A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T)
- Age 20 years or older
- 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 both imatinib and sunitinib .
- ECOG performance status of 0~2
- Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE
- At least one measurable lesion as defined by RECIST version 1.0.
- Adequate bone marrow, hepatic, renal, and other organ functions
- Neutrophil > 1,500/mm3
- Platelet > 75,000/mm3
- Hemoglobin > 8.0 g/dL
- Total bilirubin < 1.5 x upper limit of normal (ULN)
- AST/ALT < 2.5 x ULN (or < 5 x ULM in case of liver metastases)
- Creatinine < 1.5 x ULN
- Amylase, lipase < ULN
- Electrolytes should be within normal limits.
- Urine dipstick reading: Negative for proteinuria or, if documentation of +1 results
for protein on dipstick reading, then total urinary protein ≤ 500 mg and measured
creatinine clearance ≥ 50 mL/min/1.73m2 from a 24-hour urine collection
- Life expectancy > 12 weeks
- Women with reproductive potential must have a negative serum or urine pregnancy test
- Washout period of previous TKIs or chemotherapy for more than 4 times the half life.
- Provision of a signed written informed consent
- Women of child-bearing potential who are pregnant or breast feeding or adults of
reproductive potential not employing an effective method of birth control.
- Clinically significant cardiac disease (New York Heart Association, Class III or IV)
or impaired cardiac function or clinically significant cardiac diseases,
- Uncontrolled infection.
- Diabetes mellitus (insulin dependent or independent disease, requiring chronic
medication) with signs of clinically significant peripheral vascular disease.
- Previous pericarditis; clinically significant pleural effusion in the previous months
or current ascites requiring two or more interventions/month.
- Known pre-existing clinically significant disorder of the hypothalamic-pituitary
axis, adrenal or thyroid glands.
- Prior acute or chronic pancreatitis of any etiology.
- Acute and chronic liver disease and all chronic liver impairment.
- Malabsorption syndrome or uncontrolled gastrointestinal toxicities with toxicity
greater than NCI CTCAE grade 2.
- Other severe, acute, or chronic medical or psychiatric condition or laboratory
- Treatment with any of the medications that have a potential risk of prolonging the QT
interval or inducing Torsades de Points and the treatment cannot be discontinued or
switched to a different medication prior to starting study drug.
- Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, rifampin, phenytoin
and quinidine 2 weeks prior baseline.
- Major surgery ≤ 28 days prior to starting study drug or who have not recovered from
side effects of such therapy.
- Known diagnosis of HIV infection .
- History of another primary malignancy that is currently clinically significant or
currently requires active intervention.
- Patients with brain metastases as assessed by radiologic imaging
- Alcohol or substance abuse disorder.
- no other inhibitor of FGFR except sunitinib