At a glance
ClinicalIndex Comparison RecordStandardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T)
In Brief
A Phase 2 clinical trial evaluating dovitinib for Gastrointestinal Stromal Tumors. Completed, enrolled 30 participants across 1 site.
Detailed 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. .
Study Details
Timeline
Interventions
TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule