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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexMale
• Healthy volunteersNo

You may be able to join if

• 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 2 or less (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 morphologic evidence of small-cell features in either a recently obtained sample or in the archival sample at the time of diagnosis.
• Have previously begun within 120 days of randomization 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).
• Laboratory tests meet minimum safety requirements:
• Hepatic: AST ≤2.5 X institutional ULN, ALT ≤2.5 X institutional ULN, Total bilirubin ≤1.5X upper limit of normal (ULN) [except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10X ULN].
• Renal: Creatinine clearance ≥30 ml/min or serum creatinine ≤1.8 mg/dl
• Hematological: Platelet count ≥100,000/mm^3; Hemoglobin >9 g/dL; ANC >1 X10^9/L
• Serum potassium >3 mEq/L

You cannot join if

• Subjects with any of the following will not be enrolled:
• Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, apalutamide or enzalutamide or darolutamide 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 other than bicalutamide, 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.
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).
• Patients who are receiving any other investigational agents concurrently.
• Clinically significant heart disease as evidenced by New York Heart Association (NYHA) Class III-IV heart disease.
• Child-Pugh Class B and C

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

abiraterone. A steroidal compound with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex; CYP17A1), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels. NCI Drug Dictionary

deuterated enzalutamide. A deuterated form of enzalutamide, an orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Upon administration, deuterated enzalutamide competitively binds to and inhibits the activity of ARs expressed on prostate cancer cells, which impairs nuclear translocation and DNA binding, resulting in apoptosis of prostate cancer cells. This results in a reduction in prostate cancer cell growth. AR overexpression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance. Deuterium incorporation, by replacing the hydrogen atoms of the N-CH3 moiety with deuterium atoms, decreases enzalutamide's metabolism and allows for an increased pharmacokinetic profile, thereby enhancing its anti-tumor efficacy compared to non-deuterated enzalutamide. As the deuterated form can’t cross the blood-brain barrier (BBB), the deuterated form also reduces the unwanted brain-related side effects of enzalutamide and improves its safety profile. NCI Drug Dictionary

apalutamide. A small molecule and androgen receptor (AR) antagonist with potential antineoplastic activity. Apalutamide binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes. This ultimately inhibits the expression of genes that regulate prostate cancer cell proliferation and may lead to an inhibition of cell growth in AR-expressing tumor cells. NCI Drug Dictionary

Treatments listed in the registry

• Abiraterone acetate (Drug): YONSA® (fine particle formulation abiraterone acetate), YONSA® 500 mg (four 125 mg tablets) or 625 mg (five 125 mg tablets) administered orally once daily in combination with methylprednisolone 4 mg administered orally twice daily + physician's choice GnRH agonist/antagonist [unless the Veteran has had prior bilateral orchiectomy]. Note that in the first four months the YONSA® dose should not exceed 500 mg administered orally once daily. ZYTIGA® (abiraterone acetate) or generic ZYTIGA 1000 mg (four 250 mg uncoated tablets or two 500 mg film-coasted tablets) administered orally once daily in combination with prednisone 5 mg administered orally once daily + physician's choice GnRH agonist/antagonist [unless the Veteran has had prior bilateral orchiectomy].
• Apalutamide (Drug): Apalutamide (ERLEADA®), 240 mg (four 60 mg tablets) administered orally once daily + physician's choice GnRH agonist/antagonist [unless the Veteran has had prior bilateral orchiectomy].
• Enzalutamide (Drug): Enzalutamide (XTANDI®), 160 mg (four 40 mg capsules) administered orally once daily + physician's choice GnRH agonist/antagonist [unless the Veteran has had prior bilateral orchiectomy].

Randomized · Parallel · masking: None

Main goals

• Tumor growth rate (g) (2 years)
• Testosterone levels (2 years)

Other goals

• PSA Response

Planned enrollment: 192 (estimated).

• VA Greater Los Angeles Healthcare System, Los Angeles, California
• James A. Haley Veterans Administration Hospital, Tampa, Florida
• VA Ann Arbor Healthcare System, Ann Arbor, Michigan
• VA St. Louis Health Care System, St Louis, Missouri
• VA New York Harbor Healthcare System, New York, New York
• James J. Peters VA Medical Center, The Bronx, New York
• VA Hudson Valley Health Care System, Wappingers Falls, New York
• W.G. Bill Hefner Medical Center, Salisbury, North Carolina
• VA Portland Health Care System, Portland, Oregon
• Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania
• Michael E. DeBakey VA Medical Center, Houston, Texas
• VA Puget Sound Health Care System, Seattle, Washington

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05422911
• NCI Drug Dictionary: C68845
• NCI Drug Dictionary: C71744
• NCI Drug Dictionary: C92574

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jun 14, 2026. Public record; not medical advice.