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

Sarcoma Clinical Trial

Official title:

Phase II Study of Imatinib Mesylate as Adjuvant Treatment in High-relapse Risk Localized Gastrointestinal Stromal Tumors With C-kit Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00278876
• Other study ID #: AMC0501
• Secondary ID: CSTI571BKR08
• Status: Completed
• Phase: Phase 2
• Start date: April 2005
• Est. completion date: March 2011

Study information

• Verified date: January 2020
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: March 2011
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors
• Sarcoma

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year Relapse Free Survival Rate		2 years
Secondary	2-year Overall Survival Rate		2 years
Secondary	Toxicity Profile	Number of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of adjuvant imatinib	Monitoring of adverse events will be continued for at least 28days following the last dose of study treatment, up to 3 years.