Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).
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TPS5103 Background: Custirsen enhances chemotherapeutic activity via inhibition of clusterin expression. Clusterin is a cytoprotective, antiapoptotic chaperone upregulated by anticancer therapies that confers treatment resistance. In a phase 2 study, mCRPC patients who had progressed within 6 mos of completing first-line docetaxel (DOC)/prednisone (P) and who were retreated with DOC/P and custirsen had a median overall survival of 15.8 mos. Lowering of serum clusterin level during second-line treatment was associated with significantly longer survival. CbzP has recently shown a survival advantage in patients with prostate cancer that has progressed after DOC therapy. The AFFINITY study was designed to evaluate in a larger study whether adding custirsen to CbzP will further improve survival in this patient population. Methods: AFFINITY was initiated in August 2012. Eligible patients in this phase 3, international, multicenter, open-label trial must have received ≥225 mg/m2 of DOC; have progressive disease as defined by RECIST 1.1, bone scan progression, and/or serum prostate-specific antigen level; have metastatic disease of the chest/abdomen/pelvis/bone; have adequate renal and liver function; and have a Karnofsky score ≥70%. Patients may have received up to 1 DOC regimen as well as abiraterone and/or enzalutamide. Approximately 630 patients will receive 21d cycles of Cbz (25 mg/m2IV q21d) + P (10 mg PO/d), either alone or with custirsen 640 mg IV given for 3 loading doses and then weekly until disease progression, unacceptable toxicity, or 10 cycles. The primary efficacy measure is overall survival. The secondary measure is proportion of patients alive without disease progression at Day 140 post-randomization. All efficacy analyses are intent to treat. Adverse events of all patients who receive ≥1 dose of custirsen or Cbz will be included in the safety analysis. This study is sponsored by Teva BPP R&D, Inc., in collaboration with OncoGenex Pharmaceuticals, Inc. Clinical trial information: NCT01578655.
