Cabazitaxel Activity in Patients With Advanced AdrenoCortical-Carcinoma Progressing After Previous Chemotherapy Lines

Summary

Adrenocortical cancer (ACC) is a rare aggressive tumor. The treatment of metastatic ACC is challenging and the current available treatments are mitotane, chemotherapy or the combination of both. Prognosis in locally advanced inoperable and metastatic ACC patients still remains poor, the 5-year overall survival being \<15%. New treatment strategies are therefore needed. The taxanes are a class of drugs targeting the microtubules that have shown to be effective in the treatment of several malignancies but have not been fully developed in patients with ACC. Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel. Cabazitaxel was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. The activity of the drug against several malignancies is currently tested in ongoing prospective studies, but to our knowledge neither preclinical nor clinical studies are currently testing cabaztaxel in ACC. This study is aimed to demonstrate that cabazitaxel is active in ACC, but the drug was never tested before in this clinical setting. A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC. The phase II study will be conducted in 2 different Italian Institutions that are reference centers for ACC.

Timeline

Start

2018-01-25

Primary completion

2021-01-24

Completion

2022-01-24

Publications

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• Results Mita AC, Figlin R, Mita MM. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer? Clin Cancer Res. 2012 Dec 15;18(24):6574-9. doi: 10.1158/1078-0432.CCR-12-1584. Epub 2012 Oct 22.
• Results Montoya M, Brown JW, Fishman LM. Comparative effects of chemotherapeutic agents on the growth and survival of human adrenal carcinoma cells in culture. Horm Metab Res. 2008 May;40(5):302-5. doi: 10.1055/s-2008-1073139.
• Results Kroiss M, Quinkler M, Lutz WK, Allolio B, Fassnacht M. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011 Nov;75(5):585-91. doi: 10.1111/j.1365-2265.2011.04214.x.
• Results Hasegawa E, Nakagawa S, Sato M, Tachikawa E, Yamato S. Effect of polyphenols on production of steroid hormones from human adrenocortical NCI-H295R cells. Biol Pharm Bull. 2013;36(2):228-37. doi: 10.1248/bpb.b12-00627.
• Results Arrighi N, Bodei S, Lucente A, Michel MC, Zani D, Simeone C, Cunico SC, Spano P, Sigala S. Muscarinic receptors stimulate cell proliferation in the human urothelium-derived cell line UROtsa. Pharmacol Res. 2011 Oct;64(4):420-5. doi: 10.1016/j.phrs.2011.06.009. Epub 2011 Jun 28.
• Results 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.
• Results Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ, Carnaghi C, Casali P, Porpiglia F, Mantero F, Reimondo G, Angeli A, Dogliotti L. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657-66. doi: 10.1677/erc.1.01025.
• Lagana M, Grisanti S, Ambrosini R, Cosentini D, Abate A, Zamparini M, Ferrari VD, Gianoncelli A, Turla A, Canu L, Terzolo M, Tiberio GAM, Sigala S, Berruti A. Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma. ESMO Open. 2022 Apr;7(2):100422. doi: 10.1016/j.esmoop.2022.100422. Epub 2022 Mar 7.

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