Prostate Cancer
Conditions
Keywords
High risk
Brief summary
This study evaluates the use of chemotherapy with cabazitaxel in addition to abiraterone acetate, prednisone, and leuprolide in neoadjuvant setting prior to radical prostatectomy in patients with high-risk prostate carcinoma. Half of the participants will receive treatment with abiraterone acetate, prednisone, leuprolide, and cabazitaxel, while the other half will receive only abiraterone acetate, prednisone, and leuprolide.
Interventions
Abiraterone acetate will be administered orally as a tablet at 1000 mg/day with prednisone (5 mg oral tablet, twice daily) for 24 weeks.
DRUGLeuprolide
Leuprolide will be administered by subcutaneous injection at 22.5 mg dose every 12 weeks for 24 weeks.
DRUGCabazitaxel with peg-filgrastim
Cabazitaxel will be administered in 6 cycles, with 20 mg/m2 per cycle and 3 weeks between cycles.
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response | 24 weeks from start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants achieving a PSA < 0.2 ng/mL | 24 weeks of treatment | The percentage of participants achieving a PSA \< 0.2 ng/mL following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Pre-operative PSA levels | 24 weeks of treatment | The effect of neoadjuvant leuprolide, and abiraterone acetate and prednisone with and without cabazitaxel on pre-operative PSA will be evaluated. |
| Mean nadir PSA levels | 24 weeks of treatment | The effect of neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel on mean nadir PSA levels will be evaluated. |
| Rate of positive surgical margins | up to 24 weeks of treatment | The rate of positive surgical margins following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Rate of near-complete response (<5 mm tumour) | up to 24 weeks of treatment | The rate of near-complete response (\<5 mm tumour) following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Rate of extracapsular extension | up to 24 weeks of treatment | The rate of extracapsular extension following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Rate of positive seminal vesicle involvement | up to 24 weeks of treatment | The rate of positive seminal vesicle involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Percentage of participants achieving a 50 and 90% decrease in PSA levels | up to 24 weeks of treatment | The percentage of participants achieving a 50 and 90% decrease in PSA levels following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Tumour proliferation (Ki-67 index) | up to 24 weeks of treatment | Tumour proliferation, indexed using Ki-67 immunohistochemistry, following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
| Androgen receptor expression | up to 24 weeks of treatment | Androgen receptor expression will be evaluated using immunohistochemistry following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel. |
| Incidence of adverse events | up to 24 weeks of treatment | Incidence of adverse events will be evaluated for the duration of the study. |
| Severity of adverse events | Aup to 24 weeks of treatment | Severity of adverse events will be evaluated for the duration of the study. |
| Androgen levels (if optional biopsy tissue is available) | up to 24 weeks of treatment | If the participants agrees to optional pre-treatment biopsy, androgen levels will be compared between the pre-treatment tissue samples and prostatectomy tissue. |
| Genomic alterations between pre- and post-treatment tissue | up to 24 weeks of treatment | If the participants agrees to optional pre-treatment biopsy, genomic alterations between the pre-treatment tissue samples and prostatectomy tissue will be evaluated. |
| Rate of nodal involvement | up to 24 weeks of treatment | The rate of nodal involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. |
Countries
Canada
Outcome results
None listed