Open‐label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors

BACKGROUND This study was designed to determine the safety, tolerability, and pharmacokinetics (PK) of alisertib (MLN8237) in combination with docetaxel and to identify a recommended dose for the combination. METHODS Adults with metastatic cancer were treated on 21‐day cycles with alisertib (10, 20, 30, or 40 mg) twice daily on days 1 to 7 or days 1 to 5 and with docetaxel (75 or 60 mg/m2) on day 1. The primary objectives were to assess the safety and tolerability of the combination and to determine the recommended phase 2 dose (RP2D) for future studies. Secondary objectives included an efficacy assessment and PK analyses of docetaxel and alisertib. RESULTS Forty‐one patients participated. Eight dose levels were explored with various doses of alisertib and docetaxel. The dose‐limiting toxicities were neutropenic fever, neutropenia without fever, stomatitis, and urinary tract infection. The RP2D of this combination was 20 mg of alisertib twice daily on days 1 to 7 and intravenous docetaxel at 75 mg/m2 on day 1 in 21‐day cycles. Eight of the 28 patients (29%) who were efficacy‐evaluable had objective responses. These included 1 complete response in a patient with bladder cancer, 6 partial responses in patients with castration‐resistant prostate cancer, and 1 partial response in a patient with angiosarcoma. Concomitant administration of alisertib did not produce any clinically meaningful change in docetaxel PK. CONCLUSIONS Alisertib at 20 mg twice daily on days 1 to 7 with intravenous docetaxel at 75 mg/m2 on day 1 in a 21‐day cycle was well tolerated, and the combination demonstrated antitumor activity. Cancer 2016;122:2524–33. © 2016 American Cancer Society. Alisertib is an aurora A kinase inhibitor and may enhance the activity of the taxane docetaxel. The combination of alisertib and taxane is tolerable and shows activity across various cancer types.