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
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumors
Drug: imatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 44
Study Start Date: March 2012
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01541709

Contacts
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

Locations
Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine Recruiting
Seoul, Korea, Republic of, 138-736
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   
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Yoon-Koo Kang, MD, PhD Asan Medical Center
  More Information

No publications provided

Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01541709     History of Changes
Other Study ID Numbers: CSTI571BKR24T
Study First Received: February 24, 2012
Last Updated: January 13, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
This is a single-center
prospective
single-arm
open-label phase II study

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014