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

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ClinicalTrials.gov Identifier: NCT01541709
Recruitment Status : Recruiting
First Posted : March 1, 2012
Last Update Posted : July 14, 2017
Sponsor:
Information provided by (Responsible Party):
Yoon-Koo Kang, Asan Medical Center

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
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
Actual Study Start Date : March 2012
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017


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)



Primary Outcome Measures :
  1. progression-free survival (PFS) [ Time Frame: 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 :
  1. disease control rate [ Time Frame: Up to 24weeks ]
  2. safety control rate [ Time Frame: up to 24months ]
  3. overall survival (OS) [ Time Frame: up to 24months ]
  4. imatinib PK(pharmacokinetics) (Cmin) [ Time Frame: up to 24months ]
  5. percentage of successful dose escalation [ Time Frame: up to 24months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01541709     History of Changes
Other Study ID Numbers: CSTI571BKR24T
First Posted: March 1, 2012    Key Record Dates
Last Update Posted: July 14, 2017
Last Verified: July 2017

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

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action