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

Official title

A Phase 2 Randomized Study of Abiraterone Acetate, Enzalutamide or Apalutamide as First Line Therapy in Veterans With Castrate-sensitive Prostate Cancer

Overview

The investigators have used national VHA data to demonstrate real-world efficacy of abiraterone and enzalutamide in Veterans with mCRPC. In the real-world that is the VHA, the investigators have successfully estimated g values that accurately predict OS and the use of this metric in other settings should now be explored. In the egalitarian system that is the VHA the treatment of prostate cancer is excellent and uniform across the US. The choices made are clearly personalized, given not all men received all therapies and that younger Veterans were treated more aggressively. But with survivals that rival those in registration trials that enroll optimally fit individuals usually not encumbered by the co-morbidities that afflict many Veterans, the outcomes are testimony to the fact that for this common malady of older Veterans with whom VA physicians have broad experience the care administered is unsurpassed. Importantly this care at least as regards Veterans with mCRPC demonstrates that given equal access to health care, all men with prostate cancer fare comparably well. As our sophistication in categorizing cancers molecularly has increased this study will look to better examine any emerging differences across study participants.

Interventions

• Drug Abiraterone acetate
  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
• Drug Apalutamide
  Apalutamide (ERLEADA®), 240 mg (four 60 mg tablets) administered orally once daily + physician's choice GnRH agonist/antagonist \[unless the Veteran has had prior bilateral orchiectomy\].
• Drug Enzalutamide
  Enzalutamide (XTANDI®), 160 mg (four 40 mg capsules) administered orally once daily + physician's choice GnRH agonist/antagonist \[unless the Veteran has had prior bilateral orchiectomy\].

Primary outcome measures

• Tumor growth rate (g) [Time frame: 2 years]
• Testosterone levels [Time frame: 2 years]

Secondary outcome measures (1)

• PSA Response [Time frame: 2 years]

Eligibility criteria

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 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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• VA Greater Los Angeles Healthcare System — Los Angeles
• James A. Haley Veterans Administration Hospital — Tampa
• VA Ann Arbor Healthcare System — Ann Arbor
• VA St. Louis Health Care System — St Louis
• VA New York Harbor Healthcare System — New York
• James J. Peters VA Medical Center — The Bronx
• VA Hudson Valley Health Care System — Wappingers Falls
• W.G. Bill Hefner Medical Center — Salisbury
• … and 4 more centers

Identifiers

NCT: NCT05422911 · 1641701 · 21-35

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗