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

Sponsor

Asan Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01541709

Collaborator

(none)

Enrollment

Location

Arm

117

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: imatinib	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Imatinib	Drug: imatinib The patients will receive 400 mg per day of imatinib for 4 weeks, and then 600mg per day (300 mg po bid) for 4 weeks if tolerable to 400 mg per day, and then 800 mg per day (400 mg po bid)

Arm

Intervention/Treatment

Experimental: Imatinib

Drug: imatinib

The patients will receive 400 mg per day of imatinib for 4 weeks, and then 600mg per day (300 mg po bid) for 4 weeks if tolerable to 400 mg per day, and then 800 mg per day (400 mg po bid)

Outcome Measures

Primary Outcome Measures

progression-free survival (PFS) [up to 24months]
evaluated with Triphasic or dynamic CT scans of abdomen & pelvis, and other involved sites. Follow-up CT scans will be performed at 4 weeks and 12 weeks after the first dose of imatinib at 400 mg per day, and then every 3 months until disease using RECIST(Response Evaluation Criteria in Solid Tumors) version 1.0

Secondary Outcome Measures

disease control rate [Up to 24weeks]
safety control rate [up to 24months]
overall survival (OS) [up to 24months]
imatinib PK(pharmacokinetics) (Cmin) [up to 24months]
percentage of successful dose escalation [up to 24months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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