Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC Trial)

Inclusion criteria

• Willing and able to provide informed consent;
• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with a minimum of 3 cores positive for tumour;
• Tumour biopsy tissue accessible for downstream evaluation;
• Must be candidates for radical prostatectomy and considered surgically resectable by urologic evaluation;
• High Risk D'Amico score defined as either PSA > 20, Gleason score ≥ 8 as determined by the local pathologist; or T2c-3 based on DRE, pathologic review +/- imaging;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
• No evidence of metastatic disease or nodal disease as determined by radionuclide bone scans and computed tomography (CT)/magnetic resonance imaging (MRI); non-pathological lymph nodes must be less than 15 mm in the short (transverse) axis;
• Able to swallow the study drug(s) as prescribed and comply with study requirements;
• Required initial laboratory values:
• Absolute neutrophil count (ANC) ≥ 1500/μL;
• Platelet count ≥ 100,000/μL;
• Hemoglobin ≥ 90 g/L;
• Creatinine ≤ 175 μmol/L;
• Bilirubin ≤ upper limit of institutional normal (ULN);
• AST/ALT ≤ 1.5 × ULN.

Exclusion criteria

• Received an investigational agent within 4 weeks prior to screening;
• Stage T4 prostate cancer by clinical examination or radiologic evaluation;
• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone below the normal range for the institution;
• Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer;
• Receiving concurrent androgens, estrogens, or progestational agents, or received any of these agents within the 6 months prior to randomization;
• History of another malignancy within the previous 5 years other than curatively treated nonmelanomatous skin cancer and non-muscle invasive bladder cancer;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiovascular disease, unstable angina pectoris, cardiac arrhythmia that is symptomatic or requires active therapy; deep venous thrombosis within 3 months prior to randomization;
• Previous use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988);
• Liver injury or disease (e.g., viral hepatitis, liver failure Child-Pugh Class C).