| General information |
| Database: | DB00581 |
| Objective: | Alisertib is an investigational, oral, selective inhibitor of aurora kinase A. They aimed to investigate the safety and activity of singleagent alisertib in patients with predefined types of advanced solid tumours. |
| Authors: | Melichar B, et al |
| Title: | Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, smallcell lung cancer, non small cell lung cancer, head and neck squamouscell carcinoma, and gastrooesophageal adenocarcinoma: a fivearmphase 2 study. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25728526 |
| 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: | a fivearmphase II study( openlabel, multicentre, phase I/II study |
| Key Patients Feature: | They judged patients eligible for thestudy if were aged 18 years or older and had one offive predefined types of advanced, unresectable, relapsedsolid tumour: breast cancer; smallcell lung cancer; non small cell lung cancer; head and neck squamouscellcarcinoma; and gastrooesophageal adenocarcinoma.To refl ect the heterogeneity of the population, they pros pectively included patients of diff erent subtypes within eachtumour cohort. In the breast cancer cohort, they onlyenrolled women and included hormone receptorpositive(oestrogen, pro ges terone, or both), human epidermal growth factor receptor 2positive (irrespec tive of hormone receptor status), and triplenegativetumour types. For patients with smallcell lung cancer, they included tumours that were either refractory orchemotherapyresistant (defined as no response to orrelapse within 90 days of completion of firstlinechemotherapy) or chemotherapysensitive (defined asrelapse more than 90 days after completion of firstlinechemotherapy). they included patients with both nonsquamous and squamous types of non small cell lungcancer. The cohort with head and neck squamouscellcarcinoma included some patients with diseaseoriginating in the tonsillar or base of tongue area, witharchival tumour specimens available for analysis ofhuman papillomavirus (HPV) subtypes 16 and 18. Finally, for gastrooesophageal adenocarcinoma, they includedpatients with adenocarcinoma of the oesophagus, gastrooesophageal junction, or stomach. they requiredpartici pants to have measurable disease, according toResponse Evaluation Criteria in Solid Tumors (RECIST)version 1.1, 16 an Eastern Cooperative Oncology Groupperformance status of 0 or 1, and adequate haematological, renal, and hepatic function |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Alisertib was administered orally in 21day cycles at the recommendedphase 2 dose of 50 mg twice daily for 7 days follotheyd by a break of 14 days. |
| Primary End Point: | the proportion of patients with an objective response |
| Secondary End Point: | NA |
| Patients Number: | 249 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | an objective response was noted in nine (18%, 95% CI 932) of 49 women with breast cancer, ten (21%, 1035) of 48 participants with smallcell lung cancer, one (4%, 022) of 23 patients with non small cell lung cancer, four (9%, 221) of 45 people with head and neck squamouscell carcinoma, and four (9%, 220) of 47 individuals with gastrooesophageal adenocarcinoma; all were partial responses. |
| Disease Control Rate: | NA |
| Median Time to Progression: | Median time to progression was 5.4 months (95% CI 2.6-7.9) in breast cancer cohort. 2.6 months (95% CI 1.4-3.8) in lung cancer cohort. In the non small cell lung cancer, head and neck squamouscell carcinoma, and gastrooesophageal adenocarcinoma cohorts, median time to progression was 3.0 months (95% CI 2.4-4.7), 2.7 months (1.4-3.2), and 1.5 months (1.3-2.8), respectively. |
| Median PFS A vs. C: | median progression free survival was 5.4 months (95% CI 2.6-7.9) in breast cancer cohort. 2.1 months (95% CI 1.4-3.4) in lung cancer cohort. In the non small cell lung cancer, head and neck squamouscell carcinoma, and gastrooesophageal adenocarcinoma cohorts, median progression free survival was 3.1 months (95% CI 2.4-4.4), 2.7 months (95% CI 1.4-3.9), and 1.5 months (1.3-2.8), respec tively |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent drugrelated grade 3-4 adverse events included neutropenia (n=107 [43%]), leukopenia (53 [21%]), and anaemia (26 [10%]). Serious drugrelated adverse events were reported in 108 (43%) patients. |
| Conclusions: | These data support further clinical assessment of alisertib in patients with solid tumours, particularly those with breast cancer and smallcell lung cancer. |