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

Study Overview
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Brief Summary
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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.

Official Title
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Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC-RP Trial): A Randomized, Open-label, Multi-centre Phase-2 Study Evaluating the Pathological Complete Response (pCR) Rate Following Neoadjuvant Therapy in Participants With High-risk Prostate Carcinoma for Whom Radical Prostatectomy is Indicated

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone acetate with prednisone
* Drug: Leuprolide
* Drug: Cabazitaxel with peg-filgrastim


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone acetate + prednisone + leuprolide + cabazitaxel<br>Participants randomized to this arm will receive abiraterone acetate (1000 mg/day), prednisone (5 mg twice daily), leuprolide (22.5 mg every 3 months), and cabazitaxel (20 mg/m2, with 6 mg pegfilgrastim administered 24 h following cabazitaxel) prior to radical prostatectomy. | Drug: Abiraterone acetate with prednisone<br>* Abiraterone acetate will be administered orally as a tablet at 1000 mg/day with prednisone (5 mg oral tablet, twice daily) for 24 weeks.<br>Drug: Leuprolide<br>* Leuprolide will be administered by subcutaneous injection at 22.5 mg dose every 12 weeks for 24 weeks.<br>Drug: Cabazitaxel with peg-filgrastim<br>* Cabazitaxel will be administered in 6 cycles, with 20 mg/m2 per cycle and 3 weeks between cycles.<br>|
| Active Comparator: Abiraterone acetate + prednisone + leuprolide<br>Participants randomized to this arm will receive abiraterone acetate (1000 mg/day) , prednisone (5 mg twice daily), and leuprolide (22.5 mg every 3 months) prior to radical prostatectomy. | Drug: Abiraterone acetate with prednisone<br>* Abiraterone acetate will be administered orally as a tablet at 1000 mg/day with prednisone (5 mg oral tablet, twice daily) for 24 weeks.<br>Drug: Leuprolide<br>* Leuprolide will be administered by subcutaneous injection at 22.5 mg dose every 12 weeks for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response |  | 24 weeks from start of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-operative PSA levels | The effect of neoadjuvant leuprolide, and abiraterone acetate and prednisone with and without cabazitaxel on pre-operative PSA will be evaluated. | 24 weeks of treatment | 
| Mean nadir PSA levels | The effect of neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel on mean nadir PSA levels will be evaluated. | 24 weeks of treatment | 
| Percentage of participants achieving a PSA < 0.2 ng/mL | 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. | 24 weeks of treatment | 
| Percentage of participants achieving a 50 and 90% decrease in PSA levels | 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. | up to 24 weeks of treatment | 
| Rate of positive surgical margins | The rate of positive surgical margins following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. | up to 24 weeks of treatment | 
| Rate of near-complete response (<5 mm tumour) | 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. | up to 24 weeks of treatment | 
| Rate of extracapsular extension | The rate of extracapsular extension following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. | up to 24 weeks of treatment | 
| Rate of positive seminal vesicle involvement | The rate of positive seminal vesicle involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. | up to 24 weeks of treatment | 
| Rate of nodal involvement | The rate of nodal involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. | up to 24 weeks of treatment | 
| Tumour proliferation (Ki-67 index) | Tumour proliferation, indexed using Ki-67 immunohistochemistry, following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated. | up to 24 weeks of treatment | 
| Androgen receptor expression | Androgen receptor expression will be evaluated using immunohistochemistry following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel. | up to 24 weeks of treatment | 
| Incidence of adverse events | Incidence of adverse events will be evaluated for the duration of the study. | up to 24 weeks of treatment | 
| Severity of adverse events | Severity of adverse events will be evaluated for the duration of the study. | Aup to 24 weeks of treatment | 
| Androgen levels (if optional biopsy tissue is available) | If the participants agrees to optional pre-treatment biopsy, androgen levels will be compared between the pre-treatment tissue samples and prostatectomy tissue. | up to 24 weeks of treatment | 
| Genomic alterations between pre- and post-treatment tissue | If the participants agrees to optional pre-treatment biopsy, genomic alterations between the pre-treatment tissue samples and prostatectomy tissue will be evaluated. | up to 24 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High risk