Castrate-sensitive, Castrate-sensitive Prostate Cancer, Metastatic Cancer, Neoplasm, Prostate
Conditions
Keywords
YONSA, zytiga, enzalutamide, apalutamide, growth rate, doubling time
Brief summary
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
DRUGAbiraterone 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 (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 \[unless the Veteran has had prior bilateral orchiectomy\].
DRUGApalutamide
Apalutamide (ERLEADA®), 240 mg (four 60 mg tablets) administered orally once daily + physician's choice GnRH agonist/antagonist \[unless the Veteran has had prior bilateral orchiectomy\].
DRUGEnzalutamide
Enzalutamide (XTANDI®), 160 mg (four 40 mg capsules) administered orally once daily + physician's choice GnRH agonist/antagonist \[unless the Veteran has had prior bilateral orchiectomy\].
Sponsors
Sun Pharmaceutical Industries Limited
VA Puget Sound Health Care System
VA Greater Los Angeles Healthcare System
James A. Haley Veterans Administration Hospital
VA New York Harbor Healthcare System
VA Ann Arbor Healthcare System
Corporal Michael J. Crescenz VA Medical Center
W.G. Bill Hefner Medical Center
Portland VA Medical Center
Michael E. DeBakey VA Medical Center
VA St. Louis Health Care System
VA Hudson Valley HealthCare System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The investigators have used clinical trial data and real-world data including national VHA data to successfully demonstrate how even in the real-world, estimated growth rate (g) values accurately predict OS. This study will test the growth rate (g) endpoint prospectively.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor growth rate (g) | 2 years | Tumor growth rate (g) |
| Testosterone levels | 2 years | Testosterone levels to assess testosterone suppression with androgen deprivation therapy (ADT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response | 2 years | PSA response based Prostate Cancer Working Group 2 guidelines. |
Countries
United States
Contacts
CONTACTTito Fojo, MD, PhD
CONTACTAdrienne A Perea, MPH
Outcome results
None listed