Apalutamide, Abiraterone Acetate, and Prednisone in Treating Participants With Metastatic Castration Resistant Prostate Cancer

Recruitment & Eligibility

Status: Active, not recruiting

Sex: Male

Target Recruitment: 7

Inclusion Criteria

Inclusion Criteria: - Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features - Presence of metastatic disease that can be biopsied by any methodology applicable - Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration) - Serum testosterone level =< 50 ng/dL at the screening visit - Progressive disease defined as one or more of the following three criteria (NOTE: Patients who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen): - PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 weeks between each determination. The PSA value at the screening visit should be >= 2 ng/mL - Soft tissue disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) - Bone disease progression defined by two or more new lesions on bone scan - Patients previously treated with chemotherapy must have no more than two prior chemotherapy regimens for the treatment of metastatic prostate cancer - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 - Serum albumin >= 3.0 g/dL - Serum potassium >= 3.5 mmol/L - Estimated life expectancy of >= 6 months - Able to swallow the study drug and comply with study requirements - Willing and able to give informed consent - Tumor specimen obtained prior to treatment initiation by interventional radiology guided biopsy will be interrogated per immunohistochemistry (IHC) and features should be as follows for a patient to be eligible - Overexpression of androgen receptor (AR)-C terminal and AR-N terminal and PTEN with lack of ARV7 expression along with and ki67 =<10% - No combined RB loss and p53 mutation and - No expression of neuroendocrine markers CD56 and chromogranin (all markers assessed by standardized IHC protocols) - 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 - The methods must consist of a condom and the use of another barrier method (such as a diaphragm or cervical/vault caps) with a spermicidal agent. Your female partner can choose to use an intrauterine device or system (intrauterine device [IUD] or intrauterine system [IUS]) or use birth control pills, injections, or implants instead of a barrier method Exclusion Criteria: - Known allergy to the study drugs or any of its components - Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated - Known metastases to the brain - Absolute neutrophil count < 1000/uL at the screening visit - Platelet count =< 100,000 x 10^9/uL at the screening visit - Hemoglobin < 9 g/dL at the screening visit at the screening visit - NOTE: patients may not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at the screening visit - Total bilirubin (Tbili) > 1.5 times the upper limit of normal at the screening visit - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal at the screening visit - Creatinine (Cr) > 2 mg/dL at the screening visit - History of another malignancy within the previous 2 years with > 30 % probability of relapse other than curatively treated non-melanomatous skin cancer - Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-alpha reductase inhibitors (finasteride, dutasteride), estrogens, chemotherapy, or biologic therapy within 4 weeks of enrollment (day 1 visit) - Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) of enrollment (day 1 visit) - Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery - Structurally unstable bone lesions suggesting impending fracture - History of seizure or any condition that may increase the patient's seizure risk. Also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 - Clinically significant cardiovascular disease including: - Myocardial infarction within 6 months - Uncontrolled angina within 6 months - Congestive heart failure New York Heart Association (NYHA) class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months results in a left ventricular ejection fraction that is >= 45% - History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes) - Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec - History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place - Hypotension (systolic blood pressure < 86 millimeters of mercury or bradycardia with a heart rate of < 50 beats per minute on any ECG taken at the screening visit - Bradycardia with a heat rate of < 50 beats per minutes in the screening ECG, unless pharmaceutically induced and reversible - Chronically uncontrolled hypertension as indicated by consistently elevated resting blood pressure (systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg) during screening - Have used or plan to use from 30 days prior to enrollment (day 1 visit) through the end of the study the following medications known to lower the seizure threshold: - Aminophylline/theophylline - Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone) - Bupropion - Insulin - Lithium - Pethidine - Phenothiazine antipsychotics (e.g., prochlorperazine [compazine], chlorpromazine, mesoridazine, thioridazine) - Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine) - Prior use of ketoconazloe, enzalutamide, abiraterone or apalutamide or participation in a previous clinical trial of ketoconazloe,enzalutamide, abiraterone or apalu

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events;Composite progression free survival (PFSc);Overall survival (OS);Androgen expression signaling;Survival escape pathway signaling;PSA measurement

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