OBJECTIVES:

I. Determine if a baseline molecular-pathologic androgen receptor response (AR-response)
signature predicts efficacy to abiraterone plus apalutamide in patients with hormone-naive
metastatic prostate cancer (HNMPCa).

SECONDARY OBJECTIVES:

I. Evaluate the efficacy of abiraterone acetate plus apalutamide in patients with HNMPCa.

II. Evaluate the safety of abiraterone acetate plus apalutamide in patients with HNMPCa.

III. Explore the relationship between molecular markers and clinical efficacy outcomes.

OUTLINE:

Patient receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and
apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then for up to 6
months.

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate

- At least 2 of the 3 following high-risk prognostic factors:

- Gleason score of >= 8

- Presence of 3 or more lesions on bone scan

- Presence of measurable visceral (excluding lymph node disease) metastasis on
computed tomography (CT) or magnetic resonance imaging (MRI) (Response Evaluation
Criteria in Solid Tumors [RECIST] 1.1)

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Hemoglobin >= 9.0 g/dL independent of transfusion and/or growth factors within 3
months prior to enrollment

- Platelet count >= 100,000/uL independent of transfusion and/or growth factors within 3
months prior to enrollment

- Serum albumin >= 3.0 g/dL

- Medications known to lower the seizure threshold must be discontinued or substituted
at least 4 weeks prior to study entry

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Calculated creatinine clearance (Cockcroft-Gault equation) >= 45 mL/min

- Serum potassium >= 3.5 mEg/L

- Serum magnesium >= 1.6 mg/dL

- 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)

- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN
for patients without liver metastases. (Note: In subjects with Gilbert's syndrome, 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. For patients with liver metastases
AST or ALT < 4 x IULN is allowed)

- 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

- Treatment within 28 days of cycle 1 day 1: Any prior pharmacotherapy, radiation
therapy, or surgery for metastatic prostate cancer. The following exceptions are
permitted:

- Up to 3 months of antiandrogen therapy (ADT) with LHRH agonists or antagonists or
orchiectomy with or without concurrent anti-androgens 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
may have one course of palliative radiation or surgical therapy to treat symptoms
resulting from metastatic disease (e.g., impending cord compression or
obstructive symptoms) if it was administered at least 28 days prior to cycle 1
day 1. All adverse events associated with these procedures must be resolved at
least to grade 1 by cycle 1 day 1, or

- 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 170 or diastolic pressures above 110 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