A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy
Condition: Stage III Prostate Adenocarcinoma AJCC v7; Stage III Prostate Cancer AJCC v7; Stage IV Prostate Adenocarcinoma AJCC v7; Stage IV Prostate Cancer AJCC v7
MeSH terms: Prostatic Neoplasms; Adenocarcinoma
Intervention: Abiraterone Acetate; Apalutamide; Degarelix; Indomethacin; Laboratory Biomarker Analysis; Prednisone
Intervention description: Given PO; Given PO; Given SC; Given PO; Correlative study; Given PO
Intervention MeSH terms: Prednisone; Cortisone; Indomethacin; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well apalutamide, abiraterone acetate, prednisone, degarelix,
      and indomethacin work in treating patients with prostate cancer that has spread from where it
      started to nearby tissue or lymph nodes before surgery. Androgen can cause the growth of
      tumor cells. Hormone therapy using apalutamide, abiraterone acetate, prednisone, degarelix,
      and indomethacin may fight prostate cancer by lowering the amount of androgen the body makes
      and/or blocking the use of androgen by the tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide written informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Documented histologically confirmed adenocarcinoma of the prostate

          -  Willing to undergo prostatectomy as primary treatment for localized prostate cancer

          -  High risk prostate cancer (per National Comprehensive Cancer Network [NCCN] criteria):
             Gleason score 8-10 or T3a or PSA > 20 ng/mL or very-high risk prostate cancer (per
             NCCN criteria): T3b-T4

          -  Serum testosterone >= 150 ng/dL

          -  Able to swallow the study drugs whole

          -  Willing to take abiraterone acetate on an empty stomach (no food should be consumed at
             least two hours before and for one hour after dosing)

          -  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

          -  Medications known to lower the seizure threshold (see list under prohibited meds) must
             be discontinued or substituted at least 4 weeks prior to study entry

        Exclusion Criteria:

          -  Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation
             therapy, brachytherapy)

          -  Prior use of apalutamide, abiraterone acetate or degarelix

          -  Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

               -  Hormonal therapy (for example [e.g.] leuprolide, goserelin, triptorelin,
                  degarelix)

               -  Cytochrome P450 (CYP)-17 inhibitors (e.g. ketoconazole)

               -  Antiandrogens (e.g. bicalutamide, nilutamide)

               -  Second generation antiandrogens (e.g. enzalutamide, apalutamide)

               -  Immunotherapy (e.g. sipuleucel-T, ipilimumab)

               -  Chemotherapy (e.g. docetaxel, cabazitaxel)

          -  Evidence of serious and/or unstable pre-existing medical, psychiatric or other
             condition (including laboratory abnormalities) that could interfere with patient
             safety or provision of informed consent to participate in this study

          -  Any psychological, familial, sociological, or geographical condition that could
             potentially interfere with compliance with the study protocol and follow-up schedule

          -  Absolute neutrophil count [ANC] < 1500/mm^3

          -  Platelet count < 100,000/mm^3

          -  Hemoglobin < 9 g/dL

          -  Total bilirubin > 1.5 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 2.5 x ULN; 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

          -  Abnormal kidney function (glomerular filtration rate GFR < 45 mL/min)

          -  Serum albumin < 3 g/dL

          -  Serum potassium < 3.5 mmol/L

          -  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)

          -  Severe or unstable angina, myocardial infarction, symptomatic congestive heart
             failure, arterial or venous thromboembolic events (eg, pulmonary embolism,
             cerebrovascular accident including transient ischemic attacks), or clinically
             significant ventricular arrhythmias within 6 months prior to randomization

          -  History of stroke within the last 5-years

          -  History of gastrointestinal (GI) bleed requiring transfusion

          -  History of peptic ulcer disease requiring treatment within the last 5-years

          -  History of asthma that is nonsteroidal anti-inflammatory drug (NSAID)-induced or with
             asthma that is classified as 'mild-persistent' or worse (based on symptoms occurring
             more than 2 days per week)

          -  Uncontrolled hypertension

          -  Gastrointestinal disorder affecting absorption

          -  Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

          -  Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg
             prednisone/ prednisolone once daily

          -  Any condition that in the opinion of the investigator, would preclude participation in
             this study

          -  Child Pugh class B & C

          -  Pre-existing viral hepatitis