Adjuvant Imatinib in High-risk Gastrointestinal Stromal Tumor (GIST) With C-kit Mutation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yoon-Koo Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00278876
First received: January 17, 2006
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

The presence of c-kit mutation is an independent poor prognostic factor for relapse in addition to large size (> 5 cm) and high mitotic rate (> 5/50 high power field [HPF]) in localized gastrointestinal stromal tumor (GIST) patients who underwent complete surgical resection. In addition, the localized GIST which had exon 11 c-kit mutation and features of high-risk for relapse according to National Institute of Health (NIH) consensus guideline (tumor size > 10 cm or mitotic count > 10/50 HPF) also have high-risk of relapse. Until recently, there has been no effective therapy for advanced, unresectable GISTs. However, a new agent, imatinib mesylate, has shown promise in the metastatic setting, and c-kit exon 11 mutation is the strongest prognostic factor for better response and survival. It is reasonable to try imatinib in an earlier and minimal residual status especially for patients at higher risk of relapse and a higher probability of response to imatinib.


Condition Intervention Phase
Sarcoma
Gastrointestinal Stromal Tumors
Drug: Imatinib mesylate (Glivec)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Imatinib Mesylate as Adjuvant Treatment in High-relapse Risk Localized Gastrointestinal Stromal Tumors With C-kit Mutation

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Relapse free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity profile (according to NCI CTCAE(Common Terminology Criteria for Adverse Events) version 3.0) [ Time Frame: Monitoring of adverse events will be contineud for at least 28days following the last dose of study treatment ] [ Designated as safety issue: Yes ]

Enrollment: 47
Study Start Date: April 2005
Study Completion Date: March 2011
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: imatinib mesylate
patients receiving adjuvant imatinib mesylate
Drug: Imatinib mesylate (Glivec)
Imatinib mesylate 400mg/day per oral (day 1-28) every 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven diagnosis of GIST, with positive immunostaining for KIT (CD117)
  • Tumor size > 5 cm and mitotic rate > 5/50HPF(High Power Field), or tumor size > 10 cm irrespective of mitotic rate, or mitotic rate > 10/50 HPF irrespective of tumor size.
  • Presence of mutation in exon 11 of c-kit gene.
  • Surgery performed from 3 weeks to 8 weeks before administration of Imatinib mesylate.
  • No evidence of residual macroscopic and microscopic disease after surgery.
  • Absence of distant metastases
  • No prior radiation therapy, no prior chemotherapy, no prior therapy with Imatinib mesylate, or any other molecular targeted or biological therapy.
  • Age 18 yrs or older
  • ECOG(Eastern Cooperative Oncology Group electrocorticogram) performance status = 0-2
  • No New York Heart Association (NYHA) Class 3~4 cardiac problems
  • Absence of severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal disease, uncontrolled liver disease, including chronic viral hepatitis judged at risk of reactivation, uncontrolled active infection, such as human immunodeficiency virus (HIV) infection, etc.).
  • No ongoing pregnancy or nursing..
  • No prior, or ongoing other malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or adequately treated cancer with eradicative intent for which the patient has been continuously disease-free for 5 years.
  • No use of coumarin derivatives at the time of treatment start.
  • Adequate liver function, as defined by a serum bilirubin < 1.5 x the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 IULN, obtained within 7 days prior to randomization.
  • Adequate renal function, as defined by a serum creatinine < 1.5 x IULN, obtained within 7 days prior to randomization.
  • Absolute neutrophil count (ANC) > 1.5 x 109/l and a platelet count > 100 x 109/l obtained within 7 days prior to randomization. Baseline hemoglobin > 9 g/dl (this may be achieved by transfusions if needed).
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00278876

Locations
Korea, Republic of
National Cancer Center
Goyang, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Seoul Samsung Medical Center
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Yoon-Koo Kang, M.D., Ph.D. Asan Medical Center
  More Information

No publications provided

Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00278876     History of Changes
Other Study ID Numbers: AMC-ONCGI-0501, CSTI571BKR08
Study First Received: January 17, 2006
Last Updated: April 17, 2013
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
GIST
Imatinib
Adjuvant therapy
Kit mutation

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Sarcoma
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System 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 August 01, 2014