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

This study is currently recruiting participants.
Verified January 2014 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Yoon-Koo Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01541709
First received: February 24, 2012
Last updated: January 13, 2014
Last verified: January 2014

February 24, 2012
January 13, 2014
March 2012
March 2016   (final data collection date for primary outcome measure)
progression-free survival (PFS) [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
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
progression-free survival (PFS) [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
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 version 1.0
Complete list of historical versions of study NCT01541709 on ClinicalTrials.gov Archive Site
  • disease control rate [ Time Frame: Up to 24weeks ] [ Designated as safety issue: No ]
  • safety control rate [ Time Frame: up to 24months ] [ Designated as safety issue: Yes ]
  • overall survival (OS) [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
  • imatinib PK(pharmacokinetics) (Cmin) [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
  • percentage of successful dose escalation [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
  • disease control rate [ Time Frame: Up to 24weeks ] [ Designated as safety issue: No ]
  • safety control rate [ Time Frame: up to 24months ] [ Designated as safety issue: Yes ]
  • overall survival (OS) [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
  • imatinib PK (Cmin) [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
  • percentage of successful dose escalation [ Time Frame: up to 24months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastrointestinal Stromal Tumors
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)
Experimental: Imatinib
Intervention: Drug: imatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
44
August 2016
March 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Yoon-Koo Kang, Md, PhD +82-2-3010-3230 ykkang@amc.seoul.kr
Contact: Min-Hee Ryu, MD, PhD +82-2-3010-5935 miniryu@amc.seoul.kr
Korea, Republic of
 
NCT01541709
CSTI571BKR24T
No
Yoon-Koo Kang, Asan Medical Center
Asan Medical Center
Not Provided
Principal Investigator: Yoon-Koo Kang, MD, PhD Asan Medical Center
Asan Medical Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP