Combination of rivoceranib and paclitaxel for advanced gastrointestinal stromal tumors

Inclusion Criteria:

* 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
* P-glycoprotin IHC score \> 3 (Tumor tissue with disease progression after regorafenib treatment)
* Failed (progressed and/or intolerable) after prior treatments for GIST, including at least imatinib and sunitinib, regorafenib.
* 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 ((Imitinib and regorafenib need 1 week and sunitinib need 2 weeks.)
* Provision of a signed written informed consent

Exclusion Criteria:

* Women of child-bearing potential who are pregnant or breast feeding
* Women or men who are not willing to use effective contraception entering the study period or until at least 3 months after the last study drug administration.
* If any of the following applies within ≤ 6 months prior to starting study enrollment : Myocardial Infarction, severe instable angina, coronary/peripheral bypass, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack, treatment required severe arrhythmia.
* Uncontrolled infection
* Acute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligible)
* Uncontrolled gastrointestinal toxicities with toxicity greater than NCI CTCAE grade 2
* Acute, or chronic medical or psychiatric condition or laboratory abnormality such as active uncontrolled infection that difficult to study participation in the judgment of the investigator
* The patient experienced any bleeding episode considered life-threatening, or any grade 3 or 4 bleedig event. (required transfusion or endoscopic or surgical intervention)
* Currently clinically significant (within 7 days prior to screening) treatment of anticoagulants or other thrombolytic agents. A maximum dose of 325 mg/day of aspirin is allowed
* History of uncontrolled hypertension (blood pressure ≥140/90 mmHg and change in antihypertensive medication within 7 days prior to screening) that is not well managed by medication and the risk of which may be precipitated by a VEGF inhibitor therapy.
* History of clinically serious opearation, bone fracture or non-healing wounds within the last 3 weeks prior to screening
* History of other significant cardiovascular diseases or vascular diseases, within the last 6 months prior to screening (e.g., hypertensive crisis, and hypertensive encephalopathy or transient ischemic attack or significant peripheral vascular diseases\] that, in the investigator's opinion, may pose a risk to the patient on VEGFR inhibitor therapy.
* History of clinically significant glomerulonephritis, biopsy-proven tubulointerstitial nephritis, crystal nephropathy, or other renal insufficiencies
* Known diagnosis of HIV infection (HIV testing is not mandatory).
* History of another primary malignancy that is currently clinically significant or currently requires active intervention.
* Patients with clinically suspected brain metastasis symptom, brain metastases as assessed by radiologic imaging
* Alcohol or substance abuse disorder.
* Known hypersensitivity to rivoceranib or any component of its formulation or history of severe hypersensitivity to including Cremophor R EL(polyoxyethylated castor oil) drug
* Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19
* Active bacterial infections