Arsenic Trioxide in Refractory Solid Tumors With Rescuable p53 Mutation

Summary

This study is an open, prospective, single arm, multi center exploratory basket clinical study. 20 refractory solid tumors patients with rescuable p53 mutation will be enrolled, and the efficacy and safety of arsenic trioxide in those patients will be evaluated.

Timeline

Start

2021-04-20

Primary completion

2022-04-30

Completion

2024-04-30

Publications

• Background Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30.
• Background Chen S, Wu JL, Liang Y, Tang YG, Song HX, Wu LL, Xing YF, Yan N, Li YT, Wang ZY, Xiao SJ, Lu X, Chen SJ, Lu M. Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site. Cancer Cell. 2021 Feb 8;39(2):225-239.e8. doi: 10.1016/j.ccell.2020.11.013. Epub 2020 Dec 24.
• Background Kopetz S, Desai J, Chan E, Hecht JR, O'Dwyer PJ, Maru D, Morris V, Janku F, Dasari A, Chung W, Issa JP, Gibbs P, James B, Powis G, Nolop KB, Bhattacharya S, Saltz L. Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer. J Clin Oncol. 2015 Dec 1;33(34):4032-8. doi: 10.1200/JCO.2015.63.2497. Epub 2015 Oct 12.
• Background Sabapathy K, Lane DP. Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others. Nat Rev Clin Oncol. 2018 Jan;15(1):13-30. doi: 10.1038/nrclinonc.2017.151. Epub 2017 Sep 26.
• Background Wang H, Liu Y, Wang X, Liu D, Sun Z, Wang C, Jin G, Zhang B, Yu S. Randomized clinical control study of locoregional therapy combined with arsenic trioxide for the treatment of hepatocellular carcinoma. Cancer. 2015 Sep 1;121(17):2917-25. doi: 10.1002/cncr.29456. Epub 2015 May 29.
• Background Zhang TD, Chen GQ, Wang ZG, Wang ZY, Chen SJ, Chen Z. Arsenic trioxide, a therapeutic agent for APL. Oncogene. 2001 Oct 29;20(49):7146-53. doi: 10.1038/sj.onc.1204762.
• Tang Y, Song H, Wang Z, Xiao S, Xiang X, Zhan H, Wu L, Wu J, Xing Y, Tan Y, Liang Y, Yan N, Li Y, Li J, Wu J, Zheng D, Jia Y, Chen Z, Li Y, Zhang Q, Zhang J, Zeng H, Tao W, Liu F, Wu Y, Lu M. Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. Cell Rep. 2022 Apr 12;39(2):110622. doi: 10.1016/j.celrep.2022.110622.

Drugs

Indications