A Phase II Study of Oral Paclitaxel (Liporaxel) in GIST Patients With a Low P-glycoprotein Expression After Failure With Imatinib, Sunitinib and Regorafenib
The purpose of this study is to evaluate safety and efficacy of Liporaxel for patients with GIST who failed on prior standard treatments, including imatinib, sunitinib, and regorafenib, and with low P-glycoprotein expression.
• Age 20 years or older, at the time of acquisition of informed consent
• Histologically confirmed metastatic and/or advanced GIST with CD117(+), DOG-1(+), or mutation in KIT or PDGFRα gene
• Failed (progressed and/or intolerable) after prior treatments for GIST, including at least imatinib and sunitinib, regorafenib.
• Adequate tissue obtained after treatment failure to imatinib, sunitinib, and regorafenib for P-glycoprotein immunohistochemistry (IHC) analysis, and showed P-glycoprotein expression of less than 6. (For patients with PDGFRα D842V mutation or other subtypes with poor response to tyrosine kinase inhibitors, tumor tissue obtained at any period can be used.)
• Eastern Cooperative Oncology Group (ECOG) performance status 0\
∙ 2
• Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0
• At least one measurable lesion as defined by RECIST version 1.1.
• Adequate bone marrow, hepatic, renal, and other organ functions
‣ Neutrophil \>1,500/mm3
⁃ Platelet \> 100,000/mm3
⁃ Hemoglobin \>8.0 g/dL
⁃ Total bilirubin \< 1.5 x upper limit of normal (ULN)
⁃ AST/ALT \< 2.5 x ULN
⁃ Creatinine \<1.5 x ULN
• Life expectancy \> 12 weeks
⁃ Washout period of previous TKIs or chemotherapy for more than 4 times the half life ((Imatinib and regorafenib need 1 week and sunitinib need 2 weeks.)
⁃ Provision of a signed written informed consent