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

• ClinicalTrials.gov Identifier: NCT00278876
• Recruitment Status: Completed
• First Posted: January 19, 2006
• Results First Posted: July 27, 2015
• Last Update Posted: January 7, 2020
• Sponsor: Asan Medical Center
• Information provided by (Responsible Party): Yoon-Koo Kang, Asan Medical Center

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
Sarcoma; Gastrointestinal Stromal Tumors	Drug: Imatinib mesylate (Glivec)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: April 2005
• Actual Primary Completion Date: August 2007
• Actual Study Completion Date: March 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 [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. 2-year Overall Survival Rate [ Time Frame: 2 years ]
2. Toxicity Profile [ Time Frame: 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

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

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

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, Korea, Republic of

Sponsors and Collaborators

Asan Medical Center

Investigators

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

More Information

• Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT00278876
• Other Study ID Numbers: AMC0501; CSTI571BKR08
• First Posted: January 19, 2006
• Results First Posted: July 27, 2015
• Last Update Posted: January 7, 2020
• Last Verified: January 2020

Keywords provided by Yoon-Koo Kang, Asan Medical Center:

GIST; Imatinib; Adjuvant therapy; Kit mutation

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Imatinib Mesylate; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action