Sorafenib in Combination With RAD001 in Advanced Solid Tumors Selected on Molecular Targets
Status:
Suspended
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Sorafenib is an oral multikinase inhibitor and among its targets are several RTKs involved in
tumor genesis (Raf, Flt-3, c-Kit and RET) and angiogenesis (VEGFR1, 2 and 3 and PDGFRß).
Therefore sorafenib inhibits tumor growth by a dual mechanism, acting either directly on the
tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through
inhibition of VEGFR and PDGFR signaling.
RAD001 is a novel derivative of rapamycin. It selectively inhibits mTOR directly blocking
tumor cells by preventing tumor cell growth and proliferation and indirectly by inhibiting
angiogenesis (via potent inhibition of the HIF-1 and consequently VEGF production).
Targeting mTOR in combination with sorafenib might lead to more profound effects on tumor
cell biology than could be achieved through individual targeting of some proteins.
New drugs have often met only limited success since not always target pathways responsible
for tumor development and growth are targeted. To overcome this problem, the specific
pathways targeted by the investigators two drugs will be analyzed in each single patient
before the inclusion.