Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors.
Cancer
; 122(16): 2524-33, 2016 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-27192055
ABSTRACT
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/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.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/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.CONCLUSIONS:
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;1222524-33. © 2016 American Cancer Society.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Neoplasms
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Cancer
Year:
2016
Document type:
Article