Chicago—Based on recent advances in the management of de novo hormone-sensitive prostate cancer with both docetaxel and abiraterone, and on the evidence of significant activity of cabazitaxel in the post-abiraterone castrate-resistant setting, Anthony M. Joshua, MD and colleagues hypothesized that the addition of cabazitaxel to neoadjuvant abiraterone would improve pathological complete response rates by overcoming mechanisms of resistance in localized high-risk prostate cancer.
The researchers designed the trial to determine the relative efficacy of the addition of cabazitaxel to abiraterone in the neoadjuvant treatment of prostate cancer to achieve a complete response. They described the open label, randomized, two-arm multicenter, phase II trial during a poster session at the 2017 ASCO Annual Meeting in a poster titled Abiraterone +/– Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC-RP) Trial.
The trial’s primary end point is pathological complete response rate; secondary end points include surgical outcomes (positive margins, extracapsular extension,aseminal vesicle or nodal involvement), pharmacodynamic markers in residual tumor (apoptosis, androgen receptor expression, localization, and signaling), biomarkers (intra-prostatic androgen levels), and safety.
Study participants will be randomized in a 1:1 ratio to receive either abiraterone 1000 mg/day, prednisone 5 mg twice a day, leuprolide 22.5 mg subcutaneously every 3 months, and cabazitaxel 25 mg/m2 starting at week 2, with 6 mg pegfilgrastim 24 hours following cabazitaxel (Arm A); or abiraterone 1000 mg/day, prednisone 5 mg twice a day, and leuprolide 22.5 mg subcutaneously every 3 months (Arm B).
Assessments will occur biweekly for the first 12 weeks, then monthly until the prostatectomy, scheduled for 24 weeks after start of treatment. Target accrual is 88 participants within 36 months. The study is powered to detect a 15% difference with 85% power, assuming a one-sided type 1 error rate of 20%. A six-patient safety run-in is included.
One site opened in Canada as of January 1, 2017; four additional sites in Canada and one in Australia are pending. To date, four participants are randomized and are undergoing treatment.
Source: Joshua AM, Fleshner NE, Chin J, et al. Abiraterone +/ Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC-RP) Trial. Abstract of a poster presented at the 2017 American Society of Clinical Oncology, June 5, 2017, Chicago, Illinois. The trial is an investigator-initiated trial led by the Princess Margaret Urology Trials Group with funding from Ontario Institute for Cancer Research and in-kind contributions from Janssen and Sanofi. Clinical trial information: NCT02543255