September 2006 clinical trial update

By Jerry Call

Sutent

In the United States, Canada and the United Kingdom, Sutent is now approved for patients failing Gleevec or those who cannot tolerate Gleevec. In addition, Sutent continues to be available to patients via the “Treatment Use Protocol,” which is ‘four weeks on/two weeks off’ (50 mg). There are many sites open throughout the world. Site information changes frequently; for the most current information, contact EmergingMed at 1-877- 416-6248 (outside the United States) or at 1-800-620-6104 (inside the United States). If international patients have problems with the listed number, use email at: sutent@emeringmed.com.

The phase II trial testing Sutent given on a continuous basis has met its accrual goals and is now closed.

AMN107 + Gleevec

This Phase I trial is open but undergoes fairly frequent start/stop periods as cohorts accrue. Contact the trial centers for current information.

The U.S. sites are:
• Dr. Demetri in Dana-Farber Cancer Institute in Boston, Massachusetts.
• Dr. von Mehren in Fox-Chase Cancer Center in Philadelphia, Pennsylvania.

International trial sites include:
• Dr. Patrick Schöffski in Leuven, Belgium
• Dr. Jean-Yves Blay in Lyon, France
• Dr. Peter Reichardt in Berlin, Germany
• Dr. Paolo Giovanni Casali in Milan, Italy

The current intention is to evaluate doses as high as 800 mg of AMN107 and 400 mg of Gleevec. A total of about 45 patients are expected to be enrolled in the phase I trial and 200 to 300 patients are expected for the phase II trial. The phase II portion of the trial is projected to start this fall.

The combination of AMN107 and Gleevec may have a broad spectrum of activity against primary and secondary mutations in GIST. The generic name for AMN107 is nilotinib and our understanding is that the brand name will be Tasigna.

IPI-504

The IPI-504 phase I trial is open and accruing patients at Dana-Farber. IPI- 504 is an inhibitor of Heat Shock Protein 90 (HSP90) and has been the subject of articles in the November 2005 and January 2006 editions of the Life Raft Group newsletter. This is an intravenous drug which is administered twice a week for two weeks followed by a one week off period.

Genasense + Gleevec

A phase II trial testing the combination of Genasense plus Gleevec in patients with Gleevec-resistant GIST recently opened. Genasense (Genta Inc.) is an antisense drug that inhibits bcl-2. Bcl-2 is a protein involved in cellular survival.

This drug is administered intravenously. It is hoped that Genasense may help Gleevec kill tumor cells by making them more sensitive to Gleevec. This trial is currently open only at M.D. Anderson.

Several other trial sites are planned including: Dana-Farber Cancer Institute, Boston, Massachusetts; University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan; Mayo Clinic Cancer Center, Rochester, Minnesota; and Memorial Sloan-Kettering Cancer Center, New York, New York.

Perifosine + Gleevec

Perifosine is an oral drug that inhibits the AKT protein. AKT is an antiapoptosis protein. It is speculated that inhibition of AKT might enhance therapy. Apoptosis is a form of controlled cell death, a type of cellular suicide where the cell issues its own death warrant. The phase II trial, which combines Perifosine with Gleevec is open at M.D. Anderson Cancer Center and accruing Gleevec-resistant GIST patients.

RAD001 + Gleevec

Both RAD001 and Gleevec are manufactured by Novartis. RAD001 is an mTOR inhibitor that may improve the effectiveness of Gleevec The phase 2 portion of the trial is completing its stage I enrollment; the decision to expand the trial will be made in the coming months. Additional sites are being opened in anticipation of the future work.

Current sites are: Dana-Farber (Boston); Berlin, Germany; and the University of California (Los Angeles). Fox Chase Cancer Center in Philadelphia is expected to open soon.

PTK787/ZK222584

This is a phase II study being conducted at the University of Helsinki in Finland and in Milan, Italy. PTK787/ ZK222584 was synthesized and developed by Novartis Pharma AG and Schering AG. It is a tyrosine kinase inhibitor and inhibits VEGF receptors as well as KIT and PDGFRB. See the July 2006 Life Raft Group newsletter for an article about this trial.

BMS-354825 (Dasatinib)

BMS-354825 is a tyrosine kinase inhibitor of Src, abl, KIT, and PDGFR. Dasatinib is available in a phase I trial at Dana-Farber and Glasgow, Scotland. Future plans include a SARC phase II trial. We will update trial sites and the scope of the trial as this information becomes available.

BAY 43-9006 (known as Sorafenib and by trade name Nexavar)

This drug was approved in December 2005 for kidney cancer. BAY 43-9006 inhibits several kinases including KIT, VEGFR-2, VEGFR-3, PDGRF-β, RAF, FLT3, and RET. The phase II trial for BAY 43-9006 is open and recruiting patients.

Three trial sites are open in Illinois and one in New York:
• University of Chicago- Chicago, Illinois.
• Decatur Memorial Hospital- Decatur, Illinois.
• Oncology/Hematology Associates of Central Illinois- Peoria, Illinois.
• Memorial Sloan-Kettering Cancer Center-New York, New York.