Clinical trial NCT02543255: Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC Trial)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: High risk
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-09-07
Enrollment: 76
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Pathological complete response
timeFrame: 24 weeks from start of treatment.
Secondary outcomes:
measure: Pre-operative PSA levels
timeFrame: 24 weeks of treatment
measure: Mean nadir PSA levels
timeFrame: 24 weeks of treatment
measure: Percentage of participants achieving a PSA < 0.2 ng/mL
timeFrame: 24 weeks of treatment
measure: Percentage of participants achieving a 50 and 90% decrease in PSA levels
timeFrame: up to 24 weeks of treatment
measure: Rate of positive surgical margins
timeFrame: up to 24 weeks of treatment
measure: Rate of near-complete response (<5 mm tumour)
timeFrame: up to 24 weeks of treatment
measure: Rate of extracapsular extension
timeFrame: up to 24 weeks of treatment
measure: Rate of positive seminal vesicle involvement
timeFrame: up to 24 weeks of treatment
measure: Rate of nodal involvement
timeFrame: up to 24 weeks of treatment
measure: Tumour proliferation (Ki-67 index)
timeFrame: up to 24 weeks of treatment
measure: Androgen receptor expression
timeFrame: up to 24 weeks of treatment
measure: Incidence of adverse events
timeFrame: up to 24 weeks of treatment
measure: Severity of adverse events
timeFrame: Aup to 24 weeks of treatment
measure: Androgen levels (if optional biopsy tissue is available)
timeFrame: up to 24 weeks of treatment
measure: Genomic alterations between pre- and post-treatment tissue
timeFrame: up to 24 weeks of treatment
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: The Prostate Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Neil E Fleshner, MD, MPH, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Anthony Joshua, BSc (Med), MBBS, PhD, FRACP
role: PRINCIPAL_INVESTIGATOR
References: