Adjuvant Imatinib in High-risk Gastrointestinal Stromal Tumor (GIST) With C-kit Mutation
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 |
---|---|---|
|
Phase 2 |
Study Design
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
- 2-year Relapse Free Survival Rate [2 years]
Secondary Outcome Measures
- 2-year Overall Survival Rate [2 years]
- 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
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.- AMC0501
- CSTI571BKR08
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
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%
|
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%
|
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
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 |
ykkang@amc.seoul.kr |
- AMC0501
- CSTI571BKR08