Rivoceranib Plus Paclitaxel in Patients With Gastrointestinal Stromal Tumor

• Status: Not yet recruiting
• Trial end date: 2026-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Treatments: Apatinib; Paclitaxel

Criteria

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