Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer.

Summary

Multicenter Phase II study on Decitabine-Carboplatin combination in platinum resistant ovarian cancer patients. Patients will receive study treatment until disease progression is documented, extraordinary medical circumstances occur, intolerable toxicities occur, or the patient withdraws consent.

Timeline

Start

2018-07-30

Primary completion

2021-12

Completion

2021-12

Publications

• Background Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davis J, Giles F, Saba HI, Issa JP. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007 Jan 1;109(1):52-7. doi: 10.1182/blood-2006-05-021162. Epub 2006 Aug 1.
• Background Matei DE, Nephew KP. Epigenetic therapies for chemoresensitization of epithelial ovarian cancer. Gynecol Oncol. 2010 Feb;116(2):195-201. doi: 10.1016/j.ygyno.2009.09.043. Epub 2009 Oct 24.
• Results Bukowski RM, Ozols RF, Markman M. The management of recurrent ovarian cancer. Semin Oncol. 2007 Apr;34(2 Suppl 2):S1-15. doi: 10.1053/j.seminoncol.2007.03.012. No abstract available.
• Results Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011 Sep 23;11(10):719-25. doi: 10.1038/nrc3144.
• Results Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol. 2005 Jan;205(2):275-92. doi: 10.1002/path.1706.
• Results Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010 Jan;31(1):27-36. doi: 10.1093/carcin/bgp220. Epub 2009 Sep 13.
• Results Das PM, Singal R. DNA methylation and cancer. J Clin Oncol. 2004 Nov 15;22(22):4632-42. doi: 10.1200/JCO.2004.07.151.
• Results Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009 Dec;1(2):239-59. doi: 10.2217/epi.09.33.
• Results Taby R, Issa JP. Cancer epigenetics. CA Cancer J Clin. 2010 Nov-Dec;60(6):376-92. doi: 10.3322/caac.20085. Epub 2010 Oct 19.
• Results Peedicayil J. The role of DNA methylation in the pathogenesis and treatment of cancer. Curr Clin Pharmacol. 2012 Nov;7(4):333-40. doi: 10.2174/157488412803305858.
• Results Sang M, Wu X, Fan X, Sang M, Zhou X, Zhou N. Multiple MAGE-A genes as surveillance marker for the detection of circulating tumor cells in patients with ovarian cancer. Biomarkers. 2014 Feb;19(1):34-42. doi: 10.3109/1354750X.2013.865275. Epub 2013 Dec 10.
• Results Gurion R, Vidal L, Gafter-Gvili A, Belnik Y, Yeshurun M, Raanani P, Shpilberg O. 5-azacitidine prolongs overall survival in patients with myelodysplastic syndrome--a systematic review and meta-analysis. Haematologica. 2010 Feb;95(2):303-10. doi: 10.3324/haematol.2009.010611. Epub 2009 Sep 22.
• Results Balch C, Huang TH, Brown R, Nephew KP. The epigenetics of ovarian cancer drug resistance and resensitization. Am J Obstet Gynecol. 2004 Nov;191(5):1552-72. doi: 10.1016/j.ajog.2004.05.025.
• Results Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol. 2010 Oct;28(10):1069-78. doi: 10.1038/nbt.1678.
• Results Blum W, Klisovic RB, Hackanson B, Liu Z, Liu S, Devine H, Vukosavljevic T, Huynh L, Lozanski G, Kefauver C, Plass C, Devine SM, Heerema NA, Murgo A, Chan KK, Grever MR, Byrd JC, Marcucci G. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol. 2007 Sep 1;25(25):3884-91. doi: 10.1200/JCO.2006.09.4169. Epub 2007 Aug 6.
• Results Wang LX, Mei ZY, Zhou JH, Yao YS, Li YH, Xu YH, Li JX, Gao XN, Zhou MH, Jiang MM, Gao L, Ding Y, Lu XC, Shi JL, Luo XF, Wang J, Wang LL, Qu C, Bai XF, Yu L. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses. PLoS One. 2013 May 9;8(5):e62924. doi: 10.1371/journal.pone.0062924. Print 2013.
• Results Wijermans P, Lubbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A. Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol. 2000 Mar;18(5):956-62. doi: 10.1200/JCO.2000.18.5.956.
• Results Plumb JA, Strathdee G, Sludden J, Kaye SB, Brown R. Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res. 2000 Nov 1;60(21):6039-44.
• Results Watts GS, Futscher BW, Holtan N, Degeest K, Domann FE, Rose SL. DNA methylation changes in ovarian cancer are cumulative with disease progression and identify tumor stage. BMC Med Genomics. 2008 Sep 30;1:47. doi: 10.1186/1755-8794-1-47.
• Results Barton CA, Hacker NF, Clark SJ, O'Brien PM. DNA methylation changes in ovarian cancer: implications for early diagnosis, prognosis and treatment. Gynecol Oncol. 2008 Apr;109(1):129-39. doi: 10.1016/j.ygyno.2007.12.017. Epub 2008 Jan 29.
• Results Ibanez de Caceres I, Battagli C, Esteller M, Herman JG, Dulaimi E, Edelson MI, Bergman C, Ehya H, Eisenberg BL, Cairns P. Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Cancer Res. 2004 Sep 15;64(18):6476-81. doi: 10.1158/0008-5472.CAN-04-1529.
• Results Li Y, Hu W, Shen DY, Kavanagh JJ, Fu S. Azacitidine enhances sensitivity of platinum-resistant ovarian cancer cells to carboplatin through induction of apoptosis. Am J Obstet Gynecol. 2009 Feb;200(2):177.e1-9. doi: 10.1016/j.ajog.2008.08.030. Epub 2008 Dec 25.
• Results Frost P, Abbruzzese JL, Hunt B, Lee D, Ellis M. Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells. Cancer Res. 1990 Aug 1;50(15):4572-7.
• Results Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007 Feb 23;128(4):683-92. doi: 10.1016/j.cell.2007.01.029.
• Results Stewart DJ. Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 2007 Jul;63(1):12-31. doi: 10.1016/j.critrevonc.2007.02.001. Epub 2007 Mar 1.
• Results Gomyo Y, Sasaki J, Branch C, Roth JA, Mukhopadhyay T. 5-aza-2'-deoxycytidine upregulates caspase-9 expression cooperating with p53-induced apoptosis in human lung cancer cells. Oncogene. 2004 Sep 2;23(40):6779-87. doi: 10.1038/sj.onc.1207381.
• Results Schwartsmann G, Schunemann H, Gorini CN, Filho AF, Garbino C, Sabini G, Muse I, DiLeone L, Mans DR. A phase I trial of cisplatin plus decitabine, a new DNA-hypomethylating agent, in patients with advanced solid tumors and a follow-up early phase II evaluation in patients with inoperable non-small cell lung cancer. Invest New Drugs. 2000 Feb;18(1):83-91. doi: 10.1023/a:1006388031954.
• Results Pohlmann P, DiLeone LP, Cancella AI, Caldas AP, Dal Lago L, Campos O Jr, Monego E, Rivoire W, Schwartsmann G. Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix. Am J Clin Oncol. 2002 Oct;25(5):496-501. doi: 10.1097/00000421-200210000-00015.
• Results Appleton K, Mackay HJ, Judson I, Plumb JA, McCormick C, Strathdee G, Lee C, Barrett S, Reade S, Jadayel D, Tang A, Bellenger K, Mackay L, Setanoians A, Schatzlein A, Twelves C, Kaye SB, Brown R. Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J Clin Oncol. 2007 Oct 10;25(29):4603-9. doi: 10.1200/JCO.2007.10.8688.
• Results Fang F, Balch C, Schilder J, Breen T, Zhang S, Shen C, Li L, Kulesavage C, Snyder AJ, Nephew KP, Matei DE. A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer. Cancer. 2010 Sep 1;116(17):4043-53. doi: 10.1002/cncr.25204.
• Results Glasspool RM, Brown R, Gore ME, Rustin GJ, McNeish IA, Wilson RH, Pledge S, Paul J, Mackean M, Hall GD, Gabra H, Halford SE, Walker J, Appleton K, Ullah R, Kaye S; Scottish Gynaecological Trials Group. A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer. Br J Cancer. 2014 Apr 15;110(8):1923-9. doi: 10.1038/bjc.2014.116. Epub 2014 Mar 18.
• Results Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
• Results Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO 11 investigators. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. doi: 10.1016/S1470-2045(15)70115-4. Epub 2015 Apr 14.

Drugs

Indications

No indication recorded.