TY - JOUR VL - 26 JF - Clinical Cancer Research N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. TI - A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer UR - https://doi.org/10.1158/1078-0432.CCR-19-1638 Y1 - 2020/03// ID - discovery10092744 AV - public IS - 5 EP - 1016 SP - 1009 N2 - PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m^{2} s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection. A1 - Oza, AM A1 - Matulonis, UA A1 - Alvarez Secord, A A1 - Nemunaitis, J A1 - Roman, LD A1 - Blagden, SP A1 - Banerjee, S A1 - McGuire, WP A1 - Ghamande, S A1 - Birrer, MJ A1 - Fleming, GF A1 - Markham, MJ A1 - Hirte, HW A1 - Provencher, DM A1 - Basu, B A1 - Kristeleit, R A1 - Armstrong, DK A1 - Schwartz, B A1 - Braly, P A1 - Hall, GD A1 - Nephew, KP A1 - Jueliger, S A1 - Oganesian, A A1 - Naim, S A1 - Hao, Y A1 - Keer, H A1 - Azab, M A1 - Matei, D SN - 1078-0432 ER -