Dovitinib for Imatinib/Sumitinib-failed Gastrointestinal Stromal Tumors (GIST): TKI258

Inclusion criteria

• 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 version 3.0
• 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

Exclusion criteria

• 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 abnormality.
• 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