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

Sponsor
Asan Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT00278876
Collaborator
(none)
47
4
1
71
11.8
0.2

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Drug: Imatinib mesylate (Glivec)
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (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
Study Start Date :
Apr 1, 2005
Actual Primary Completion Date :
Aug 1, 2007
Actual Study Completion Date :
Mar 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: imatinib mesylate

patients receiving adjuvant imatinib mesylate

Drug: Imatinib mesylate (Glivec)
Imatinib mesylate 400mg/day per oral (day 1-28) every 4 weeks

Outcome Measures

Primary Outcome Measures

  1. 2-year Relapse Free Survival Rate [2 years]

Secondary Outcome Measures

  1. 2-year Overall Survival Rate [2 years]

  2. Toxicity Profile [Monitoring of adverse events will be continued for at least 28days following the last dose of study treatment, up to 3 years.]

    Number of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of adjuvant imatinib

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 National Cancer Center Goyang Korea, Republic of
2 Asan Medical Center Seoul Korea, Republic of
3 Seoul National University Hospital Seoul Korea, Republic of
4 Seoul Samsung Medical Center Seoul Korea, Republic of

Sponsors and Collaborators

  • Asan Medical Center

Investigators

  • Principal Investigator: Yoon-Koo Kang, M.D., Ph.D., Asan Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00278876
Other Study ID Numbers:
  • AMC0501
  • CSTI571BKR08
First Posted:
Jan 19, 2006
Last Update Posted:
Jan 7, 2020
Last Verified:
Jan 1, 2020
Keywords provided by Yoon-Koo Kang, Professor, Asan Medical Center
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Forty-eight patients were enrolled at four centers in South Korea between August 2005 and June 2007.
Pre-assignment Detail One patient was excluded from the study before treatment initiation because of metastatic disease.
Arm/Group Title Imatinib Mesylate
Arm/Group Description imatinib mesylate 400 mg daily for 2 years
Period Title: Overall Study
STARTED 47
COMPLETED 38
NOT COMPLETED 9

Baseline Characteristics

Arm/Group Title Imatinib Mesylate
Arm/Group Description patients receiving adjuvant imatinib mesylate
Overall Participants 47
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
35
74.5%
>=65 years
12
25.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
56.3
(10.0)
Sex: Female, Male (Count of Participants)
Female
23
48.9%
Male
24
51.1%
Region of Enrollment (participants) [Number]
Korea, Republic of
47
100%

Outcome Measures

1. Primary Outcome
Title 2-year Relapse Free Survival Rate
Description
Time Frame 2 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Imatinib Mesylate
Arm/Group Description patients receiving adjuvant imatinib mesylate Imatinib mesylate (Glivec): Imatinib mesylate 400mg/day per oral (day 1-28) every 4 weeks
Measure Participants 47
Number [percentage of participants]
93.6
199.1%
2. Secondary Outcome
Title 2-year Overall Survival Rate
Description
Time Frame 2 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Imatinib Mesylate
Arm/Group Description patients receiving adjuvant imatinib mesylate Imatinib mesylate (Glivec): Imatinib mesylate 400mg/day per oral (day 1-28) every 4 weeks
Measure Participants 47
Number [percentage of participants]
97.9
208.3%
3. Secondary Outcome
Title Toxicity Profile
Description Number of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of adjuvant imatinib
Time Frame Monitoring of adverse events will be continued for at least 28days following the last dose of study treatment, up to 3 years.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Imatinib Mesylate
Arm/Group Description patients receiving adjuvant imatinib mesylate Imatinib mesylate (Glivec): Imatinib mesylate 400mg/day per oral (day 1-28) every 4 weeks
Measure Participants 47
Number [participants]
47
100%

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group Title Imatinib Mesylate
Arm/Group Description patients receiving adjuvant imatinib mesylate Imatinib mesylate (Glivec): Imatinib mesylate 400mg/day per oral (day 1-28) every 4 weeks
All Cause Mortality
Imatinib Mesylate
Affected / at Risk (%) # Events
Total / (NaN)
Serious Adverse Events
Imatinib Mesylate
Affected / at Risk (%) # Events
Total 0/47 (0%)
Other (Not Including Serious) Adverse Events
Imatinib Mesylate
Affected / at Risk (%) # Events
Total 47/47 (100%)
Blood and lymphatic system disorders
Anemia 40/47 (85.1%)
Leukopenia 28/47 (59.6%)
Neutropenia 34/47 (72.3%)
Thrombocytopenia 17/47 (36.2%)
Gastrointestinal disorders
Anorexia 29/47 (61.7%)
Nausea 23/47 (48.9%)
Vomiting 17/47 (36.2%)
Constipation 5/47 (10.6%)
Diarrhea 26/47 (55.3%)
Dyspepsia 13/47 (27.7%)
General disorders
Asthenia 25/47 (53.2%)
Hepatobiliary disorders
Elevated aspartate aminotransferase 12/47 (25.5%)
Elevated alanine transferase 13/47 (27.7%)
Hyperbilirubinemia 14/47 (29.8%)
Musculoskeletal and connective tissue disorders
Edema 42/47 (89.4%)
Weight gain 10/47 (21.3%)
Psychiatric disorders
Insomnia 5/47 (10.6%)
Renal and urinary disorders
Azotemia 3/47 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough 14/47 (29.8%)
Skin and subcutaneous tissue disorders
Dermatitis 27/47 (57.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Yoon-Koo Kang
Organization Asan Medical Center
Phone +82-2-3010-3210
Email ykkang@amc.seoul.kr
Responsible Party:
Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00278876
Other Study ID Numbers:
  • AMC0501
  • CSTI571BKR08
First Posted:
Jan 19, 2006
Last Update Posted:
Jan 7, 2020
Last Verified:
Jan 1, 2020