Evaluation of TRANSKRIP ® Plus Chemotherapy in Recurrent-Persistent Cervical Cancer

Summary

The purpose of this study is to determine the efficacy and safety the combination of TRANSKRIP ® vs placebo plus Carboplatin/Paclitaxel as first line treatment in patients with recurrent-persistent cervical cancer.

Timeline

Start

2015-01-01

Primary completion

2018-07

Completion

2018-08

Publications

• Background Bruner DW, Wasserman T. The impact on quality of life by radiation late effects. Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1353-5. doi: 10.1016/0360-3016(95)00042-W.
• Background Aaronson SA. Growth factors and cancer. Science. 1991 Nov 22;254(5035):1146-53. doi: 10.1126/science.1659742.
• Background Almonte M, Albero G, Molano M, Carcamo C, Garcia PJ, Perez G. Risk factors for human papillomavirus exposure and co-factors for cervical cancer in Latin America and the Caribbean. Vaccine. 2008 Aug 19;26 Suppl 11:L16-36. doi: 10.1016/j.vaccine.2008.06.008.
• Background Arbyn M, Castellsague X, de Sanjose S, Bruni L, Saraiya M, Bray F, Ferlay J. Worldwide burden of cervical cancer in 2008. Ann Oncol. 2011 Dec;22(12):2675-2686. doi: 10.1093/annonc/mdr015. Epub 2011 Apr 6.
• Background Arce C, Perez-Plasencia C, Gonzalez-Fierro A, de la Cruz-Hernandez E, Revilla-Vazquez A, Chavez-Blanco A, Trejo-Becerril C, Perez-Cardenas E, Taja-Chayeb L, Bargallo E, Villarreal P, Ramirez T, Vela T, Candelaria M, Camargo MF, Robles E, Duenas-Gonzalez A. A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One. 2006 Dec 20;1(1):e98. doi: 10.1371/journal.pone.0000098.
• Background Biancotto C, Frige G, Minucci S. Histone modification therapy of cancer. Adv Genet. 2010;70:341-86. doi: 10.1016/B978-0-12-380866-0.60013-7.
• Background Candelaria M, Cetina L, Perez-Cardenas E, de la Cruz-Hernandez E, Gonzalez-Fierro A, Trejo-Becerril C, Taja-Chayeb L, Chanona J, Arias D, Duenas-Gonzalez A. Epigenetic therapy and cisplatin chemoradiation in FIGO stage IIIB cervical cancer. Eur J Gynaecol Oncol. 2010;31(4):386-91.
• Background Candelaria M, Gallardo-Rincon D, Arce C, Cetina L, Aguilar-Ponce JL, Arrieta O, Gonzalez-Fierro A, Chavez-Blanco A, de la Cruz-Hernandez E, Camargo MF, Trejo-Becerril C, Perez-Cardenas E, Perez-Plasencia C, Taja-Chayeb L, Wegman-Ostrosky T, Revilla-Vazquez A, Duenas-Gonzalez A. A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann Oncol. 2007 Sep;18(9):1529-38. doi: 10.1093/annonc/mdm204.
• Background Candelaria M, Herrera A, Labardini J, Gonzalez-Fierro A, Trejo-Becerril C, Taja-Chayeb L, Perez-Cardenas E, de la Cruz-Hernandez E, Arias-Bofill D, Vidal S, Cervera E, Duenas-Gonzalez A. Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial. Ann Hematol. 2011 Apr;90(4):379-87. doi: 10.1007/s00277-010-1090-2. Epub 2010 Oct 5.
• Background Castellsague X, Munoz N. Chapter 3: Cofactors in human papillomavirus carcinogenesis--role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr. 2003;(31):20-8.
• Background Chavez-Blanco A, Segura-Pacheco B, Perez-Cardenas E, Taja-Chayeb L, Cetina L, Candelaria M, Cantu D, Gonzalez-Fierro A, Garcia-Lopez P, Zambrano P, Perez-Plasencia C, Cabrera G, Trejo-Becerril C, Angeles E, Duenas-Gonzalez A. Histone acetylation and histone deacetylase activity of magnesium valproate in tumor and peripheral blood of patients with cervical cancer. A phase I study. Mol Cancer. 2005 Jul 7;4(1):22. doi: 10.1186/1476-4598-4-22.
• Background Choi JI, Kim SH, Seong CK, Sim JS, Lee HJ, Do KH. Recurrent uterine cervical carcinoma: spectrum of imaging findings. Korean J Radiol. 2000 Oct-Dec;1(4):198-207. doi: 10.3348/kjr.2000.1.4.198.
• Background Cull A, Cowie VJ, Farquharson DI, Livingstone JR, Smart GE, Elton RA. Early stage cervical cancer: psychosocial and sexual outcomes of treatment. Br J Cancer. 1993 Dec;68(6):1216-20. doi: 10.1038/bjc.1993.507.
• Background de Villiers EM. Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma. Int J Cancer. 2003 Mar 1;103(6):705-8. doi: 10.1002/ijc.10868.
• Background Duenas-Gonzalez A, Candelaria M, Perez-Plascencia C, Perez-Cardenas E, de la Cruz-Hernandez E, Herrera LA. Valproic acid as epigenetic cancer drug: preclinical, clinical and transcriptional effects on solid tumors. Cancer Treat Rev. 2008 May;34(3):206-22. doi: 10.1016/j.ctrv.2007.11.003. Epub 2008 Jan 15.
• Background Dueñas-Gonzalez A, Hinojosa García LM. Papel de la quimioterapia en el carcinoma cervicouterino. Rev Inst Nac Cancerol 46: 47-57, 2000.
• Background Duenas-Gonzalez A, Cetina L, Coronel J, Cervantes-Madrid D. Emerging drugs for cervical cancer. Expert Opin Emerg Drugs. 2012 Jun;17(2):203-18. doi: 10.1517/14728214.2012.683409. Epub 2012 Apr 25.
• Background Duenas-Gonzalez A, Cetina L, Coronel J, Martinez-Banos D. Pharmacotherapy options for locally advanced and advanced cervical cancer. Drugs. 2010 Mar 5;70(4):403-32. doi: 10.2165/11534370-000000000-00000.
• Background Fayers P, Bottomley A; EORTC Quality of Life Group; Quality of Life Unit. Quality of life research within the EORTC-the EORTC QLQ-C30. European Organisation for Research and Treatment of Cancer. Eur J Cancer. 2002 Mar;38 Suppl 4:S125-33. doi: 10.1016/s0959-8049(01)00448-8.
• Background Flores YN, Bishai DM, Shah KV, Lazcano-Ponce E, Lorincz A, Hernandez M, Ferris D, Salmeron J. Risk factors for cervical cancer among HPV positive women in Mexico. Salud Publica Mex. 2008 Jan-Feb;50(1):49-58. doi: 10.1590/s0036-36342008000100011.
• Background Insinga RP, Perez G, Wheeler CM, Koutsky LA, Garland SM, Leodolter S, Joura EA, Ferris DG, Steben M, Hernandez-Avila M, Brown DR, Elbasha E, Munoz N, Paavonen J, Haupt RM; FUTURE I Investigators. Incident cervical HPV infections in young women: transition probabilities for CIN and infection clearance. Cancer Epidemiol Biomarkers Prev. 2011 Feb;20(2):287-96. doi: 10.1158/1055-9965.EPI-10-0791.
• Background Friedlander M, Grogan M; U.S. Preventative Services Task Force. Guidelines for the treatment of recurrent and metastatic cervical cancer. Oncologist. 2002;7(4):342-7.
• Background Goncalves A, Fabbro M, Lhomme C, Gladieff L, Extra JM, Floquet A, Chaigneau L, Carrasco AT, Viens P. A phase II trial to evaluate gefitinib as second- or third-line treatment in patients with recurring locoregionally advanced or metastatic cervical cancer. Gynecol Oncol. 2008 Jan;108(1):42-6. doi: 10.1016/j.ygyno.2007.07.057. Epub 2007 Nov 5.
• Background Gonzalez-Fierro A, Vasquez-Bahena D, Taja-Chayeb L, Vidal S, Trejo-Becerril C, Perez-Cardenas E, de la Cruz-Hernandez E, Chavez-Blanco A, Gutierrez O, Rodriguez D, Fernandez Z, Duenas-Gonzalez A. Pharmacokinetics of hydralazine, an antihypertensive and DNA-demethylating agent, using controlled-release formulations designed for use in dosing schedules based on the acetylator phenotype. Int J Clin Pharmacol Ther. 2011 Aug;49(8):519-24. doi: 10.5414/cp201526.
• Background Holzner B, Kemmler G, Sperner-Unterweger B, Kopp M, Dunser M, Margreiter R, Marschitz I, Nachbaur D, Fleischhacker WW, Greil R. Quality of life measurement in oncology--a matter of the assessment instrument? Eur J Cancer. 2001 Dec;37(18):2349-56. doi: 10.1016/s0959-8049(01)00307-0.
• Background Jayasekara H, Rajapaksa LC, Greimel ER. The EORTC QLQ-CX24 cervical cancer-specific quality of life questionnaire: psychometric properties in a South Asian sample of cervical cancer patients. Psychooncology. 2008 Oct;17(10):1053-7. doi: 10.1002/pon.1310.
• Background Jit M, Gay N, Soldan K, Hong Choi Y, Edmunds WJ. Estimating progression rates for human papillomavirus infection from epidemiological data. Med Decis Making. 2010 Jan-Feb;30(1):84-98. doi: 10.1177/0272989X09336140. Epub 2009 Jun 12.
• Background Kitagawa R, Katsumata N, Ando M, Shimizu C, Fujiwara Y, Yoshikawa H, Satoh T, Nakanishi T, Ushijima K, Kamura T. A multi-institutional phase II trial of paclitaxel and carboplatin in the treatment of advanced or recurrent cervical cancer. Gynecol Oncol. 2012 May;125(2):307-11. doi: 10.1016/j.ygyno.2012.02.009. Epub 2012 Feb 12.
• Background Klee M, Thranov I, Machin D. Life after radiotherapy: the psychological and social effects experienced by women treated for advanced stages of cervical cancer. Gynecol Oncol. 2000 Jan;76(1):5-13. doi: 10.1006/gyno.1999.5644.
• Background Kurtz JE, Hardy-Bessard AC, Deslandres M, Lavau-Denes S, Largillier R, Roemer-Becuwe C, Weber B, Guillemet C, Paraiso D, Pujade-Lauraine E. Cetuximab, topotecan and cisplatin for the treatment of advanced cervical cancer: A phase II GINECO trial. Gynecol Oncol. 2009 Apr;113(1):16-20. doi: 10.1016/j.ygyno.2008.12.040. Epub 2009 Feb 15.
• Background Lazcano-Ponce E, Herrero R, Munoz N, Cruz A, Shah KV, Alonso P, Hernandez P, Salmeron J, Hernandez M. Epidemiology of HPV infection among Mexican women with normal cervical cytology. Int J Cancer. 2001 Feb 1;91(3):412-20. doi: 10.1002/1097-0215(20010201)91:33.0.co;2-m.
• Background Lee JS, Kim HS, Park JT, Lee MC, Park CS. Expression of vascular endothelial growth factor in the progression of cervical neoplasia and its relation to angiogenesis and p53 status. Anal Quant Cytol Histol. 2003 Dec;25(6):303-11.
• Background Lee SL, Tameru AM. A Mathematical Model of Human Papillomavirus (HPV) in the United States and its Impact on Cervical Cancer. J Cancer. 2012;3:262-8. doi: 10.7150/jca.4161. Epub 2012 Jun 9.
• Background Long HJ 3rd, Bundy BN, Grendys EC Jr, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV; Gynecologic Oncology Group Study. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20;23(21):4626-33. doi: 10.1200/JCO.2005.10.021. Epub 2005 May 23.
• Background Louie KS, Castellsague X, de Sanjose S, Herrero R, Meijer CJ, Shah K, Munoz N, Bosch FX; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Smoking and passive smoking in cervical cancer risk: pooled analysis of couples from the IARC multicentric case-control studies. Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1379-90. doi: 10.1158/1055-9965.EPI-11-0284. Epub 2011 May 24.
• Background Mani S, Herceg Z. DNA demethylating agents and epigenetic therapy of cancer. Adv Genet. 2010;70:327-40. doi: 10.1016/B978-0-12-380866-0.60012-5.
• Background Mohar A, Frias-Mendivil M. Epidemiology of cervical cancer. Cancer Invest. 2000;18(6):584-90. doi: 10.3109/07357900009012198. No abstract available.
• Background Monk BJ, Mas Lopez L, Zarba JJ, Oaknin A, Tarpin C, Termrungruanglert W, Alber JA, Ding J, Stutts MW, Pandite LN. Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer. J Clin Oncol. 2010 Aug 1;28(22):3562-9. doi: 10.1200/JCO.2009.26.9571. Epub 2010 Jul 6.
• Background Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. doi: 10.1200/JCO.2008.18.9043. Epub 2009 Jan 12.
• Background Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1;27(28):4649-55. doi: 10.1200/JCO.2009.21.8909. Epub 2009 Aug 31.
• Background Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. doi: 10.1200/JCO.2004.04.170.
• Background Moore KN, Herzog TJ, Lewin S, Giuntoli RL, Armstrong DK, Rocconi RP, Spannuth WA, Gold MA. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol. 2007 May;105(2):299-303. doi: 10.1016/j.ygyno.2006.12.031. Epub 2007 Feb 14.
• Background Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6;348(6):518-27. doi: 10.1056/NEJMoa021641.
• Background Munoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS, Shah KV, Meijer CJ, Bosch FX; International Agency for Research on Cancer. Multicentric Cervical Cancer Study Group. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet. 2002 Mar 30;359(9312):1093-101. doi: 10.1016/S0140-6736(02)08151-5.
• Background Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. doi: 10.1200/JCO.2003.02.153. Epub 2003 Jul 14.
• Background Palacio-Mejia LS, Rangel-Gomez G, Hernandez-Avila M, Lazcano-Ponce E. Cervical cancer, a disease of poverty: mortality differences between urban and rural areas in Mexico. Salud Publica Mex. 2003;45 Suppl 3:S315-25. doi: 10.1590/s0036-36342003000900005.
• Background Peiretti M, Zapardiel I, Zanagnolo V, Landoni F, Morrow CP, Maggioni A. Management of recurrent cervical cancer: a review of the literature. Surg Oncol. 2012 Jun;21(2):e59-66. doi: 10.1016/j.suronc.2011.12.008. Epub 2012 Jan 14.
• Background Sanchez-Barriga JJ. [Mortality trends from cervical cancer in the seven socioeconomic regions and the thirty two federative entities of Mexico, 2000-2008]. Gac Med Mex. 2012 Jan-Feb;148(1):42-51. Spanish.
• Background Pectasides D, Fountzilas G, Papaxoinis G, Pectasides E, Xiros N, Sykiotis C, Koumarianou A, Psyrri A, Panayiotides J, Economopoulos T. Carboplatin and paclitaxel in metastatic or recurrent cervical cancer. Int J Gynecol Cancer. 2009 May;19(4):777-81. doi: 10.1111/IGC.0b013e3181a40a8b.
• Background Omura GA, Blessing JA, Vaccarello L, Berman ML, Clarke-Pearson DL, Mutch DG, Anderson B. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1997 Jan;15(1):165-71. doi: 10.1200/JCO.1997.15.1.165.
• Background Lewis MJ. Análisis de la situación del cáncer cervicouterino en América Latina y el Caribe. Washington, D.C. Organización Panamericana de la Salud / Organización Mundial de la Salud (OPS/OMS); 2004:40.
• Background Santin AD, Sill MW, McMeekin DS, Leitao MM Jr, Brown J, Sutton GP, Van Le L, Griffin P, Boardman CH. Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Sep;122(3):495-500. doi: 10.1016/j.ygyno.2011.05.040.
• Background Schilder RJ, Sill MW, Lee YC, Mannel R. A phase II trial of erlotinib in recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study. Int J Gynecol Cancer. 2009 Jul;19(5):929-33. doi: 10.1111/IGC.0b013e3181a83467.
• Background Sit AS, Kelley JL, Gallion HH, Kunschner AJ, Edwards RP. Paclitaxel and carboplatin for recurrent or persistent cancer of the cervix. Cancer Invest. 2004;22(3):368-73. doi: 10.1081/cnv-200029062.
• Background Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Peto J, Plummer M, Franceschi S, Beral V. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet. 2003 Apr 5;361(9364):1159-67. doi: 10.1016/s0140-6736(03)12949-2.
• Background Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. doi: 10.1056/NEJMoa1309748.
• Background Tinker AV, Bhagat K, Swenerton KD, Hoskins PJ. Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Gynecol Oncol. 2005 Jul;98(1):54-8. doi: 10.1016/j.ygyno.2005.03.037.
• Background Vaccarella S, Herrero R, Dai M, Snijders PJ, Meijer CJ, Thomas JO, Hoang Anh PT, Ferreccio C, Matos E, Posso H, de Sanjose S, Shin HR, Sukvirach S, Lazcano-Ponce E, Ronco G, Rajkumar R, Qiao YL, Munoz N, Franceschi S. Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys. Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2148-53. doi: 10.1158/1055-9965.EPI-06-0556.
• Background Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9. doi: 10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-F.
• Background Wright JD, Viviano D, Powell MA, Gibb RK, Mutch DG, Grigsby PW, Rader JS. Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer. Gynecol Oncol. 2006 Nov;103(2):489-93. doi: 10.1016/j.ygyno.2006.03.023. Epub 2006 May 2.
• Background Zagouri F, Sergentanis TN, Chrysikos D, Filipits M, Bartsch R. Molecularly targeted therapies in cervical cancer. A systematic review. Gynecol Oncol. 2012 Aug;126(2):291-303. doi: 10.1016/j.ygyno.2012.04.007. Epub 2012 Apr 11.
• Background Zambrano P, Segura-Pacheco B, Perez-Cardenas E, Cetina L, Revilla-Vazquez A, Taja-Chayeb L, Chavez-Blanco A, Angeles E, Cabrera G, Sandoval K, Trejo-Becerril C, Chanona-Vilchis J, Duenas-Gonzalez A. A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes. BMC Cancer. 2005 Apr 29;5:44. doi: 10.1186/1471-2407-5-44.

Drugs

Indications