NCT01440959

Dovitinib for Imatinib/Sumitinib-failed Gastrointestinal Stromal Tumors (GIST): TKI258

A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

With discovery of KIT mutations and the advent of KIT tyrosine kinase inhibitor imatinib (GlivecTM, Novartis), there has been substantial improvement in overall survival in patients with advanced and/or metastatic gastrointestinal tumors (GIST). Recently, sunitinib (SuteneTM, Pfizer) showed activity as second-line therapy in GIST patients after failure with imatinib. However, virtually all patients will eventually progress or become intolerable after the first-line imatinib and the second-line sunitinib. Dovitinib (TKI258, Novartis) is a multi-kinase inhibitor. TKI258 is a potent inhibitor of the VEGFR 1, 2, and 3, FGFR1, 2 and 3, PDGFRβ, Kit, RET, TrkA, CSF 1R, and FLT3 with inhibitory concentration 50% (IC50s) of less than 40nM. Stem cell factor (SCF) also termed KIT ligand, or steel factor has been shown to modulate tumor angiogenesis. In cultured human endothelial cells and Kit expressing cancer cells, TKI258 inhibits VEGF- and SCF-stimulated mitogenesis. .

Detailed description

It is well known that KIT and PDGFR which can be inhibited by TKI258 have a crucial role in the development and proliferation of GIST, and in general FGFR has an important role in angiogenesis and tumor proliferation in many cancers. We assume that TKI258 can be also effective in patients with GIST. The objective of this study is to evaluate the safety and activity of TKI258 given as salvage treatment for GIST after failure to standard imatinib and sunitinib.

Conditions

• Gastrointestinal Stromal Tumors

Interventions

Type	Name	Description
DRUG	dovitinib	TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule

Timeline

• Start date: 2011-09-01
• Primary completion: 2013-03-01
• Completion: 2013-03-01
• First posted: 2011-09-27
• Last updated: 2020-01-18
• Results posted: 2014-03-03

Locations

1 site across 1 country: South Korea