Clinical trial NCT00278876: Adjuvant Imatinib in High-risk Gastrointestinal Stromal Tumor (GIST) With C-kit Mutation
Official title: Phase II Study of Imatinib Mesylate as Adjuvant Treatment in High-relapse Risk Localized Gastrointestinal Stromal Tumors With C-kit Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Gastrointestinal Stromal Tumors
Keywords: GIST
Imatinib
Adjuvant therapy
Kit mutation
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2006-01-19
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 2-year Relapse Free Survival Rate
timeFrame: 2 years
Secondary outcomes:
measure: 2-year Overall Survival Rate
timeFrame: 2 years
measure: Toxicity Profile
timeFrame: Monitoring of adverse events will be continued for at least 28days following the last dose of study treatment, up to 3 years.
Other outcomes:
Locations:
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Samsung Medical Center
Study officials:
affiliation: Asan Medical Center
name: Yoon-Koo Kang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: