Background: Docetaxel is the standard first-line chemotherapy for mCRPC. Most patients experience disease response or stabilization on docetaxel, although no treatment is currently used to maintain efficacy when docetaxel is stopped. Tasquinimod is an oral, quinoline-3-carboxamide derivative that binds to S100A9, with immunomodulatory, anti-angiogenic and anti-metastatic activity and a manageable safety profile. Tasquinimod demonstrated significantly improved PFS (7.6 v 3.3 mo) in asymptomatic to mildly symptomatic mCRPC (Pili, R. et al. J Clin Oncol 2011; 29: 4022-8) and is in phase III development. The purpose of this study is to assess whether tasquinimod used as a switch maintenance therapy can postpone cancer progression in patients with mCRPC with response or stabilization on first-line docetaxel therapy. Methods: Design: Phase II, multinational, randomized, double-blind, placebo-controlled proof of concept study. Patients with mCRPC will be randomly assigned (ratio 1:1) to receive tasquinimod or placebo. Randomization will be stratified by presence of visceral metastases and opioid analgesic use for cancer-related pain. Patient population: 140 male patients aged ≥18 years with histologically documented mCRPC and ECOG performance status 0 or 1 will be randomized. Before study entry, patients should have received ≥6 cycles of docetaxel and not experienced cancer progression according to PSA and RECIST criteria. Recruitment is ongoing. Dosage: Patients will receive a starting dose of 0.25 mg/day tasquinimod or placebo, with escalation to 0.5 mg/day and 1 mg/day based on individual safety and tolerability. Primary endpoint: Radiological PFS including skeletal-related events, from randomization to the date of radiological progression or death due to any cause. Secondary endpoints: Overall survival, symptomatic PFS, quality of life, pharmacokinetics, safety, PFS on next-line therapy, time to PSA progression, and changes in biomarkers over time. Clinical trial information: NCT01732549.