Phase 1/2a Evaluation of AL3818 in Subjects With Recurrent or Metastatic Endometrial, Ovarian or Cervical Cancer (AL3818-US-001)

Summary

The purpose of Part 1 (Phase 1b) is to evaluate the general safety and tolerability of repeated 21-day cycles of AL3818 therapy, and to reevaluate the maximum tolerated dose (MTD). The purpose of Part 2 (Phase 2a) is to evaluate the efficacy of repeated 21-day cycles of AL3818 therapy preliminary efficacy of AL3818 in subjects with recurrent or metastatic endometrial, ovarian or cervical cancer.

Timeline

Start

2015-11

Primary completion

2017-02-14

Completion

2017-05-30

Publications

• Background Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 2010 Aug;11(8):1000-17. doi: 10.2174/138945010791591395.
• Background Roskoski R Jr. Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 2007 Jun;62(3):179-213. doi: 10.1016/j.critrevonc.2007.01.006. Epub 2007 Feb 26.
• Background Dickson C, Spencer-Dene B, Dillon C, Fantl V. Tyrosine kinase signalling in breast cancer: fibroblast growth factors and their receptors. Breast Cancer Res. 2000;2(3):191-6. doi: 10.1186/bcr53. Epub 2000 Mar 25.
• Background Cole C, Lau S, Backen A, Clamp A, Rushton G, Dive C, Hodgkinson C, McVey R, Kitchener H, Jayson GC. Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer. Cancer Biol Ther. 2010 Sep 1;10(5):495-504. doi: 10.4161/cbt.10.5.12585. Epub 2010 Sep 4.
• Background Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80. doi: 10.1124/pr.56.4.3.
• Background Kondo Y, Arii S, Mori A, Furutani M, Chiba T, Imamura M. Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line. Clin Cancer Res. 2000 Feb;6(2):622-30.
• Background Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, Reventos J, Palacios J, Prat J, Matias-Guiu X. Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene. 2013 Jan 24;32(4):403-13. doi: 10.1038/onc.2012.76. Epub 2012 Mar 19.
• Background Byron SA, Loch DC, Pollock PM. Fibroblast growth factor receptor inhibition synergizes with Paclitaxel and Doxorubicin in endometrial cancer cells. Int J Gynecol Cancer. 2012 Nov;22(9):1517-26. doi: 10.1097/IGC.0b013e31826f6806.
• Background Gorringe KL, Jacobs S, Thompson ER, Sridhar A, Qiu W, Choong DY, Campbell IG. High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications. Clin Cancer Res. 2007 Aug 15;13(16):4731-9. doi: 10.1158/1078-0432.CCR-07-0502.
• Background Christensen C, Lauridsen JB, Berezin V, Bock E, Kiselyov VV. The neural cell adhesion molecule binds to fibroblast growth factor receptor 2. FEBS Lett. 2006 Jun 12;580(14):3386-90. doi: 10.1016/j.febslet.2006.05.008. Epub 2006 May 11.
• Background Byron SA, Gartside MG, Wellens CL, Goodfellow PJ, Birrer MJ, Campbell IG, Pollock PM. FGFR2 mutations are rare across histologic subtypes of ovarian cancer. Gynecol Oncol. 2010 Apr;117(1):125-9. doi: 10.1016/j.ygyno.2009.12.002. Epub 2010 Jan 27.
• Background Taniguchi F, Itamochi H, Harada T, Terakawa N. Fibroblast growth factor receptor 2 expression may be involved in transformation of ovarian endometrioma to clear cell carcinoma of the ovary. Int J Gynecol Cancer. 2013 Jun;23(5):791-6. doi: 10.1097/IGC.0b013e31828f38c4.
• Background Tsang TY, Mohapatral G, Itamochi H, Mok SC, and Birrer MJ., Abstract 1528: Identification of FGFR3 as a potential therapeutic target gene for human clear cell ovarian cancer by global genomic analysis. Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA
• Background Kawase R, Ishiwata T, Matsuda Y, Onda M, Kudo M, Takeshita T, Naito Z. Expression of fibroblast growth factor receptor 2 IIIc in human uterine cervical intraepithelial neoplasia and cervical cancer. Int J Oncol. 2010 Feb;36(2):331-40.

Drugs

Indications