Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Castration Resistant and Neuroendocrine Prostate Cancer

Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. In this single arm, multi-institutional open label phase 2 clinical trial of alisertib, sixty men were treated with alisertib 50mg twice daily for 7 days every 21-days. Eligibility included metastatic prostate cancer and at least one: small cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; elevated serum neuroendocrine markers. The primary endpoint was six-month radiographic progression free survival. Pre-treatment biopsies were evaluated by whole exome and RNA-seq.]]> Patients with metastatic castration resistant prostate cancer and at least one of the following key eligibility criteria were enrolled across nine centers: small cell NEPC morphology, prostate adenocarcinoma with greater than 50% immunohistochemical (IHC) staining for neuroendocrine markers (e.g., chromogranin, synaptophysin), development of liver metastases in the absence of PSA progression defined by Prostate Cancer Working Group 2 criteria, and serum chromogranin A level ≥5X upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥2X ULN. ]]>