Study of Minnelide™ in Patients With Advanced GI Tumors

Summary

The primary objective of this study is to determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™ and to establish the dose of Minnelide™ recommended for future phase 2 protocol

Timeline

Start

2013-08

Primary completion

2016-10

Completion

2016-12

Publications

• Background Antonoff MB, Chugh R, Borja-Cacho D, Dudeja V, Clawson KA, Skube SJ, Sorenson BS, Saltzman DA, Vickers SM, Saluja AK. Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo. Surgery. 2009 Aug;146(2):282-90. doi: 10.1016/j.surg.2009.04.023.
• Background Carter BZ, Mak DH, Schober WD, McQueen T, Harris D, Estrov Z, Evans RL, Andreeff M. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood. 2006 Jul 15;108(2):630-7. doi: 10.1182/blood-2005-09-3898. Epub 2006 Mar 23.
• Background Choi YJ, Kim TG, Kim YH, Lee SH, Kwon YK, Suh SI, Park JW, Kwon TK. Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells. Biochem Pharmacol. 2003 Jul 15;66(2):273-80. doi: 10.1016/s0006-2952(03)00282-x.
• Background Liu Q, Chen T, Chen H, Zhang M, Li N, Lu Z, Ma P, Cao X. Triptolide (PG-490) induces apoptosis of dendritic cells through sequential p38 MAP kinase phosphorylation and caspase 3 activation. Biochem Biophys Res Commun. 2004 Jul 2;319(3):980-6. doi: 10.1016/j.bbrc.2004.04.201.
• Background Phillips PA, Dudeja V, McCarroll JA, Borja-Cacho D, Dawra RK, Grizzle WE, Vickers SM, Saluja AK. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 2007 Oct 1;67(19):9407-16. doi: 10.1158/0008-5472.CAN-07-1077.
• Background Shamon LA, Pezzuto JM, Graves JM, Mehta RR, Wangcharoentrakul S, Sangsuwan R, Chaichana S, Tuchinda P, Cleason P, Reutrakul V. Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 1997 Jan 15;112(1):113-7. doi: 10.1016/S0304-3835(96)04554-5.
• Background Tengchaisri T, Chawengkirttikul R, Rachaphaew N, Reutrakul V, Sangsuwan R, Sirisinha S. Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters. Cancer Lett. 1998 Nov 27;133(2):169-75. doi: 10.1016/s0304-3835(98)00222-5.
• Background Wang X, Matta R, Shen G, Nelin LD, Pei D, Liu Y. Mechanism of triptolide-induced apoptosis: Effect on caspase activation and Bid cleavage and essentiality of the hydroxyl group of triptolide. J Mol Med (Berl). 2006 May;84(5):405-15. doi: 10.1007/s00109-005-0022-4. Epub 2005 Dec 30.
• Background Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, Yang J, Underhill CB, Zhang L. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2003 Jan;2(1):65-72.

Drugs

Indications

No indication recorded.