A Randomized, Double-blind, Placebo Controlled, Multicenter Phase II Study to Assess the Efficacy and Safety of Sorafenib Added to Standard Treatment With Topotecan in Patients With Platinum-resistant Recurrent Ovarian Cancer

Trial ID #	NCT01047891
Phase	II
Drug Class	Angiogenesis Inhibitors: Multi-targeted RTK
Drug Name	Sorafenib
Alternate Drug Names	BAY 43-9006, BAY 43-9006 tosylate salt, BAY 54-9085, Nexavar, SFN
Drugs in Trial	Sorafenib, Topotecan
Eligible Participant	Platinum resistant or refractory ovarian cancer with ≤ 2 prior therapies
Patients Enrolled	185, median 2 prior therapies (1-3); 90% primary Pt-R, 10% primary Pt-Rf
Therapy Setting	Recurrence
Study Design	Double Blind, Randomized
Endpoints	ORR, DoR, PFS, OS, evaluated per RECIST
Efficacy	Sor+Top (n=83) vs Placebo+Top (n=89): ORR: 31 vs 12% (p=0.036) DoR: 21.0 vs 14.0 months (p=0.24) PFS: 6.7 vs 4.4 months, HR: 0.60 (0.43-0.83, p=0.0018) OS: 17.1 vs 10.1 months, HR: 0.65 (0.45-0.93, p=0.017)
Clinically Significant Adverse Events	Sor+Top vs Placebo+Top: Serious AE: overall (59 vs 51%), abdominal pain (10 vs 6%) Grade 3-4 AE: leukopenia (69 vs 53%), neutropenia (55 vs 54%), thrombocytopenia (28 vs 22%), hand-foot skin reaction (13 vs 0%)
Conclusion	Sorafenib given with topotecan (5-day schedule) and continued as maintenance therapy results in a significant improvement in ORR, PFS and OS
Reference	Chekerov R et al. Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol (2018) 19(9):1247-1258 https://pubmed.ncbi.nlm.nih.gov/30100379/