The PRESIDE trial: A randomized, double-blind, placebo-controlled phase III efficacy and safety study of continued enzalutamide plus docetaxel after disease progression on enzalutamide alone in patients with metastatic castration-resistant prostate cancer

Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor approved in the US for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) (US PI, 2014) and in the EU for the treatment of asymptomatic/mildly symptomatic men with mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated, or those whose disease has progressed on or after doxetaxel (DTX) therapy (EU SmPC, 2014). The PRESIDE study (NCT02288247 ) will evaluate the efficacy and safety of continued ENZA treatment vs placebo (PBO) when starting docetaxel plus prednisolone (PRED) after disease progression on first-line ENZA in chemotherapy-naïve mCRPC patients. Methods: PRESIDE will consist of an open-label treatment period with ENZA (period 1), followed by a randomized double-blind treatment with continued ENZA or PBO in addition to DTX plus PRED (period 2). Eligibility criteria include confirmed prostate adenocarcinoma, metastatic disease, prostate-specific antigen (PSA) progression on androgen deprivation or surgical castration, Eastern Cooperative Oncology Group performance status 0-1, testosterone ≤50 ng/dL, and minimally symptomatic patients (Brief Pain Inventory Short Form, question 3, < 4 in the absence of opiate analgesia). In period 1, all patients will receive open-label ENZA 160 mg/day until radiographic progression and/or PSA progression with rapid PSA doubling time. In period 2, patients with confirmed disease progression on ENZA alone will be randomized to continue ENZA 160 mg/day or receive PBO. All patients will also receive therapy with DTX 75 mg/m2 every 3 weeks plus PRED 10 mg/day. The primary end point is radiographic progression-free survival. Secondary end points include PSA and pain progression, PSA and radiographic response, opiate use for cancer-related pain, skeletal related events and quality of life. Planned enrolment is 650 patients in 90 sites across Europe for period 1, with ≥137 patients in each randomized arm for period 2. Recruitment commenced in December 2014.