Rivoceranib Plus Paclitaxel in Patients With Gastrointestinal Stromal Tumor

Summary

The purpose of this study is to evaluate the efficacy and safety of rivoceranib and paclitaxel combination therapy in patients with P-glycoprotein overexpressing GIST who failed standard treatment with imatinib, sunitinib, and regorafenib.

Eligibility

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

Conditions2

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