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

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05422911
• Other study ID #: 1641701
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: June 2022
• Source: James J. Peters Veterans Affairs Medical Center
• Contact: Tito Fojo, MD, PhD
• Phone: 718-584-9000
• Email: antonio.fojo[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, uniform across the US and indifferent to race. 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, African Americans with prostate cancer fared as well if not better than Caucasians and importantly had better outcomes with abiraterone, an observation needing further exploration as these therapies move up front.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm, Prostate
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	James J. Peters VA Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
James J. Peters Veterans Affairs Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA Progression	Primary Objectives; In Veterans with castrate-sensitive prostate cancer demonstrate that administration of YONSA® (abiraterone acetate) first is not inferior to the administration of physician's choice enzalutamide or apalutamide first with efficacy measured by the rate (g) of tumor growth based on PSA measurement.; In Veterans with castrate-sensitive prostate cancer demonstrate that the efficacy of abiraterone acetate is superior in African American compared to Caucasian Veterans with efficacy measured by the rate (g) of tumor growth based on PSA determination.	2 years
Secondary	PSA Response	PSA response based Prostate Cancer Working Group 2 guidelines.	2 years