| General information |
| Database: | DB00582 |
| Objective: | Thisphase 1b study evaluated an entericcoated tablet (ECT) formulation of the investigational Aurora A kinase inhibitor, alisertib (MLN8237). |
| Authors: | Falchook G, et al |
| Title: | Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an entericcoated tablet formulation in nonhematologic malignancies:phase 1 doseescalation study. |
| Journal: | Invest New Drugs. |
| Year: | 2014 |
| PMID: | 24879333 |
| Trial Design |
| Clinical Trial Id: | NCT01045421 |
| 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: | openlabelphase Ib study |
| Key Patients Feature: | Patients with advanced, unresectable, nonhematologic malignancy were eligible for inclusion. Study participants wererequired to be at least 18 years of age and have an EasternCooperative Oncology Group performance status (ECOG PS) of 0 or 1, as well as adequate hematologic, renal, and hepaticfunction, defined as: total bilirubin less than and equal to 1.5 ¡Á upper limit ofnormal (ULN); aspartate aminotransferase (AST) and alanineaminotransferase (ALT) less than and equal to 3 ¡Á ULN (elevations less than and equal to 5 ¡Á ULNpermitted if reasonably ascribed to underlying cancer or livermetastases); creatinine clearance more than and equal to 30 mL/min (CockcroftGault); absolute neutrophil count (ANC) more than and equal to 1, 500/mm3 withoutgrowth factor support; platelet count more than and equal to 75, 000/mm3 withouttransfusion requirement. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received oral alisertib ECT for 7 d BID follotheyd by 14 d treatmentfree (21day cycles; 3 + 3 dose escalation schema). |
| Primary End Point: | safety, pharmacokinetics, and antitumor activity, and a recommended phase 2 dose (RP2D) |
| Secondary End Point: | NA |
| Patients Number: | 24 |
| Trial Results |
| DLT_MTD: | The RP2D was determined as 50 mg BID for 7 d (21day cycles). A cycle 1 doselimiting toxicity of grade 4 febrile neutropenia was observed in 1 of 13 patients at RP2D. |
| Objective Response Rate: | Nine patients achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and 6.93* months; *censored). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common drugrelated adverse event (AE) was neutropenia (50%). At doses more than and equal to 40 mg BID, 7 patients had drugrelated AEs that were serious but largely reversible/manageable by dose reduction and supportive care, including 3 with febrile neutropenia. Pharmacokinetic data were available in 24 patients. |
| Conclusions: | Alisertib ECT was generally well tolerated in adults with advanced, nonhematologic malignancies. The RP2D is 50 mg BID for 7 d and is being evaluated in ongoingphase 2 studies. |