Randomized Phase 2 Study of MLN8237, an Aurora A Kinase Inhibitor, Plus Weekly Paclitaxel or Weekly Paclitaxel Alone in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, Preceded by a Phase 1 Portion in Patients With Ovarian or Breast Cancer

Trial ID #	NCT01091428
Phase	I/II
Drug Class	Cell Cycle Inhibitors: AURKA/B
Drug Name	Alisertib
Alternate Drug Names	MLN8237
Drugs in Trial	Alisertib, Paclitaxel
Eligible Participant	Recurrent ovarian cancer
Patients Enrolled	142, median 2 prior therapies
Therapy Setting	Recurrence
Study Design	Double Blind, Randomized
Endpoints	ORR, DoR, PFS, evaluated per RECIST
Efficacy	RP2D: Ali 40mg bid (days 1-3, 8-10, 15-17 of every 28 days) + weekly (days 1, 8, 15 of every 28 days) Pac 60mg/m2 (Pac single drug arm: weekly 80mg/m2) Ali+Pac vs Pac: ORR: 48 (7CR, 23PR, n=63) vs 37% (2CR, 18PR, n=54) DoR: 6.0 vs 7.6 months PFS: 7.6 (6.8-8.8, n=73) vs 5.1 months (4.0-7.2, n=69); HR: 0.75 (0.58-0.96, p=0.14)
Clinically Significant Adverse Events	Ali+Pac vs Pac: Serious AE: overall (29 vs 4%) Grade 3/4 AE: overall (86 vs 20%), neutropenia (77 vs 10%), febrile neutropenia (14 vs 0%), stomatitis (25 vs 0%), anemia (14 vs 3%)
Conclusion	Ali+Pac combination shows promising increase in PFS compared to Pac alone, with a manageable safety profile
Reference	Falchook G et al. Alisertib in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer or Recurrent Ovarian Cancer A Randomized Clinical Trial. JAMA Oncol (2019) 5(1):e183773 https://www.ncbi.nlm.nih.gov/pubmed/30347019