| General information |
| Database: | DB01085 |
| Objective: | Aurora A kinase (AAK) is a key regulator of mitosis and a target for anticancer drug development. Thisphase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors |
| Authors: | Cervantes A, et al |
| Title: | Phase I pharmacokinetic/pharmacodynamic study of MLN8237, an investigational, oral, selective aurora a kinase inhibitor, in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22753585 |
| Trial Design |
| Clinical Trial Id: | NCT00651664 |
| Agent: | alisertib
|
| Target: | aurora kinase A
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | openlabel, phase I, dose-escalation study |
| Key Patients Feature: | Patients 18 years or older of age with histologically or cytologically confirmed metastatic and/or advanced solid tumors (including lymphomas) for which there was no standard curative or lifeprolonging treatment were eligible for enrollment. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1, radiographically or clinically evaluable disease, and adequate hematologic, renal, and hepatic function |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received MLN8237 once daily or twice daily for 7, 14, or 21 consecutive days, follotheyd by 14 days recovery, in 21, 28, or 35day cycles. |
| Primary End Point: | DLT, MTD, pharmacokinetic parameters, antitumor activity |
| Secondary End Point: | NA |
| Patients Number: | 59 |
| Trial Results |
| DLT_MTD: | Neutropenia and stomatitis were the most common DLTs. The MTD for the 7 and 21day schedules was 50 mg twice daily and 50 mg once daily, respectively. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Stable disease was observed and was durable with repeat treatment cycles, administered over 6 months, in 6 patients |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | without notable cumulative toxicity |
| Conclusions: | The recommendedphase II dose of MLN8237 is 50 mg twice daily on the 7day schedule, which is being evaluated further in a variety of malignancies, including in aphase III trial in peripheral Tcell lymphoma. |