Clinical trial NCT01541709: Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: KENEDI
Official title: A Phase II Study of Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: Imatinib Dose Escalation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Keywords: This is a single-center
prospective
single-arm
open-label phase II study
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2012-03-01
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: KIT exon 9 mutants had poorer survival compared with KIT exon 11 mutants when they were treated with the same dose of imatinib, 400 mg per day, and that patients with KIT exon 9 mutation had better progression-free survival with imatinib treatment at an escalated dose, 800 mg per day, than with imatinib treatment at a dose of 400 mg per day.10,11 Based on the results, imatinib 800 mg per day is now considered the standard dose for the treatment of patients with metastatic or unresectable GIST showing KIT exon 9 mutation in Western countries.

Detailed description: According to our previous prospective phase II study of imatinib 400 mg per day in metastatic or unresectable GIST, hematologic and non-hematologic toxicities were more frequent in Korean patients compared to the Western studies.7 It may be caused by relatively higher exposure to imatinib per body surface area in Korean patients than in Western population because the weight and height of Korean patients are relatively smaller than Western people. So, we plan to start imatinib at 400 mg per day and then sequentially escalate the doses of imatinib in this study.

Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Histologically confirmed metastatic or unresectable GIST with CD117(+), DOG-1 (+), or KIT mutation
* ECOG PS(Eastern Cooperative Oncology Group Performance Status) 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(radiofrequency ablation), 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

Primary outcomes:
measure: progression-free survival (PFS)
timeFrame: up to 24months
Secondary outcomes:
measure: disease control rate
timeFrame: Up to 24weeks
measure: safety control rate
timeFrame: up to 24months
measure: overall survival (OS)
timeFrame: up to 24months
measure: imatinib PK(pharmacokinetics) (Cmin)
timeFrame: up to 24months
measure: percentage of successful dose escalation
timeFrame: up to 24months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
Study officials:
affiliation: Asan Medical Center
name: Min-Hee Ryu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: