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

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Imatinib mesylate (Glivec)

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Goyang, Korea, Republic of
    • National Cancer Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Seoul Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year Relapse Free Survival Rate	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Overall Survival Rate		2 years
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.

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: January 17, 2006
• First Submitted That Met QC Criteria: January 17, 2006
• First Posted (Estimate): January 19, 2006

Study Record Updates

• Last Update Posted (Actual): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Imatinib; GIST; Adjuvant therapy; Kit mutation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: AMC0501; CSTI571BKR08