eprintid: 10092744 rev_number: 15 eprint_status: archive userid: 608 dir: disk0/10/09/27/44 datestamp: 2020-03-10 14:45:50 lastmod: 2021-09-25 23:31:38 status_changed: 2020-03-10 14:45:50 type: article metadata_visibility: show creators_name: Oza, AM creators_name: Matulonis, UA creators_name: Alvarez Secord, A creators_name: Nemunaitis, J creators_name: Roman, LD creators_name: Blagden, SP creators_name: Banerjee, S creators_name: McGuire, WP creators_name: Ghamande, S creators_name: Birrer, MJ creators_name: Fleming, GF creators_name: Markham, MJ creators_name: Hirte, HW creators_name: Provencher, DM creators_name: Basu, B creators_name: Kristeleit, R creators_name: Armstrong, DK creators_name: Schwartz, B creators_name: Braly, P creators_name: Hall, GD creators_name: Nephew, KP creators_name: Jueliger, S creators_name: Oganesian, A creators_name: Naim, S creators_name: Hao, Y creators_name: Keer, H creators_name: Azab, M creators_name: Matei, D title: A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D19 divisions: G99 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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. date: 2020-03 date_type: published official_url: https://doi.org/10.1158/1078-0432.CCR-19-1638 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1731661 doi: 10.1158/1078-0432.CCR-19-1638 pii: 1078-0432.CCR-19-1638 lyricists_name: Kristeleit, Rebecca lyricists_id: RSKRI39 actors_name: Kristeleit, Rebecca actors_id: RSKRI39 actors_role: owner full_text_status: public publication: Clinical Cancer Research volume: 26 number: 5 pagerange: 1009-1016 event_location: United States issn: 1078-0432 citation: Oza, AM; Matulonis, UA; Alvarez Secord, A; Nemunaitis, J; Roman, LD; Blagden, SP; Banerjee, S; ... Matei, D; + view all <#> Oza, AM; Matulonis, UA; Alvarez Secord, A; Nemunaitis, J; Roman, LD; Blagden, SP; Banerjee, S; McGuire, WP; Ghamande, S; Birrer, MJ; Fleming, GF; Markham, MJ; Hirte, HW; Provencher, DM; Basu, B; Kristeleit, R; Armstrong, DK; Schwartz, B; Braly, P; Hall, GD; Nephew, KP; Jueliger, S; Oganesian, A; Naim, S; Hao, Y; Keer, H; Azab, M; Matei, D; - view fewer <#> (2020) A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer. Clinical Cancer Research , 26 (5) pp. 1009-1016. 10.1158/1078-0432.CCR-19-1638 <https://doi.org/10.1158/1078-0432.CCR-19-1638>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10092744/1/Guadecitabine%20and%20carboplatin%20in%20ovarian%20cancer.pdf