Background: Sorafenib (S), a multi TK-inhibitor in combination with topotecan (T), a topoisomerase inhibitor showed preclinical synergistic effects in ovarian cancer but critical toxicity. To avoid cumulative toxicity effects we selected the 5-day schedule of T and a sequential combination with S. Methods: Eligible pts with PROC (progression ≤ 6 mo after ≥ 4 platinum cycles) and ≤ 3 prior CT lines were randomized 1:1 to topotecan 1,25mg/m², d1-5, q21d with either placebo or sorafenib 2x400 mg/daily, d6-15 for 6 chemotherapy cycles, and maintenance sorafenib 2x400 mg/placebo daily for altogether 1 year. The number of treatment lines was stratified (2nd vs. 3rd/4th line). The primary objective was PFS. Secondary endpoints include OAS, objective response, safety and PRO measured by EORTC-QLQC30, OV28 and FOSI. Results: Overall, 172 pts were eligible for analysis. The median age was 59 (25-79 years) whereas 72 pts were in the second and 100 in the ≥ third line. 54.7% of the patients received 6 cycles chemotherapy. Addition of S to T induced no additional severe toxicity grade 3/4, but more hand-foot-skin reactions (13.3% vs. 0%; p<0.001) and alopecia grade 2 (28.9% vs. 13.5%; p=0.015) without significant clinical sequel. TS improved significantly PFS with 6.7 vs. 4.4 months (HR 0.6, 95%CI of 0.43-0.83, p=0.002) and OAS with 17.1 vs. 10.1 months (HR 0.65, 95%CI of 0.45-0.93, p=0.017). Both effects were robust as well in the 2^nd and ≥3^rd line subcohorts. Changes in PRO from baseline to end of therapy were not significantly different between groups, except of one symptom scale (attitude to disease and treatment with more improvement in TS, p=0.038). Conclusions: This is the first trial in PROC providing statistically significant and clinically meaningful improvement in PFS and OAS under implementation of oral multikinase inhibitor. Clinical trial information: NCT01047891