@article{discovery10092744,
           month = {March},
           pages = {1009--1016},
         journal = {Clinical Cancer Research},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
            year = {2020},
          volume = {26},
          number = {5},
           title = {A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer},
        abstract = {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.},
             url = {https://doi.org/10.1158/1078-0432.CCR-19-1638},
          author = {Oza, AM and Matulonis, UA and Alvarez Secord, A and Nemunaitis, J and Roman, LD and Blagden, SP and Banerjee, S and McGuire, WP and Ghamande, S and Birrer, MJ and Fleming, GF and Markham, MJ and Hirte, HW and Provencher, DM and Basu, B and Kristeleit, R and Armstrong, DK and Schwartz, B and Braly, P and Hall, GD and Nephew, KP and Jueliger, S and Oganesian, A and Naim, S and Hao, Y and Keer, H and Azab, M and Matei, D},
            issn = {1078-0432}
}