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- Title
Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors.
- Authors
Graff, Julie N.; Higano, Celestia S.; Hahn, Noah M.; Taylor, Matthew H.; Zhang, Bin; Zhou, Xiaofei; Venkatakrishnan, Karthik; Leonard, E. Jane; Sarantopoulos, John
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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/m(2) ) 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.<bold>Results: </bold>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/m(2) 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.<bold>Conclusions: </bold>Alisertib at 20 mg twice daily on days 1 to 7 with intravenous docetaxel at 75 mg/m(2) 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.
- Subjects
CANCER treatment; KINASE inhibitors; DOCETAXEL; NEUTROPENIA; CLINICAL trials
- Publication
Cancer (0008543X), 2016, Vol 122, Issue 16, p2524
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.30073