Bortezomib Plus Cisplatin in Recurrent or Metastatic Breast Cancer

Summary

This a phase 1 study to evaluate the safety and preliminary efficacy of cisplatin combined with bortezomib in patients with recurrent or metastatic breast cancer.

Timeline

Start

2025-01-01

Primary completion

2026-06-30

Completion

2028-06-30

Publications

• Background Shao F, Lyu X, Miao K, Xie L, Wang H, Xiao H, Li J, Chen Q, Ding R, Chen P, Xing F, Zhang X, Luo GH, Zhu W, Cheng G, Lon NW, Martin SE, Wang G, Chen G, Dai Y, Deng CX. Enhanced Protein Damage Clearance Induces Broad Drug Resistance in Multitype of Cancers Revealed by an Evolution Drug-Resistant Model and Genome-Wide siRNA Screening. Adv Sci (Weinh). 2020 Oct 11;7(23):2001914. doi: 10.1002/advs.202001914. eCollection 2020 Dec.
• Background Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017 Jul;14(7):417-433. doi: 10.1038/nrclinonc.2016.206. Epub 2017 Jan 24.
• Background Irvin WJ Jr, Orlowski RZ, Chiu WK, Carey LA, Collichio FA, Bernard PS, Stijleman IJ, Perou C, Ivanova A, Dees EC. Phase II study of bortezomib and pegylated liposomal doxorubicin in the treatment of metastatic breast cancer. Clin Breast Cancer. 2010 Dec 1;10(6):465-70. doi: 10.3816/CBC.2010.n.061.
• Background Engel RH, Brown JA, Von Roenn JH, O'Regan RM, Bergan R, Badve S, Rademaker A, Gradishar WJ. A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience. Cancer Invest. 2007 Dec;25(8):733-7. doi: 10.1080/07357900701506573. Epub 2007 Oct 18.
• Background Thaler S, Thiede G, Hengstler JG, Schad A, Schmidt M, Sleeman JP. The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen receptor-positive breast cancer. Int J Cancer. 2015 Aug 1;137(3):686-97. doi: 10.1002/ijc.29404. Epub 2015 Jan 8.
• Background Mack PC, Davies AM, Lara PN, Gumerlock PH, Gandara DR. Integration of the proteasome inhibitor PS-341 (Velcade) into the therapeutic approach to lung cancer. Lung Cancer. 2003 Aug;41 Suppl 1:S89-96. doi: 10.1016/s0169-5002(03)00149-1.
• Background Ikezoe T, Yang Y, Saito T, Koeffler HP, Taguchi H. Proteasome inhibitor PS-341 down-regulates prostate-specific antigen (PSA) and induces growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells. Cancer Sci. 2004 Mar;95(3):271-5. doi: 10.1111/j.1349-7006.2004.tb02215.x.
• Background Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999 Jun 1;59(11):2615-22.
• Background Pharoah PD, Day NE, Caldas C. Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer. 1999 Aug;80(12):1968-73. doi: 10.1038/sj.bjc.6690628.
• Background Osin PP, Lakhani SR. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis. Breast Cancer Res. 1999;1(1):36-40. doi: 10.1186/bcr11. Epub 1999 Oct 27.
• Background Orlowski RZ, Dees EC. The role of the ubiquitination-proteasome pathway in breast cancer: applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer. Breast Cancer Res. 2003;5(1):1-7. doi: 10.1186/bcr460. Epub 2002 Aug 14.
• Background Boccadoro M, Morgan G, Cavenagh J. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005 Jun 1;5(1):18. doi: 10.1186/1475-2867-5-18.
• Background Lenz HJ. Clinical update: proteasome inhibitors in solid tumors. Cancer Treat Rev. 2003 May;29 Suppl 1:41-8. doi: 10.1016/s0305-7372(03)00082-3.
• Background Cusack JC. Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cancer Treat Rev. 2003 May;29 Suppl 1:21-31. doi: 10.1016/s0305-7372(03)00079-3.
• Background Adams J. Development of the proteasome inhibitor PS-341. Oncologist. 2002;7(1):9-16. doi: 10.1634/theoncologist.7-1-9.
• Background Kane RC, Farrell AT, Sridhara R, Pazdur R. United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin Cancer Res. 2006 May 15;12(10):2955-60. doi: 10.1158/1078-0432.CCR-06-0170.
• Background Awada A, Albanell J, Canney PA, Dirix LY, Gil T, Cardoso F, Gascon P, Piccart MJ, Baselga J. Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study. Br J Cancer. 2008 May 6;98(9):1500-7. doi: 10.1038/sj.bjc.6604347. Epub 2008 Apr 29.

Drugs

Indications