AT13387 in Adults With Refractory Solid Tumors

Summary

Background: \- The experimental drug AT13387 has been shown to have some anticancer effects against tumor cells by blocking a protein that affects other proteins inside certain cancer cells, and helps to prevent the cancer cells from reproducing and spreading. AT13387 has not been tested in humans, and researchers are interested in investigating whether it can be used to treat solid tumors that have not responded to standard treatments. Objectives: \- To investigate the safety and effectiveness of AT13387 in individuals with solid tumors. Eligibility: \- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatments. Design: * Participants will be screened with a physical examination and medical history, as well as blood tests and tumor imaging studies. * AT13387 will be given in 28-day cycles of treatment. Participants will receive AT13387 twice a week (2 days in a row) for the first 3 weeks of the cycle, followed by a fourth week without the drug. * Participants will have regular blood and urine samples, imaging studies, eye examinations, and tumor biopsies to monitor the effects of the treatment. * Participants will continue treatment with AT13387 unless serious side effects develop or the tumor stops responding to treatment.

Timeline

Start

2010-11-19

Primary completion

2013-12-30

Completion

2017-10-27

Publications

• Background Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, Kluger HM. High HSP90 expression is associated with decreased survival in breast cancer. Cancer Res. 2007 Apr 1;67(7):2932-7. doi: 10.1158/0008-5472.CAN-06-4511.
• Background Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8. doi: 10.1073/pnas.91.18.8324.
• Background Bagatell R, Whitesell L. Altered Hsp90 function in cancer: a unique therapeutic opportunity. Mol Cancer Ther. 2004 Aug;3(8):1021-30.
• Do K, Speranza G, Chang LC, Polley EC, Bishop R, Zhu W, Trepel JB, Lee S, Lee MJ, Kinders RJ, Phillips L, Collins J, Lyons J, Jeong W, Antony R, Chen AP, Neckers L, Doroshow JH, Kummar S. Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors. Invest New Drugs. 2015 Aug;33(4):921-30. doi: 10.1007/s10637-015-0255-1. Epub 2015 Jun 18.

Drugs

Indications