NCT01226056

Sorafenib in Combination With RAD001 in Advanced Solid Tumors Selected on Molecular Targets

Phase I/II Trial With Sorafenib in Combination With RAD001 Administered Orally in Patients With Advanced Solid Tumors, Selected on the Base of Molecular Targets

• Status: Suspended
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Southern Europe New Drug Organization · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Advanced Solid Tumors

Interventions

Type	Name	Description
DRUG	RAD001 in combination with sorafenib	Phase I / Dose escalation: during the first cycle RAD001 (2.5-10 mg/day) will be administered alone, once a day, on days 1-14 to allow PK-profiling of the drug. From day 15 sorafenib administration (400-800 mg/day) twice a day will be added. The cycle 1 will last 6 weeks, subsequent cycles will last 4 weeks (the 2 drugs administered in combination from day 1 to day 28). Phase II: The drugs will be administered at the Recommended Dose and each treatment cycle will last 4 weeks.

Timeline

• Start date: 2009-03-01
• Primary completion: 2012-09-01
• Completion: 2012-12-01
• First posted: 2010-10-21
• Last updated: 2010-10-21

Locations

1 site across 1 country: Italy