Disease	Mesothelioma
Stage of Disease/Treatment	Metastatic/advanced
Prior Therapy	1 prior regimen
Type of Study	Phase II, single arm
Primary Endpoint	4‐month disease control rate
Secondary Endpoints	Progression‐free survival, overall survival, overall response rate, safety, correlative endpoint
Additional Details of Endpoints or Study Design
Treatment Plan: We conducted a single‐arm, single‐institution phase II trial of alisertib administered 50 mg twice daily for 7 days every 21 days at the University of Texas MD Anderson Cancer Center. Patient eligibility included unresectable pleural or peritoneal mesothelioma, up to four lines of prior therapy, including at least one prior platinum‐pemetrexed combination therapy, and adequate organ function.
Assessments: Efficacy was assessed by either modified RECIST (mRECIST; preferred) or RECIST criteria (if mRECIST could not be performed) every 6 weeks. Archival or fresh tissue at baseline was collected to assess MYC copy number and evaluate the association between short‐term responses and subgroups defined based on FISH criteria for MYC gene analysis.
Endpoints and Statistical Analysis: The primary endpoint was 4‐month disease control rate and secondary endpoints were survival (progression‐free and overall), overall response rate, duration of response, safety/toxicity, the association between responses and subgroups defined by MYC copy number gain. An interim analysis was planned after 24 evaluable patients were enrolled. Evaluable patients were identified as those who completed at least one cycle (i.e., 50‐mg doses twice daily for days 1–7 of first cycle) of alisertib treatment. The trial was conducted according to the Simon's minimax two‐stage design and the disease control rate at 4 months was estimated accordingly. It was assumed that the new regimen would have a target disease control rate of 50% at 4 months. A disease control rate of 30% or lower would be considered a failure and the new regimen would be rejected under this circumstance. When the probability of accepting a “bad” regimen (i.e., disease control rate ≤ 30%) is 0.05 and the probability of rejecting a “good” regimen (i.e., disease control rate ≥ 50%) is 0.10, Simon's minimax design requires entry of 24 patients in the first stage. If 7 or fewer patients are alive and free of disease progression at 4 months following initiation of treatment, the trial would be stopped and the regimen declared as ineffective. If 8 or more patients were alive and progression free at 4 months, 29 more patients would be entered in the study to reach a total of 53 patients. By the end of the study, the new regimen would be rejected if the disease control rate is less than or equal to 21/53 and would be accepted otherwise.
Investigator's Analysis	Active but results overtaken by other developments