Efficacy of Letrozole in Recurrent Ovarian Cancer

Summary

Randomized phase III multicenter study investigating the role of letrozole in heavily pretreated recurrent ovarian cancer.

Timeline

Start

2020-06-22

Primary completion

2024-11-01

Completion

2024-11-04

Outcome

Outcome not reported

Stopped: “Logistical problems impacting the speed of enrolment”

Publications

• Background Banerjee S, Kaye SB, Ashworth A. Making the best of PARP inhibitors in ovarian cancer. Nat Rev Clin Oncol. 2010 Sep;7(9):508-19. doi: 10.1038/nrclinonc.2010.116. Epub 2010 Aug 10.
• Background Banerjee S, Kaye SB. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin Cancer Res. 2013 Mar 1;19(5):961-8. doi: 10.1158/1078-0432.CCR-12-2243. Epub 2013 Jan 10.
• Background Gore ME, Fryatt I, Wiltshaw E, Dawson T. Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecol Oncol. 1990 Feb;36(2):207-11. doi: 10.1016/0090-8258(90)90174-j.
• Background Markman M, Rothman R, Hakes T, Reichman B, Hoskins W, Rubin S, Jones W, Almadrones L, Lewis JL Jr. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 1991 Mar;9(3):389-93. doi: 10.1200/JCO.1991.9.3.389.
• Background Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, Fossati R, Ravaioli A, Mangioni C. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and I.O.R. (Istituto Oncologico Romagnolo) group. Br J Cancer. 2004 Jun 1;90(11):2112-7. doi: 10.1038/sj.bjc.6601787.
• Background Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P, Stauch M, Paulenz A, Camara O, Keil E, Lichtenegger W. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2008 Jul 1;26(19):3176-82. doi: 10.1200/JCO.2007.15.1258.
• Background ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmstrom H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. doi: 10.1200/JCO.1997.15.6.2183.
• Background Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. doi: 10.1200/JCO.2001.19.14.3312.
• Background Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. doi: 10.1200/JCO.2006.09.6735.
• Background Vergote I, Finkler NJ, Hall JB, Melnyk O, Edwards RP, Jones M, Keck JG, Meng L, Brown GL, Rankin EM, Burke JJ, Boccia RV, Runowicz CD, Rose PG. Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2010 Jul;20(5):772-80. doi: 10.1111/igc.0b013e3181daaf59.
• Background Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. doi: 10.1200/JCO.2013.51.4489. Epub 2014 Mar 17.
• Background Lakusta CM, Atkinson MJ, Robinson JW, Nation J, Taenzer PA, Campo MG. Quality of life in ovarian cancer patients receiving chemotherapy. Gynecol Oncol. 2001 Jun;81(3):490-5. doi: 10.1006/gyno.2001.6199.
• Background Demers LM, Melby JC, Wilson TE, Lipton A, Harvey HA, Santen RJ. The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis. J Clin Endocrinol Metab. 1990 Apr;70(4):1162-6.
• Background Lipton A, Demers LM, Harvey HA, Kambic KB, Grossberg H, Brady C, Adlercruetz H, Trunet PF, Santen RJ. Letrozole (CGS 20267). A phase I study of a new potent oral aromatase inhibitor of breast cancer. Cancer. 1995 Apr 15;75(8):2132-8. doi: 10.1002/1097-0142(19950415)75:83.0.co;2-u.
• Background El Ouagari K, Karnon J, Delea T, Talbot W, Brandman J. Cost-effectiveness of letrozole in the extended adjuvant treatment of women with early breast cancer. Breast Cancer Res Treat. 2007 Jan;101(1):37-49. doi: 10.1007/s10549-006-9262-4. Epub 2006 Jul 4.
• Background Sioufi A, Gauducheau N, Pineau V, Marfil F, Jaouen A, Cardot JM, Godbillon J, Czendlik C, Howald H, Pfister C, Vreeland F. Absolute bioavailability of letrozole in healthy postmenopausal women. Biopharm Drug Dispos. 1997 Dec;18(9):779-89. doi: 10.1002/(sici)1099-081x(199712)18:93.0.co;2-5.
• Background Sioufi A, Sandrenan N, Godbillon J, Trunet P, Czendlik C, Howald H, Pfister C, Ezzet F. Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5 mg single oral administration. Biopharm Drug Dispos. 1997 Aug;18(6):489-97. doi: 10.1002/(sici)1099-081x(199708)18:63.0.co;2-p.
• Background Dave N, Gudelsky GA, Desai PB. The pharmacokinetics of letrozole in brain and brain tumor in rats with orthotopically implanted C6 glioma, assessed using intracerebral microdialysis. Cancer Chemother Pharmacol. 2013 Aug;72(2):349-57. doi: 10.1007/s00280-013-2205-y. Epub 2013 Jun 9.
• Background Lamb HM, Adkins JC. Letrozole. A review of its use in postmenopausal women with advanced breast cancer. Drugs. 1998 Dec;56(6):1125-40. doi: 10.2165/00003495-199856060-00020.
• Background Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. doi: 10.1056/NEJMoa032312. Epub 2003 Oct 9.
• Background Batra S, Iosif CS. Elevated concentrations of antiestrogen binding sites in membrane fractions of human ovarian tumors. Gynecol Oncol. 1996 Feb;60(2):228-32. doi: 10.1006/gyno.1996.0030.
• Background Langdon SP, Gourley C, Gabra H, Stanley B. Endocrine therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2017 Feb;17(2):109-117. doi: 10.1080/14737140.2017.1272414. Epub 2016 Dec 24.
• Background Slotman BJ, Rao BR. Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy. Anticancer Res. 1988 May-Jun;8(3):417-34.
• Background Langdon SP, Hawkes MM, Lawrie SS, Hawkins RA, Tesdale AL, Crew AJ, Miller WR, Smyth JF. Oestrogen receptor expression and the effects of oestrogen and tamoxifen on the growth of human ovarian carcinoma cell lines. Br J Cancer. 1990 Aug;62(2):213-6. doi: 10.1038/bjc.1990.263.
• Background Langdon SP, Crew AJ, Ritchie AA, Muir M, Wakeling A, Smyth JF, Miller WR. Growth inhibition of oestrogen receptor-positive human ovarian carcinoma by anti-oestrogens in vitro and in a xenograft model. Eur J Cancer. 1994;30A(5):682-6. doi: 10.1016/0959-8049(94)90545-2.
• Background O'Donnell AJ, Macleod KG, Burns DJ, Smyth JF, Langdon SP. Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. Endocr Relat Cancer. 2005 Dec;12(4):851-66. doi: 10.1677/erc.1.01039.
• Background Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
• Background Papadimitriou CA, Markaki S, Siapkaras J, Vlachos G, Efstathiou E, Grimani I, Hamilos G, Zorzou M, Dimopoulos MA. Hormonal therapy with letrozole for relapsed epithelial ovarian cancer. Long-term results of a phase II study. Oncology. 2004;66(2):112-7. doi: 10.1159/000077436.
• Background Bowman A, Gabra H, Langdon SP, Lessells A, Stewart M, Young A, Smyth JF. CA125 response is associated with estrogen receptor expression in a phase II trial of letrozole in ovarian cancer: identification of an endocrine-sensitive subgroup. Clin Cancer Res. 2002 Jul;8(7):2233-9.
• Background Markman M, Iseminger KA, Hatch KD, Creasman WT, Barnes W, Dubeshter B. Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report. Gynecol Oncol. 1996 Jul;62(1):4-6. doi: 10.1006/gyno.1996.0181.
• Background Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. doi: 10.1200/JCO.2007.13.6606.
• Background Le T, Leis A, Pahwa P, Wright K, Ali K, Reeder B, Kinderchuck M, Ward K. Quality of life evaluations of caregivers of ovarian cancer patients during chemotherapy treatment. J Obstet Gynaecol Can. 2004 Jul;26(7):627-31. doi: 10.1016/s1701-2163(16)30609-0.
• Background Stiggelbout AM, de Haes JC. Patient preference for cancer therapy: an overview of measurement approaches. J Clin Oncol. 2001 Jan 1;19(1):220-30. doi: 10.1200/JCO.2001.19.1.220.

Drugs

Indications