Open-Label, Multicenter, Phase 1 Study of Alisertib (MLN8237), an Aurora A Kinase Inhibitor, With Docetaxel in Patients With Solid Tumors

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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.


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.


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.


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.

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.

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