U.S., Germany launch "Gleevec combo" trial

Phase II trial of PKC412 plus 600 mg Gleevec charts new territory

Combination treatments are very common in cancer therapy. It has long been speculated that adding a second drug to Gleevec might improve the results over Gleevec alone. The first of these “Gleevec combination” trials to reach phase II testing is Gleevec plus PKC412.

Phase II trials are starting in Berlin, Germany, and in Portland, Oregon, U.S.A. Lead researchers are Dr. Peter Reichardt at the Robert- Rössle-Klinik, Charité Campus Buch in Berlin, and Dr. Charles Blanke at Oregon Health & Sciences University in Portland. Jerry Call, Life Raft Group science coordinator, recently had an e-mail exchange with both researchers.

PKC412 and Gleevec are both manufactured by Novartis. Reichardt, who conducted the Phase I trial for this combination, describes PKC412:

“PKC412 is an inhibitor of protein kinase C (PKC). The PKC family consists of at least 12 isoforms of serine/threonine kinases that play a major role in signal transduction. It has been shown that PKC inhibitors can also reduce tumor angiogenesis. PKC412 is a very active and more selective derivative of the PKCinhibitor staurosporine.”

Reichardt describes the reason for using PKC412 in combination with Gleevec.

“The main reason for combination is that even in progressive GIST, many of the tumor cells are still under control of Gleevec. If Gleevec is stopped, a much faster progression can result. This has been seen in patients.”

Blanke was one of three U.S. doctors who conducted the phase II trials of Gleevec for GIST.

This phase II trial resulted in approval of Gleevec for GIST patients in the United States and other countries.

Blanke says PKC412 is “an inhibitor of protein kinase C, an enzyme important in cellular growth and division. It is less specific than Gleevec, inhibiting PKC, and kinases of KIT, VEGF, PDGF. Many of those kinases are important in GIST behavior.”

For patients to be eligible for the phase II Gleevec+PKC412 trial, Blanke said, they must have experienced disease progress while on 600 mg. Gleevec for at least two months.