Abiraterone, Enzalutamide, or Apalutamide in Castrate-sensitive Prostate Cancer.

This is an interventional treatment trial for Metastatic Cancer Read More

Inclusion Criteria:

• Veterans must meet the following to be eligible to participate:
• Be willing and able to provide written informed consent for the trial.
• Age ≥18 years of age on day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (on a scale from 0 to 5, with higher scores indicating greater disability and a score of 5 indicating death).
• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet-cell features, or small-cell features in either a recently obtained sample or in the archival sample at the time of diagnosis.
• Have been receiving or will receive androgen-deprivation therapy with a gonadotropin releasing hormone agonist or antagonist or have undergone bilateral orchiectomy (i.e., medical, or surgical castration).
• High risk for the development of progression of disease/metastasis, defined as (i) a minimum of three rising PSA values (PSA1 < PSA2 < PSA3) at an interval of at least 1 week apart; (ii) a PSA level of 2 ng per milliliter (2 μg/L) or greater; and (iii) a PSA doubling time of 9 months or less during continuous androgen-deprivation therapy (bilateral orchiectomy or treatment with gonadotropin-releasing hormone analogue agonists or antagonists) as calculated with the use of the method of Pound et al.
• Has not received abiraterone acetate, enzalutamide, or apalutamide at the time of enrollment.
• Have a predicted life expectancy of >12 months.
• For patients receiving bisphosphonates or denosumab, dose must be stable for at least 4 weeks before randomization.
• Able to swallow the study drug and comply with study requirements.

• Laboratory tests meet minimum safety requirements:

  • Hepatic: AST ≤2.5 X institutional ULN, ALT ≤2.5 X institutional ULN
  • Renal: Creatinine clearance ≥30 ml/min or serum creatinine ≤1.8 mg/dl
  • Hematological: Absolute neutrophil count ≥1000/mm3, Platelet count ≥100,000/mm3; Hemoglobin >9 g/dL Note: The presence of metastatic disease as assessed by any modality is not a contraindication for enrollment.

Exclusion Criteria:

Subjects with any of the following will not be enrolled:

• Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, apalutamide or enzalutamide for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo).
• Treatment with hormonal therapy (e.g., androgen receptor inhibitors, estrogens, 5-alpha reductase inhibitors) or biologic therapy for prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist therapy) within 4 weeks of randomization
• Other malignancy except: (a) Subjects who have been successfully treated and are disease free for 3 years; (b) a history of completely resected non-melanoma skin cancer; or (c) successfully treated in situ carcinoma.
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).
• Deep vein thrombosis or pulmonary embolism in the past 3 months that in the opinion of the physician makes the patient medically unstable.
• Patients who are receiving any other investigational agents concurrently.