April 2012

July 2007 clinical trial update

Five clinical trials were added this month:

AB1010 Phase II

AB1010 or masitinib manufactured by AB Science in France is in Phase II. Dr Axel Le Cesne at Institut Gustave- Roussy in Villejuif, France is the Primary Investigator. Masitinib is a c-Kit/ PDGFRa inhibitor similar to imatinib. This trial continues to be available mainly to patients in France.

MP470 Phase I

MP470 is a multi-targeted tyrosine kinase inhibitor that appears effective in the lab against multiple c-kit mutations resistant to imatinib. MP470 appears to also be an inhibitor of alternate signaling pathways that may take over when c-Kit is blocked by targeted therapy. Lab tests in GIST cell lines have shown that AXL and c-Met pathways are sometimes activated and may be a mechanism of resistance to Gleevec. Contacts at SuperGen have indicated that trials are expected to start soon at two locations: Johns Hopkins University, Baltimore, Md. under Manual Hidalgo and Wells Messersmith and at the University of Arizona in Scottsdale, Ariz. under Dan Von Hoff.

AMN107 Phase III

The AMN107 Phase III trial is now open at three sites in the U.S. Fox Chase in Philadelphia, Pa., Dana Farber in Boston, Mass. and Washington University in St. Louis, Mo. Ten sites in total are planned in the U.S. Four are planned in Canada. Four sites are open in Europe. One site each is open in Taiwan and Australia. Patients must have had only Gleevec and Sutent to be eligible for this trial. Novartis continues to make AMN107 available through a compassionate access program. Novartis tells us that over 140 patients have been approved under this program worldwide. Plans are also underway for a second AMN107 trial in the U.S. that will admit patients now excluded because of prior molecular therapy. The protocol is now under review at a clinical trial site and the trial should open within the next six months.

KOS1022 Phase I

This drug by Kosan is a Heat Shock Protein (HSP90) inhibitor. It is designed to inhibit the chaperone protein that protects mutant c-Kit. This enables the cell to destroy the mutant c-Kit. KOS1022 is a second generation HSP90 inhibitor designed to be taken orally. This Phase I trial admits patients with advanced solid tumors and is not exclusive to GIST.

Imatinib or sunitinib Phase III

This trial is now recruiting GIST patients. Patients experiencing progression at 400 mg of imatinib are offered either 800 mg daily of imatinib or 37.5 mg daily of sunitinib.

To view the latest clinical trials, visit: http://www.liferaftgroup.org/docs/gist_clinical_trial_datasheets.htm.htm