This study investigates the pathologic effects of the combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix when given for 12 weeks prior to prostatectomy in men with localized prostate cancer. Enzalutamide, an androgen receptor (AR) antagonist, blocks binding of testosterone to the AR as well as preventing nuclear translocation of the AR and DNA binding. Abiraterone acetate inhibits the CYP17 pathway, which is involved in the formation of androgens. Dutasteride is a 5-alpha-reductase inhibitor which blocks conversion of testosterone to dihydrotestosterone. Degarelix, a gonadotropin-releasing hormone (GnRH) antagonist, binds to GnRH receptors on the pituitary gland thus suppressing testosterone release from the testes. Therefore it is hypothesized that the combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix will result in near-complete AR inhibition and produce favorable pathologic changes after 12 weeks of therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
160mg
1000mg
5mg twice daily (to blunt mineralocorticoid side effects from abiraterone)
0.5mg
240mg SC loading dose on day 1, then three 80mg SC injections every 4 weeks thereafter
Johns Hopkins Hospital
Baltimore, Maryland, United States
Proportion of prostatectomy specimens with a complete response rate
Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy
Time frame: 12 weeks
Proportion of prostatectomy specimens with a negative surgical margin rate
Proportion of prostatectomy specimens with a negative surgical margin rate after 12 weeks of therapy
Time frame: 12 weeks
Proportion of prostatectomy specimens with a near-pathologic complete response
Proportion of prostatectomy specimens with a near-pathologic complete response (\<=5mm of residual tumor) after 12 weeks of therapy
Time frame: 12 weeks
Proportion of prostatectomy specimens with pathologic T3 disease
Proportion of prostatectomy specimens with pathologic T3 disease after 12 weeks of therapy
Time frame: 12 weeks
Change in immunologic parameters (TREC levels and antibody responses)
Change in immunologic parameters (TREC levels and antibody responses) after 12 weeks of enzalutamide, abiraterone acetate, dutasteride and degarelix and an additional month of degarelix monotherapy (16 weeks total).
Time frame: 16 weeks
Proportion of radiographic disappearance of MRI detectable significant prostate nodules
Proportion of radiographic disappearance of MRI detectable significant prostate nodules after 12 weeks of therapy.
Time frame: 12 weeks
Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy
Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy (12 weeks of therapy + 1 year = 64 weeks)
Time frame: 64 weeks
PSA progression free survival
The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued.
Time frame: 2 years after last accrual
Overall survival
The overall survival estimate two years after the last patient has accrued.
Time frame: 2 years after last accrual
Incidence and severity of adverse events
Safety as assessed by the incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute - Common Terminology Criteria for adverse events (CTCAE) version 4.0
Time frame: 16 weeks
Exploratory biomarkers assessment
Exploratory biomarker Assessment. Examples of these may include, but are not limited to: assessment for genomic PTEN loss via fluorescence in situ hybridization (FISH), PTEN immunohistochemistry (IHC), assessment for alteration in MYC/chromosome 8q24 via FISH, RNAseq analysis, serum drug/androgen levels and intraprostatic drug/androgen levels.
Time frame: 16 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.