| General information |
| Database: | DB01086 |
| Objective: | Aurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This singlearmphase II study assessed singleagent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinumrefractory or resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. |
| Authors: | Matulonis UA, et al |
| Title: | Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinumresistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. |
| Journal: | Gynecol Oncol. |
| Year: | 2012 |
| PMID: | 22772063 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | alisertib
|
| Target: | aurora kinase A
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | advanced epithelial ovarian, fallopian tube, or primary peritoneal carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | singlearmphase II study |
| Key Patients Feature: | Adult women with malignant, platinumtreated disease |
| Biomarker: | AAK expression/copy number in archived samples |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received MLN8237 50mg orally twice daily for 7 days plus 14 days' rest (21day cycles) |
| Primary End Point: | combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA125 criteria. |
| Secondary End Point: | response duration, clinical benefit rate, progression free survival (PFS), timetoprogression (TTP), and safety. |
| Patients Number: | 31 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for more than and equal to 3 months in 6 (19%). |
| Median Time to Progression: | 1.9 months |
| Median PFS A vs. C: | 1.9 months |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most common drug related grade more than and equal to 3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia. |
| Conclusions: | These data suggest that MLN8237 has modest singleagent antitumor activity and may produce responses and durable disease control in some patients with platinumresistant ovarian cancer. MLN8237 is currently undergoing evaluation in aphase III trial with paclitaxel in recurrent ovarian cancer. |