Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation

Inclusion Criteria:

• Age 18 or older
• Histologically confirmed metastatic or unresectable GIST with CD117(+), DOG-1 (+), or KIT mutation
• ECOG PS 0~2
• Primary mutation at KIT exon 9
• Imatinib treatment for less than 4 weeks from the first dose at 400 mg per day
• No prior use of tyrosine kinase inhibitors ((but, patients who have recurrence 6 months after completion of adjuvant imatinib at a dose of 400 mg per day can be enrolled in this study)
• At least one evaluable disease by RECIST v1.0
• Resolution of all toxic effects of prior treatments (chemotherapy, surgery, RFA, radiotherapy, and/or TACE)
• Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L (within 1 week prior to the first dose of imatinib at 400 mg per day)
• Adequate renal function, with serum creatinine < 1.5 x ULN (within 1 week prior to the first dose of imatinib at 400 mg per day)
• Adequate hepatic function with serum total bilirubin < 1.5 x ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN in the absence of liver metastases, or < 5 x UNL in the presence of liver metastases (within 1 week prior to the first dose of imatinib at 400 mg per day)
• No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse
• Provision of a signed written informed consent

Exclusion Criteria:

• Severe co-morbid illness and/or active infections
• Pregnant or lactating women
• History of other malignancies except basal cell carcinoma and carcinoma in situ of uterine cervix
• CNS metastasis
• Clinically significant bleeding in GI tract
• GI obstruction or malabsorption
• Known hypersensitivity to imatinib